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340 Study Matches
Congenital Hemolytic and Dyserythropoietic Anemias
Megan Metcalf - megan.metcalf@cchmc.org
ALL
NCT07649213
Inclusion Criteria:
• Patients who have been diagnosed, by medical history and review of the laboratory data obtained for clinical care, including CBC/reticulocyte count and review of the blood smear, with a hereditary hemolytic anemia, where the genetic etiology is challenging to be identified.
• Parents and/or grandparents of children that have the above diagnosis. The parents and/or grandparents may or may not have non-immune hemolytic anemia (these will serve as positive or negative inherent controls) Exclusion: 1\) Patients with anemias known to be acquired and not associated with a genetic etiology.
Hemolytic Anemia
Dichoptic Treatment for Amblyopia in Children 8 to 12 Years of Age (ATS24)
Jillian Bulman - jillian.bulman@cchmc.org
ALL
8 years to 12 years old
PHASE3
NCT06524882
Inclusion Criteria:
• Age 8 to \<13 years.
• VA, measured in each eye without cycloplegia in current refractive correction (if applicable) using the E-ETDRS VA protocol on a study-approved device displaying single surrounded optotypes, as follows:
• VA in the amblyopic eye 20/40 to 20/200 inclusive (33 to 72 letters with E-ETDRS).
• VA in the fellow eye 20/25 or better (≥ 78 letters with E-ETDRS).
• Interocular difference ≥ 3 logMAR lines (≥ 15 letters) i.e., amblyopic eye VA at least 3 logMAR lines worse than fellow eye VA).
• Amblyopia associated with strabismus, anisometropia, or both (previously treated or untreated).
• Criteria for strabismic amblyopia: At least one of the following must be met: * Presence of a heterotropia on examination at distance or near fixation (with optical correction), must be \<=5 prism diopters (∆) by SPCT at distance and near fixation. * Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia).
• Criteria for anisometropia: At least one of the following criteria must be met: * ≥1.00 D difference between eyes in spherical equivalent (SE). * ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes.
• Criteria for combined-mechanism: Both of the following criteria must be met: * A criterion for strabismus is met (see above). * ≥1.00 D difference between eyes in SE OR ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes.
• No more than 2 weeks (cumulative) of prior dichoptic treatment
• No treatment with cycloplegic eyedrops (e.g., atropine) in the past 2 weeks; other treatments allowed up to enrollment but then must be discontinued.
• Refractive correction is required (single vision lenses or contact lenses) for any of the following refractive errors based on a cycloplegic refraction completed within the last 7 months: * Hypermetropia of 2.50 D or more by SE * Myopia of amblyopic eye of 0.50D or more SE * Astigmatism of 1.00D or more * Anisometropia of more than 0.50D SE NOTE: Children with cycloplegic refractive errors that do not fall within the requirements above for refractive correction may be given refractive correction at investigator discretion but must follow the study-specified prescribing guidelines, as detailed below. NOTE: Monocular or binocular contact lens wear is allowed provided the contact lenses meet the refractive error correction requirements below. For each child, all testing must be performed using the same form of optical correction (i.e., no changing between contacts and spectacles).
• Spectacles/contact lens correction prescribing instructions referenced to the cycloplegic refraction completed within the last 7 months: * SE must be within 0.50D of fully correcting the anisometropia (if new glasses are prescribed, reduction in plus sphere must be symmetric in the two eyes). * SE must not be under corrected by more than 1.50D SE. * Cylinder power in both eyes must be within 0.50D of fully correcting the astigmatism. * Axis must be within +/- 10 degrees if cylinder power is ≤1.00D, and within +/- 5 degrees if cylinder power is \>1.00D. * Myopia must not be under corrected by more than 0.25D or over corrected by more than 0.50D SE, and any change must be symmetrical in the two eyes.
• Spectacles/contact lens correction (with or without other treatment such as patching) meeting the above criteria must be worn: * For at least 18 weeks OR until VA stability is documented (defined as \<1-line change by the same testing method measured on 2 consecutive exams at least 9 weeks apart). * For determining VA stability (non-improvement): * The first of two measurements may be made 1) in current correction, or 2) in trial frames with or without cycloplegia or 3) without correction (if new correction is prescribed), * The second measurement must be made without cycloplegia in the correct spectacles/contact lens correction that has been worn for at least 9 weeks. * NOTE: Because this determination is a pre-randomization, the method of measuring VA is not mandated.
• Participant is willing to wear a headset.
• Participant is willing to continue full-time spectacles/contact lens wear (if needed).
• Interpupillary distance of 52mm to 72mm inclusive.
• Investigator is willing to prescribe continued spectacles/contact lens correction (if needed) or either dichoptic device per protocol.
• Participant is willing to accept assignment to either continued spectacles/ contact lens wear alone, dichoptic movies/shows (view 1 hour per day 6 days per week) OR dichoptic games (play approximately 25 minutes per day, 6 days per week) for 19 weeks.
• Parent understands the protocol and is willing to accept randomization.
• Parent has phone (or access to phone) and is willing to be contacted by JAEB Center staff.
• Relocation outside of area of an active PEDIG site for this study within the next 36 weeks is not anticipated.
Exclusion Criteria:
• Heterotropia more than 5∆ at distance or near (measured by SPCT in current correction)
• Prism greater than a total of 8 diopters horizontal and 1 diopter vertical in the refractive correction at time of enrollment.
• Current bifocal spectacles (eligible only if bifocal discontinued 2 weeks prior to enrollment).
• Myopia greater than -6.00D spherical equivalent in either eye.
• Ocular co-morbidity that may reduce VA determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the participant if the above visual acuity criteria are met using patch occlusion. Fogging is not permitted).
• Diplopia more than once per week over the last week prior to enrollment by parental report.
• History of light-induced seizures.
• Known simulator sickness.
• Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities are not excluded.
• Immediate family member (biological or legal guardian, child, sibling, parent) of investigative site personnel directly affiliated with this study or an employee of the JAEB center for Health Research.
DEVICE: Vivid Vision, DEVICE: Luminopia, DEVICE: Optical Correction
Amblyopia
Dichoptic, Luminopia, Vivid Vision, Game, movie, glasses
Efficacy of Tezepelumab in Peanut Oral Immunotherapy (ZENITH)
Jenny Duncan - jenny.duncan@cchmc.org
ALL
12 years to 55 years old
PHASE2
NCT07015996
Inclusion Criteria:
• Participant and/or parent/legal guardian must be able to understand and provide informed consent (parental permission and informed assent of minor, if applicable).
• Age 12 to 55 years inclusive with a personal history of an allergic reaction to peanut ingestion
• A positive reaction at or below ingestion of 100 mg of peanut protein in a single dose (≤ 144 mg cumulative dose) during the Screening DBPCFC
• A negative challenge to the placebo (oat) during the Screening DBPCFC
• Sensitization to peanut as evidenced by either one of the following:
• positive sIgE to Ara h2 ≥ 0.35 kU/L by ImmunoCAPTM testing, or
• wheal ≥ 3 mm on skin prick test to peanut extract compared to a negative control
• Female participants of childbearing potential must have a negative pregnancy test upon study entry
• Female participants with reproductive potential must agree to use an FDA approved method of contraception for the duration of the study
• Willing and able to comply with the study protocol requirements
• Participants with other food allergies must agree to continue avoidance of these food items from their diet to avoid confounding the safety and efficacy data of the study
Exclusion Criteria:
• Currently in build-up phase of aeroallergen immunotherapy
• Current food allergen immunotherapy or use of any food allergen immunotherapy within the past 12 months
• Pregnant, planning a pregnancy during the study, or breast-feeding
• History of intolerance, hypersensitivity, or allergic reactions to tezepelumab, or the inactive ingredients (excipients) of tezepelumab, other IgG biologics, or rescue medications and their excipients
• Allergy to oat (participant reported)
• History of severe systemic allergic reaction to peanut with symptoms including the need for mechanical ventilation and/or severe hypotension requiring intensive care unit admission
• Asthma requiring high dose inhaled corticosteroid therapy for control (2007 NHLBI Criteria Steps 5 or 6 in adults and adolescents)
• History of a life-threatening asthma attack within 12 months prior to screening (e.g., requiring an ICU admission or intubation with mechanical ventilation), need for oral corticosteroids for asthma management within the last 6 months, or current Asthma Control Test score less than 19 at screening
• History of ischemic cardiovascular disease or other cardiac disease, which, in the opinion of the site investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
• History of eosinophilic gastrointestinal disease at screening
• History of disease affecting the immune system such as autoimmune disease (e.g., systemic lupus erythematosus), immune complex disease (e.g., serum sickness), or immunodeficiency, which, in the opinion of the site investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
• History of malignancy of any type, excluding basal cell and squamous cell cancers of the skin that only required surgical excision or in situ carcinoma of the cervix study provided that curative therapy was completed at least 12 months prior to screening
• Current known helminth infection
• Positive QuantiFERON - TB Gold test or TB Gold Plus, or T-SPOT® TB test unless the potential participant has been treated with appropriate chemoprophylaxis. In the case of an indeterminate or borderline Interferon Gamma Release Assay (IGRA), an IGRA may be repeated.
• Any of the following:
• HIV
• Current or prior infection with hepatitis B virus (HBV)
• Current or prior infection with hepatitis C virus (HCV), except adequately treated HCV with sustained virologic response ≥ 12 weeks.
• Active liver disease, defined as either:
• AST, ALT, and/or Alk phos \>2x ULN, or
• other active liver disease which, in the opinion of the site investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
• Any of the following:
• Current use of beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin-receptor blockers
• Received any investigational product within the past 4 months or 5 half-lives (whichever is longer) prior to screening
• Received systemic corticosteroids within 14 days prior to screening
• Receipt of immunoglobulin or other blood product within 30 days prior to screening
• Receipt of live attenuated vaccine within 30 days prior to screening
• Use of an immunosuppressant or immunomodulating drug within 30 days prior to screening
• Use of biologics targeting the human immune system within the past 12 months prior to screening
• Use of any herbal medications, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
• Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the site investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study
BIOLOGICAL: Tezepelumab, DRUG: Peanut Oral Immunotherapy (OIT), BIOLOGICAL: Placebo for Tezepelumab
Peanut Allergy
Tezepelumab, Peanut, Oral Immunotherapy
Phase 1 Study of INBRX-109 in Subjects With Locally Advanced or Metastatic Solid Tumors Including Sarcomas
- cancer@cchmc.org
ALL
12 years to 85 years old
PHASE1
NCT03715933
Inclusion Criteria:
• Males or females aged ≥12 to less than 85 years for Ewing sarcoma and 18 to less than 85 years of age for other tumors.
• Part 3 combination therapy expansion tumor types: * Histologically confirmed Ewing sarcoma with a classical fusion: Patients with locally advanced or metastatic, unresectable, relapsed, or refractory disease who have received at least 1 but no more than 2 prior lines of systemic treatment with a preferred first line chemotherapy regimens. * Colorectal adenocarcinoma: Patients who have failed 1 (one) prior line of systemic therapy that did not include irinotecan. * Colorectal adenocarcinoma: Patients who have failed 2 but no more than 3 prior lines of systemic therapy and are FTD/TPI-naïve.
• Measurable disease as defined by RECISTv1.1 (or modified RECIST for mesothelioma) criteria.
• Adequate hematologic, coagulation, hepatic and renal function as defined per protocol.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) score of 0 or 1, or Karnofsky Performance Status score of ≥60, or Lansky Play-Performance Scale for Children score ≥60 (for patients less than 16 years).
• Estimated life expectancy of at least 12 weeks.
• Availability of archival tissue or fresh cancer biopsy are mandatory.
Exclusion Criteria:
• Prior treatment with or exposure to DR5 agonists.
• Receipt of any anticancer therapy (including investigational agents) within 4 weeks or within 5 half-lives prior to the first dose of study treatment. Exceptions per protocol.
• Allergy or sensitivity to INBRX-109 or known allergies to CHO-produced antibodies.
• Receipt of radiotherapy within 4 weeks prior to the first dose of study treatment, and liver-directed within 12 months prior to the first dose of study drug.
• Subject has undergone allogeneic hematopoietic stem cell or bone marrow transplantation within the last 5 years. Exceptions per protocol.
• Prior or concurrent malignancies. Exceptions per protocol.
• Hematologic malignancies.
• Symptomatic active primary CNS tumors, leptomeningeal disease, and CNS metastases. Exceptions per protocol. Patients with any evidence or history of multiple sclerosis (MS) or other demyelinating disorders are excluded.
• Chronic liver diseases including fatty liver. Exception: Patients \< 45 years old with fatty liver disease may be accepted as long as adequate hepatic function as defined in the inclusion/exclusion criteria is confirmed.
• Acute viral or toxic liver disease within 12 months prior to the first dose of study drug.
• Evidence or history of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
• Known sensitivity or contraindications to the following drugs: * Ewing sarcoma: irinotecan or TMZ * colorectal adenocarcinoma: FU, leucovorin, irinotecan, bevacizumab or FTP/TPI
• Clinically significant cardiac condition, including myocardial infarction, uncontrolled angina, cerebrovascular accident, or other acute uncontrolled heart disease less than 3 months prior to enrollment.
• Acute, hemodynamically significant deep vein thrombosis or clinically significant pulmonary embolism not resolved or stable for at least 3 months prior to the start of study treatment.
• Major surgery within 4 weeks prior to enrollment on this trial.
• Systemic infection requiring antibiotics within 2 weeks prior to the first dose of study drug.
• Other exclusion criteria per protocol.
DRUG: INBRX-109, DRUG: Irinotecan, DRUG: Temozolomide, DRUG: carboplatin, DRUG: pemetrexed, DRUG: Leucovorin, DRUG: Fluorouracil, DRUG: Bevacizumab, DRUG: Trifluridine + Tipiracil
Ewing Sarcoma, Colorectal Adenocarcinoma
Phase 1, Phase 1 Clinical Trial, Solid Tumors, Sarcoma, DR5, Ewing Sarcoma, CRC, colorectal adenocarcinoma
A Randomized Trial to Evaluate Sequential vs Simultaneous Patching (ATS22)
Shipra Rai - shipra.rai2@cchmc.org
ALL
3 years to 13 years old
PHASE3
NCT04378790
Inclusion Criteria:
• Age 3 to \<13 years at the time of randomization
• Amblyopia associated with anisometropia, strabismus, or both o Criteria for strabismic amblyopia: At least one of the following must be met: * Presence of a heterotropia on examination at distance or near fixation (with or without optical correction) * Documented history of strabismus which is no longer present (which in the judgment of the investigator could have caused amblyopia) * Criteria for anisometropia: At least one of the following criteria must be met: * 1.00 D difference between eyes in spherical equivalent (SE) * 1.50 D difference in astigmatism between corresponding meridians in the two eyes * Criteria for combined-mechanism amblyopia: Both of the following criteria must be met: * Criteria for strabismus are met (see above) * 1.00 D difference between eyes in spherical equivalent OR ≥1.50 D difference in astigmatism between corresponding meridians in the two eyes
• No previous treatment for amblyopia, including no more than 24 hours of spectacle wear.
• Investigator planning to initiate spectacle correction of refractive error meeting the following criteria based on a cycloplegic refraction that has been performed within 30 days:
• Full correction of anisometropia
• Full correction of astigmatism with the same axis found by the cycloplegic refraction
• Full correction of any myopia
• Hyperopia must not be under corrected by more than 1.50 D, and reduction in plus sphere must be symmetric in the two eyes.
• At enrollment, single VA measured in each eye assessed in trial frames with the spectacle correction the investigator plans to prescribe, using the investigator's routine method as follows: * VA in the amblyopic eye 20/40 to 20/200 inclusive. * Age-normal VA in the fellow eye:40,41 * 3 years: 0.4 logMAR (20/50) or better * 4 years: 0.3 logMAR (20/40) or better * 5-6 years: 0.2 logMAR (20/32) or better * 7-12 years: 0.12 logMAR (78 letters) or better * Interocular difference ≥ 3 logMAR lines (0.3 logMAR) or ≥ 15 letters o When participants return for the Spectacle Baseline / Randomization Visit with their new spectacles, they will need to meet the same criteria as above using the ATS-HOTV or E-ETDRS protocol after wearing the new spectacles for at least 10 minutes (based upon the mean of a test and retest of VA in those new spectacles).
• Investigator is willing to prescribe spectacle wear followed sequentially by patching or simultaneous spectacles and patching treatment per protocol.
• Parent understands the protocol and is willing to accept randomization.
• Parent has phone (or access to phone) and is willing to be contacted by Jaeb Center staff or other study staff.
• Relocation outside of area of an active PEDIG site for this study within the next 56 weeks is not anticipated.
Exclusion Criteria:
• Myopia greater than -6.00 D spherical equivalent in either eye.
• Previous intraocular or refractive surgery.
• Planned strabismus surgery in the next 56 weeks.
• Any previous treatment for amblyopia (patching, atropine, Bangerter filter, vision therapy, or binocular treatment).
• Previous spectacle or contact lens wear for more than 24 hours.
• Parent and participant willing to forego option of contact lens wear for the duration of the study.
• Ocular co-morbidity that may reduce VA determined by an ocular examination performed within the past 7 months (Note: nystagmus per se does not exclude the participant if the above VA criteria are met).
• Severe developmental delay that would interfere with treatment or evaluation (in the opinion of the investigator). Participants with mild speech delay or reading and/or learning disabilities or attention deficit hyperactivity disorder (ADHD) are not excluded.
• Known allergy to adhesive patches.
• Known allergy to silicone.
OTHER: Patching, OTHER: Glasses
Amblyopia
patching, glasses, spectacles, simultaneous, sequential
Efficacy, Safety, and Pharmacokinetics of Vericiguat in Pediatric Participants With Heart Failure Due to Left Ventricular Systolic Dysfunction (MK-1242-036)
Sarah Speed - sarah.speed@cchmc.org
ALL
29 days to 17 years old
PHASE2
NCT05714085
Inclusion Criteria:
* Has symptomatic chronic heart failure (HF) resulting from systemic left ventricular (LV) systolic dysfunction.
* Has biventricular physiology with a morphologic systemic left ventricle.
* Is currently receiving stable medical therapy for HF.
* Has left ventricular ejection fraction (LVEF) \<45% assessed within 3 months before randomization.
* Is of any sex/gender, from \>28 days to \<18 years of age inclusive. Must weigh ≥3 kg to participate.
* Female is eligible to participate if not pregnant or breastfeeding, and at least one of the following: is not a participant of childbearing potential (POCBP); or is a POCBP who uses a highly effective contraceptive method; has a negative highly sensitive pregnancy test; abstains from breastfeeding during the study intervention period and for at least 30 days after study intervention; and their medical history; their menstrual history, and recent sexual activity has been reviewed.
* Extension Period: Was randomized, received at least 1 dose of study intervention (vericiguat or placebo), did not permanently discontinue study intervention, and completed the Week 52 visit and safety follow-up period of the Base Period
Exclusion Criteria:
* Is clinically unstable-with at least one of the following: has symptomatic hypotension or is hypotensive for age, recent use of intravenous (IV) inotrope and/or IV vasodilator, or recent IV diuretic.
* Has a known allergy or sensitivity to vericiguat, any of its constituents, or any other soluble guanylate cyclase (sGC) stimulator.
* Has a history of single ventricle heart disease or has a morphologic systemic right ventricle.
* Has undergone heart transplantation, is awaiting heart transplantation United Network for Organ Sharing (UNOS) Class 1A or equivalent, is receiving continuous IV infusion of an inotrope, or has an implanted ventricular assist device.
* Has sustained or symptomatic dysrhythmia uncontrolled with drug or device therapy.
* Has had recent cardiovascular (CV) surgical procedure or percutaneous intervention to palliate or correct congenital CV malformations.
* Has unoperated or residual hemodynamically significant congenital cardiac malformations.
* Has hypertrophic or restrictive cardiomyopathy.
* Has active myocarditis or has been recently diagnosed with presumed or definitive myocarditis.
* Has acute coronary syndrome, undergone recent coronary intervention, or indication for coronary revascularization.
* Has symptomatic carotid stenosis or other symptomatic cerebrovascular disease
* Has severe pulmonary hypertension.
* Requires continuous home oxygen for significant pulmonary disease and/or has known interstitial lung disease.
* Has severe chronic kidney disease.
* Has hepatic disorder such as hepatic encephalopathy, hepatic laboratory abnormalities or Child Pugh Class C.
* Has a gastrointestinal or biliary disorder that could impair absorption, metabolism, or excretion of medications.
* Has significant bone disease (other than osteopenia) that in the assessment of the investigator can alter bone formation
* Has concurrent or anticipated concomitant use of phosphodiesterase type 5 inhibitors or an sGC stimulator.
* Has received a COVID-19 vaccination within 1 week before randomization. DRUG: Vericiguat tablet, DRUG: Vericiguat suspension, DRUG: Placebo tablet, DRUG: Placebo suspension
Heart Failure, Left Ventricular Systolic Dysfunction
Extended vs Short-term Abatacept Dosing for Graft Versus Host Disease Prophylaxis (ABA3)
Celeste Dourson - Celeste.Dourson@cchmc.org
ALL
2 years and over
PHASE2
NCT04380740
Inclusion Criteria:
• Must be at least 2 years old and weigh 10 kg.
• Must have a willing unrelated adult donor (bone marrow or peripheral blood). Donors may have a single mismatch (i.e. be a 7/8) and this mismatch may be at the allele or antigen level; however, donors with allele level disparity should be given preference over those with antigen level disparity. Patients for whom a donor is available with disparity only in the host versus graft direction (because of recipient homozygosity), will not be eligible, since this mismatching does not increase the risk for GVHD. Centers may perform extended typing (e.g. DQB1 and DPB1) according to institutional practices and use these results in selecting donors; however, it is recommended that this extending typing be used only to select between donors who are equally well matched with the recipient at the A, B, C and DRB1.
• All patients and/or their parents or legal guardians must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
• Must have a hematologic malignancy treatable by HCT (except for those stipulated below under study Exclusion Criteria), which is in remission by standard testing (no patients in relapse will be included).
• Patients with an inherited predisposition to leukemia or otherwise hematologic malignancies that have not been associated with predisposition to transplant morbidities or non-hematologic cancers.
• Karnofsky performance score or Lanskey Play-Performance Scale score \>/= 80. * If the patient does not meet defined eligibility requirements, the PI/study committee must be contacted to determine eligibility.
Exclusion Criteria:
• Patients with the following hematologic malignancies will be excluded: Chronic Lymphocytic Leukemia, Myeloma and Primary Myelofibrosis.
• Active Relapse (\>5% blasts) of their primary malignancy.
• For patients with Acute Lymphocytic Leukemia (ALL) with pre-transplant MRD testing performed as standard practice at the treating institution, patients with MRD \>0.01% will be ineligible.
• For patients with Acute Myeloid Leukemia (AML) with pre-transplant MRD testing as standard of practice at the treating institution, patients with any MRD status are eligible and should be enrolled at the discretion of provider.
• For patients with MDS, those with \>5% blasts will be excluded.
• Prior allogeneic HCT.
• Uncontrolled viral, bacterial, fungal or protozoal infection at the time of study enrollment.
• HIV infection.
• Serious psychiatric disease including schizophrenia, bipolar disorder and severe depression.
• Prisoners or others who are compulsorily detained.
• Any patient with a known or suspected inherited predisposition to cancer should be discussed with the study team prior to screening for eligibility.
• Patients with a known inherited or constitutional predisposition to transplant morbidities, including, but not limited to Fanconi Anemia, Dyskeratosis Congenita, Shwachman-Diamond Syndrome and Down Syndrome will be excluded.
• Patients with known inherited or constitutional predisposition to non-hematologic cancers including, but not limited to Li-Fraumeni syndrome, BRCA1 and BRCA2 mutations will be excluded.
• Patients with active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, and are disease free for \<2 years.
• Incompletely treated active tuberculosis Infection.
• Pregnancy (positive serum b-HCG) or breastfeeding.
• Estimated GFR of \< 50 mL/min/1.73m2.
• Cardiac ejection fraction \< 50 (using M-Mode if assessment is done by ECHO)
• T.bilirubin \> 2 × upper limit of normal or ALT \> 4 × upper limit of normal or unresolved veno-occlusive disease.
• Pulmonary disease with FVC, FEV1 or DLCO parameters \<45% predicted (corrected for hemoglobin) or requiring supplemental oxygen. Children who are developmentally unable to perform pulmonary function testing will be assessed solely on their need for supplemental oxygen.
• Presence of antibodies to a mismatched donor HLA antigen (please refer to Section 3.4.g).
• Patients who have developed severe AGVHD, severe CGVHD or relapse will be excluded at the time of randomization.
• Exclusion Criteria Prior to Randomization (prior to 5th dose of abatacept/placebo):
• Severe allergic reaction during the first 4 doses of abatacept
• If any clinical events occur that preclude further dosing of abatacept, those patients will be deemed ineligible for randomization
DRUG: Placebo, DRUG: Abatacept
Graft Vs Host Disease
Study of S-606001 as an Add-on to Enzyme Replacement Therapy (ERT) in Participants With Late-onset Pompe Disease (LOPD)
Laurie Bailey - Laurie.Bailey@cchmc.org
ALL
18 years and over
PHASE2
NCT07123155
Key
• Deficiency of acid alpha-glucosidase (GAA) enzyme
• GAA genotype * Participant has a %FVC ≥30% and ≤80% in an upright position without mechanical ventilation at screening; or Participant has ≥10% %FVC drop from upright position to supine position and %FVC ≥20% in a supine position. * Participant performs the 6MWT at screening, as determined by the clinical evaluator, and meets all of the following criteria:
• Screening values of 6-minute walk distance (6MWD) are ≥75 meters
• Screening values of 6MWD are ≤90% of the predicted value for healthy adults * Participants must be ERT-experienced, defined as currently receiving ERT and having been receiving ERT for ≥24 months, with no regimen change in the last 6 months. Key
Inclusion Criteria:
* Participant must be ≥18 years of age and ≥40 kilograms (kg) of body weight at the time of signing the informed consent.
* Participant must have a diagnosis of LOPD based on documentation of 1 of the following:
• Deficiency of acid alpha-glucosidase (GAA) enzyme
• GAA genotype * Participant has a %FVC ≥30% and ≤80% in an upright position without mechanical ventilation at screening; or Participant has ≥10% %FVC drop from upright position to supine position and %FVC ≥20% in a supine position. * Participant performs the 6MWT at screening, as determined by the clinical evaluator, and meets all of the following criteria:
• Screening values of 6-minute walk distance (6MWD) are ≥75 meters
• Screening values of 6MWD are ≤90% of the predicted value for healthy adults * Participants must be ERT-experienced, defined as currently receiving ERT and having been receiving ERT for ≥24 months, with no regimen change in the last 6 months. Key
Exclusion Criteria:
* Has a medical condition or any other extenuating circumstance that may pose an undue safety risk to the participant or may compromise his/her ability to comply with or adversely impact protocol requirements.
* Has active infections at screening.
* Malignancy within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years.
* Current or chronic history of liver disease.
* Known biallelic loss of function mutations whether in glycogenin gene (GYG) or in glycogen phosphorylase muscle associated gene(PYGM) .
* Has received any investigational therapy or pharmacological treatment for Pompe disease, within 30 days or 5 half-lives of the therapy or treatment, whichever is longer, before day 1 or is anticipated to do so during the study.
* Has received gene therapy or small interfering ribonucleic acid (RNA) therapy for Pompe disease.
* Participant, if female, is pregnant or breastfeeding at screening.
* Participant, whether male or female, is planning to conceive a child during the study.
Note: Other protocol-specified inclusion and exclusion criteria may apply. DRUG: S-606001, DRUG: Placebo
Pompe Disease
Late-onset Pompe disease, Enzyme replacement therapy, LOPD, ERT, S-606001, Muscle glycogen synthase, Liver glycogen synthase, Rare disease, Autosomal disease, Acid alpha-glucosidase, GAA, Glycogen storage disorder, GSD
Safety and Efficacy of FETO in CDH Phase III (CDH FETO)
Foong-Yen Lim - foong.yen.lim@cchmc.org
FEMALE
18 years to 50 years old
PHASE3
NCT07187206
Inclusion Criteria:
* Pregnant women 18 years and older, who are able to consent
* Singleton pregnancy
* Gestational age at enrollment is prior to 296 weeks
* Intrathoracic liver herniation
* Isolated Left CDH with o/e LHR \< 30% at enrollment (180 to 295 weeks) or
* Isolated Right CDH with o/e LHR \< 45% at enrollment (180 to 295 weeks)
* Normal fetal karyotype with confirmation by culture results, CMA with non-pathological variants, WES or WGS. Results by fluorescence in situ hybridization (FISH) will be acceptable if the patient is \> 26 weeks
* Cervical length by transvaginal ultrasound \> 20 mm within 24 hours prior to FETO procedure
* Patient meets psychosocial criteria
* Informed consent understood
Exclusion Criteria
* Patient \< 18 years of age
* Multi-fetal pregnancy
* History of natural rubber latex allergy
* Preterm labor, cervix shortened (\< 20 mm at enrollment or within 24 hours prior to FETO balloon insertion) or uterine anomaly strongly predisposing to preterm labor, or placenta previa.
* Psychosocial ineligibility, precluding consent:
* Inability to reside within 30 minutes of Cincinnati Children's Hospital Medical Center and inability to comply with the travel for the follow-up requirements of the trial.
* The patient does not have a support person (e.g. spouse, partner, mother) available to stay with the patient for the duration of the pregnancy at Cincinnati Children's Hospital Medical Center.
* Bilateral CDH, isolated LCDH with o/e LHR ≥ 30%, isolated RCDH with o/e LHR \> 45%, as determined by ultrasound.
* No liver herniation into thoracic cavity
* Additional fetal anomaly and chromosomal abnormalities, associated anomalies recognized to alter survival prognosis (i.e., congenital heart disease) or presence of an underlying genetic syndrome (i.e., Fryns) by ultrasound, MRI, or echocardiogram at the fetal treatment center.
* Maternal contraindication to fetoscopic surgery or severe maternal medical condition in pregnancy
* History of incompetent cervix with or without cerclage
* Placental abnormalities (previa, abruption, accreta) known at time of enrollment
* Maternal-fetal Rh isoimmunization, Kell sensitization or neonatal alloimmune thrombocytopenia affecting the current pregnancy
* Maternal HIV, Hepatitis-B, Hepatitis-C positive because of the increased risk of transmission to the fetus during maternal-fetal surgery. If the patient's HIV status is unknown, the patient must be tested and found to have negative results before enrollment.
* Positive Hepatitis B surface antigen or presence of Hepatitis C in maternal blood uterine anomaly such as Mullerian duct abnormality, large or multiple fibroids that prohibit safe fetoscopic procedure
* There is no safe or technically feasible fetoscopic approach to balloon placement
* Participation in another intervention study that influences maternal and fetal morbidity and mortality, or participation in this trial in a previous pregnancy DEVICE: FETO, Fetal Endoluminal Tracheal Occlusion
Congenital Diaphragmatic Hernia, Pulmonary Hypoplasia, Pulmonary Hypertension
A Study of Uveitis in Children <18 Years of Age (UV1)
Shipra Rai - shipra.rai2@cchmc.org
ALL
Up to 17 years old
NCT07518134
Inclusion Criteria:
* Age:
* Incident cases (onset ≤ 6 months) \<17 years
* Established cases (onset \> 6 months) \<18 years
* Diagnosis of any type of uveitis (infectious or noninfectious) in any location except traumatic and post-operative uveitis.
* Active or inactive uveitis with any treatment status (current / prior / none \[but under surveillance\]).
Exclusion Criteria:
* Bilateral uveitis with differing etiologies
* Traumatic uveitis
* Post-operative uveitis
* Immediate family member (spouse, biological or legal guardian, child, sibling, parent) who is an investigative site personnel directly affiliated with this study or who is an employee of JAEB Center for Health Research.
* Ocular disease related to Retinoblastoma, Coat's disease, retinitis pigmentosa, inherited retinal degeneration, Juvenile xanthogranuloma (JXG), or leukemia/malignancy within the eye. Uveitis
pediatric, uveitis
Safety of RSV Preventive Monoclonal Antibody
Cathy Boyce - catherine.boyce@cchmc.org
ALL
6 weeks to 30 weeks old
PHASE4
NCT07158814
Inclusion Criteria:
* Infants ≥ 6 weeks to \<30 weeks of age at the time of enrollment
* Infants eligible for RSV monoclonal antibody and at least one routine childhood vaccine in outpatient clinic
* The parent/legal guardian must be willing and capable of providing permission for their infant to participate through the written informed consent process
* Parent/legal guardian must be able to read and comprehend English or Spanish
* The parent/legal guardian must be available for follow-up study contact by telephone from enrollment to completion of the study period
* The parent/legal guardian must agree to sign a medical record release for the infant so that study personnel may obtain medical information about the infant's health (if needed)
* The parent/legal guardian must be willing to delay their child's receipt of RSV monoclonal antibody up to two weeks from the scheduled date and to return for a second visit to receive the deferred RSV monoclonal antibody
Exclusion Criteria:
* Known contraindication or precaution to RSV monoclonal antibody or other routine vaccines being administered
* Received any vaccine within 14 days prior to enrollment and the first immunization day in this study
* Known previous receipt of RSV monoclonal antibody
* Received any experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 28 days prior to immunization in this study or expects to receive an experimental/investigational agent within the follow-up time period (8 days after the second immunization in this study)
* A moderate to severe acute illness and/or a reported temporal temperature greater than or equal to 100.4°F (38.0°C) within 48 hours prior to enrollment or a temporal temperature (measured by temporal artery thermometer) greater than or equal to 100.4°F (38.0°C) at the time of enrollment. (This may result in a temporary delay of immunization)
* Receipt of an antipyretic medication (acetaminophen or ibuprofen) within 48 hours prior to enrollment (This may result in a temporary delay of immunization)
* Planned receipt of a prophylactic antipyretic medication on the day of and/or days following immunization. This exclusion does not apply if the parent/legal guardian indicates they might administer antipyretics after immunization in response to fever or pain
* Has any condition that would, in the opinion of the site investigator, place the participant at an unacceptable risk of injury or render the participant unable to meet the requirements of the protocol
* Anyone who is a first-degree relative of any research study personnel
* The infant is born to a mother who received a maternal RSV immunization more than 14 days prior to delivery and is not eligible for RSV preventative monoclonal antibody
* Bleeding disorder or condition associated with prolonged bleeding that would present as a safety risk per opinion of the investigator
* History of severe adverse reaction associated with a vaccine and/or severe allergic reaction to any component of the vaccines or RSV monoclonal antibody
* Has an active neoplastic disease, or a history of any hematologic malignancy
* History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a component of a vaccine administered on the day of study enrollment
* Immunosuppression as a result of an underlying illness or treatment or use of anti-cancer chemotherapy or radiation therapy since birth
* For infants receiving DTaP vaccine (alone or combination vaccine): Encephalopathy (e.g., coma, decreased level of consciousness, prolonged seizures), not attributable to another identifiable cause, within 7 days of administration of previous dose of DTaP
* Intention to receive non-live or live vaccines during the 4 weeks after Visit 1; vaccines may be administered after enrollment if deemed a personal or public health priority by the health care provider caring for this patient or the study team
* Long term (at least 14 days of prednisone 2 mg/kg/day or equivalent other glucocorticoid) use of any parenteral steroids within the 6 months prior to enrollment (topical, nasal and inhaled steroids are allowed) DRUG: Respiratory Syncytial Virus (RSV) Preventive Monoclonal Antibody
Fever, Adverse Event Following Immunisation
Respiratory Syncytial Virus (RSV), Fever Following Immunization, RSV Monoclonal Antibody
Beeline: A Phase 3 Study in GRIN-related Neurodevelopmental Disorder
Katie Hall - Katie.Hall@cchmc.org
ALL
1 month to 18 years old
PHASE3
NCT07224581
Inclusion Criteria:
Part A, Participant:
* Diagnosed with GRIN-NDD with GRIN1, GRIN2A, GRIN2B, or GRIN2D gene variants known to result in GoF of the NMDA receptor
* Phase 3 Cohort 1 (Qualifying Seizures Cohort) ONLY: Experiencing at least 1 CMS per week and ≥4 CMS (generalized or focal) during screening
* With history of inadequate response to at least 2 standard antiseizure medications (ASMs)
* Phase 3 Cohort 2 (Without Qualifying Seizures Auxiliary Cohort) ONLY: With significant neurodevelopmental symptoms and a GRIN-CGI-S score ≥4
* On a stable dose of standard ASMs for at least 4 weeks prior to screening and should remain on stable doses throughout study participation
* On stable nonpharmacological treatments such as ketogenic diet and should remain stable throughout study participation
Part B:
\- Participant has completed Part A and is eligible to continue study participation according to the judgement of the investigator and sponsor.
Exclusion Criteria:
PART A, Participant:
* Has clinically relevant medical, neurologic, or psychiatric condition and/or behavioral disorder (including those related to GRIN-NDD) that would preclude or jeopardize participant's safe participation or study drug administration or the conduct of the study according to the judgement of the investigator or sponsor.
* Is receiving \>4 standard ASMs at screening
* Has a body weight of less than 5 kg at screening
Part B:
\- Participant has clinically relevant medical, neurologic, or psychiatric condition and/or behavioral disorder (including those related to GRIN-NDD) that would preclude or jeopardize participant's safe participation of study drug administration or the conduct of the study according to the judgement of the investigator or sponsor. DRUG: Radiprodil, DRUG: Placebo
GRIN-related Neurodevelopmental Disorder
Beeline, GRIN1, GRIN2A, GRIN2B, GRIN2D, GRIN-NDD
ARPKD Database Study (ARPKD)
Kelli Krallman - Kelli.Krallman@cchmc.org
ALL
Up to 18 years old
NCT01401998
Inclusion Criteria:
* Demonstration of hepato/renal fibrocystic disease by clinical information, imaging studies, biopsy, autopsy, or genetic testing.
Exclusion Criteria:
* ADPKD Urinary tract malformations Major congenital anomalies of other systems Hepato/Renal Fibrocystic Disease, Autosomal Recessive Polycystic Kidney Disease, Joubert Syndrome, Bardet Biedl Syndrome, Meckel-Gruber Syndrome, Congenital Hepatic Fibrosis, Caroli Syndrome, Oro-Facial-Digital Syndrome Type I, Nephronophthisis, Glomerulocystic Kidney Disease
cystic kidney disease, polycystic kidney disease, congenital hepatic fibrosis, genetic disease
COMPASSION S3 - Evaluation of the SAPIEN 3 Transcatheter Heart Valve in Patients With Pulmonary Valve Dysfunction
Amy Pajk - amy.pajk@cchmc.org
ALL
NA
NCT02744677
Inclusion Criteria:
• Weight ≥ 20 kg (44 lbs.)
• Dysfunctional RVOT conduit or previously implanted valve in the pulmonic position with a clinical indication for intervention and with a landing zone diameter ≥ 16.5 mm and ≤ 29 mm immediately prior to study device insertion as per the Instructions for Use
• Subject presents with at least moderate PR and/or mean RVOT gradient ≥ 35 mmHg.
• The subject/subject's legally authorized representative has been informed of the nature of the study, agrees to its provisions and has provided written informed consent.
Exclusion Criteria:
• Active infection requiring current antibiotic therapy (if temporary illness, subject may be a candidate 2 weeks after discontinuation of antibiotics)
• History of or active endocarditis (active treatment with antibiotics) within the past 180 days
• Leukopenia, anemia, thrombocytopenia or any known blood clotting disorder
• Inappropriate anatomy for femoral introduction and delivery of the study valve
• Need for concomitant atrial septal defect or ventricular septal defect closure or other concomitant interventional procedures other than pulmonary artery or branch pulmonary artery stenting or angioplasty
• Angiographic evidence of coronary artery compression that would result from transcatheter pulmonic valve implantation (TPVI)
• Interventional/surgical procedures within 30 days prior to the TPVI procedure.
• Any planned surgical, percutaneous coronary or peripheral procedure to be performed within the 30 day follow-up from the TPVI procedure.
• History of or current intravenous drug use
• Major or progressive non-cardiac disease resulting in a life expectancy of less than one year
• Known hypersensitivity to aspirin or heparin and cannot be treated with other antiplatelet and/or antithrombotic medications
• Known hypersensitivity to cobalt-chromium, nickel or contrast media that cannot be adequately premedicated
• Participating in another investigational drug or device study that has not reached its primary endpoint.
• Female who is lactating or pregnant
DEVICE: SAPIEN 3/SAPIEN 3 Ultra RESILIA THV, DEVICE: SAPIEN 3 THV, DEVICE: SAPIEN 3 Ultra RESILIA THV
Complex Congenital Heart Defect, Dysfunctional RVOT Conduit, Pulmonary Valve Insufficiency, Pulmonary Valve Degeneration
Tetralogy of Fallot, Aortic Valve Defect/Disease Resulting in Ross Procedure, Pulmonary Atresia, Pulmonary Stenosis, Truncus Arteriosus, Transposition of the Great Arteries, Transcatheter pulmonary valve implantation, Transcatheter pulmonary valve replacement, TPV, TPVR, TPVI
Tegavivint for the Treatment of Recurrent or Refractory Solid Tumors, Including Lymphomas and Desmoid Tumors
- cancer@cchmc.org
ALL
12 months to 30 years old
PHASE1
NCT04851119
Inclusion Criteria:
* PART A: Patients must be \>= 12 months and =\< 21 years of age at the time of study enrollment
* PART B: Patients must be \>= 12 months and =\< 30 years of age at the time of study enrollment
* Patients with recurrent or refractory solid tumors including non-Hodgkin lymphoma and desmoid tumors are eligible. Patients must have had histologic verification of malignancy at original diagnosis or relapse
* PART A: Patients with relapsed or refractory solid tumors, including patients with non-Hodgkin lymphoma and desmoid tumors
* PART B: Patients with recurrent or refractory Ewing sarcoma, desmoid tumors, osteosarcoma, liver tumors (HCC and hepatoblastoma), Wilms tumor, and tumors with Wnt pathway aberrations. For the Wnt pathway aberrations cohort we will include the most common CTNNB1 mutations (S37F, S45F, T41A, S45P, S33C, S37C, D32Y, S33F, T41I, G34R, G34V, D32N, S33P, G34E, D32G) as well as any loss of function mutations in the APC, Axin2FBXW7, TCF7L2, and RNF43 genes or any gain-of-function mutations in the GSK3B, LRP6, and LGR5 genes. For patients without prior sequencing, immunohistochemistry (IHC), is required. IHC showing strong nuclear beta-catenin staining will be accepted for the following tumor types: colorectal carcinoma, melanoma, endometrial cancer, ovarian cancer, neuroblastoma, non-Hodgkin lymphoma, pancreatic ductal adenocarcinoma, and solid pseudopapillary tumor of the pancreas
* PART A: Patients must have either measurable or evaluable disease. For desmoid tumors, the patient must have disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
* PART B: Patients must have measurable disease. For desmoid tumors, the patient must have measurable disease that the investigator deems unresectable or sufficiently morbid or potentially life-threatening that there is favorable risk/benefit to the patient to participate in the trial
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients \> 16 years of age and Lansky for patients =\< 16 years of age
* Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment. If after the required timeframe, the numerical eligibility criteria are met, e.g., blood count criteria, the patient is considered to have recovered adequately.
* Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive
* Solid tumor patients: \>= 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea)
* Non-Hodgkin lymphoma patients
* A waiting period prior to enrollment is not required for patients receiving standard maintenance chemotherapy (i.e., corticosteroid, vincristine, thioguanine \[6MP\], and/or methotrexate)
* \>= 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy
* NOTE: Cytoreduction with hydroxyurea must be discontinued \>= 24 hours prior to the start of protocol therapy
* Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil counts \[ANC\]): \>= 7 days after the last dose of agent
* Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1
* Corticosteroids: If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or 7 days for short acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur
* Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors)
* Stem cell Infusions (with or without total-body irradiation \[TBI\]):
* Allogeneic (non-autologous) bone marrow or stem cell transplant, or any stem cell infusion including donor lymphocyte infusion (DLI) or boost infusion: \>= 84 days after infusion and no evidence of graft versus host disease (GVHD)
* Autologous stem cell infusion including boost infusion: \>= 42 days.
* Cellular therapy: \>= 42 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.).
* External beam radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 150 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow (BM) radiation
* Radiopharmaceutical therapy (e.g., radiolabeled antibody, iobenguane I-131 \[131I MIBG\]): \>= 42 days after systemically administered radiopharmaceutical therapy
* Patients must not have received prior exposure to tegavivint
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Peripheral absolute neutrophil count (ANC) \>= 1000/uL (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Platelet count \>= 100,000/uL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS WITHOUT KNOWN BONE MARROW INVOLVEMENT: Hemoglobin \>= 8.0 g/dL at baseline (may receive red blood cell \[RBC\] transfusions) (within 7 days prior to enrollment)
* Patients with known bone marrow metastatic disease will be eligible for study provided they meet blood counts (may receive transfusions provided they are not known to be refractory to red cell or platelet transfusions). These patients will not be evaluable for hematologic toxicity. At least 5 of every cohort of 6 patients must be evaluable for hematologic toxicity for the dose-escalation part of the study. If dose-limiting hematologic toxicity is observed, all subsequent patients enrolled on Part A must be evaluable for hematologic toxicity
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2 or a creatinine based on age/gender as follows (within 7 days prior to enrollment):
* Age; maximum serum creatinine
* Age 1 to \< 2 years; 0.6 mg/dL (male); 0.6 mg/dL (female)
* Age 2 to \< 6 years; 0.8 mg/dL (male); 0.8 mg/dL (female)
* Age 6 to \< 10 years; 1 mg/dL (male); 1 mg/dL (female)
* Age 10 to \< 13 years; 1.2 mg/dL (male); 1.2 mg/dL (female)
* Age 13 to \< 16 years; 1.5 mg/dL (male); 1.4 mg/dL (female)
* Age \>= 16 years; 1.7 mg/dL (male); 1.4 mg/dL (female)
* PATIENTS WITH SOLID TUMORS: Bilirubin (sum of conjugated + unconjugated or total) =\< 1.5 x upper limit of normal (ULN) for age (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS: Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L. For the purpose of this study, the ULN for SGPT is 45 U/L (within 7 days prior to enrollment)
* PATIENTS WITH SOLID TUMORS: Albumin \>= 2 g/dL (within 7 days prior to enrollment)
Exclusion Criteria:
* Pregnant or breast-feeding women will not be entered on this study because there is yet no available information regarding human fetal or teratogenic toxicities. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use two effective methods of birth control, including a medically accepted barrier or contraceptive method (e.g., male or female condom) for the duration of the study. Abstinence is an acceptable method of birth control
* Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible. If used to modify immune adverse events related to prior therapy, \>= 14 days must have elapsed since last dose of corticosteroid
* Patients who are currently receiving another investigational drug are not eligible
* Patients who are currently receiving other anti-cancer agents are not eligible
* Patients who are receiving cyclosporine, tacrolimus or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial
* Patients who are currently receiving drugs that are strong inducers or inhibitors of CYP3A4 are not eligible. Strong inducers or inhibitors of CYP3A4 should be avoided from 14 days prior to the 1st dose of tegavivint to the end of the study
* Patients who have received bisphosphonates within 4 weeks prior to study enrollment will be excluded
* Patients who have received denosumab within 180 days prior to study enrollment will be excluded
* Patients with primary brain tumors are ineligible
* Patients with known central nervous system (CNS) metastasis, except for craniopharyngeal tumors, will be excluded
* Patients with a known metabolic bone disease (ex: hyperparathyroidism, Paget's disease, osteomalacia) are not eligible
* Patients with a disorder associated with abnormal bone metabolism will be excluded
* Patients with grade \>= 2 hypocalcemia that is not corrected with oral calcium supplementation will be excluded
* Patients with vitamin D \< 20 ng/mL will require supplementation, or will otherwise be excluded. Patients must agree to take vitamin D +/- calcium supplements (if necessary) according to institutional or published guidelines. Additional calcium supplementation is not required if adequate dietary intake can be ascertained
* Patients with pre-existing grade 3 osteoporosis are excluded
* Patients who have an uncontrolled infection are not eligible
* Patients who have received a prior solid organ transplantation are not eligible
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible PROCEDURE: Biospecimen Collection, PROCEDURE: Dual X-ray Absorptiometry, DRUG: Tegavivint, PROCEDURE: X-Ray Imaging
Colorectal Carcinoma, Endometrial Carcinoma, Melanoma, Neuroblastoma, Ovarian Carcinoma, Pancreatic Ductal Adenocarcinoma, Recurrent Desmoid Fibromatosis, Recurrent Ewing Sarcoma, Recurrent Hepatoblastoma, Recurrent Hepatocellular Carcinoma, Recurrent Malignant Solid Neoplasm, Recurrent Non-Hodgkin Lymphoma, Recurrent Osteosarcoma, Refractory Desmoid Fibromatosis, Refractory Ewing Sarcoma, Refractory Hepatoblastoma, Refractory Hepatocellular Carcinoma, Refractory Malignant Solid Neoplasm, Refractory Non-Hodgkin Lymphoma, Refractory Osteosarcoma, Solid Pseudopapillary Neoplasm of the Pancreas, Wilms Tumor
Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia
- cancer@cchmc.org
ALL
Up to 1 years old
PHASE2
NCT06317662
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrollment on AALL2321
* Infants (aged 365 days or less) on the date of diagnosis are eligible; infants must be \> 36 weeks gestational age (cumulative prenatal and postnatal age must be \> 36 weeks) at the time of enrollment
* Patients must have newly diagnosed B-acute lymphoblastic leukemia (B-ALL, 2017 World Health Organization \[WHO\] classification), also termed B-precursor ALL, or acute leukemia of ambiguous lineage (ALAL), which includes mixed phenotype acute leukemia. For patients with ALAL, the immunophenotype of the leukemia must comprise at least 50% B lineage
* Diagnostic immunophenotype: Leukemia cells must express CD19
Exclusion Criteria:
* Patients with Down Syndrome
* Patients with secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy
* Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of infant ALL or for any cancer diagnosis prior to the initiation of protocol therapy, with the exception of:
* Steroid pretreatment:
* PredniSONE, prednisoLONE, or methylPREDNISolone for ≤ 72 hours (3 days) in the 7 days prior to enrollment. The dose of predniSONE, prednisoLONE or methylPREDNISolone does not affect eligibility
* Inhaled and topical steroids are not considered pretreatment
* Note: Pretreatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone used during or within 6 hours prior to or after sedation to prevent or treat airway edema. However, prior exposure to ANY steroids that occurred \> 28 days before enrollment does not affect eligibility
* Intrathecal cytarabine or methotrexate:
* An intrathecal dose of cytarabine or methotrexate in the 7 days prior to enrollment does not affect eligibility
* Note: The preference is to defer the diagnostic lumbar puncture with intrathecal chemotherapy to day 1 of induction to allow for cytoreduction of circulating blasts and decrease the potential for central nervous system (CNS) contamination due to a traumatic tap. If done prior to day 1 of induction, these results will be used to determine CNS status
* Hydroxyurea:
* Pretreatment with ≤ 72 hours (3 days) of hydroxyurea in the 7 days prior to enrollment does not affect eligibility
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA) and National Cancer Institute (NCI) requirements for human studies must be met DRUG: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Aspiration, DRUG: Calaspargase Pegol, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Daunorubicin, DRUG: Dexamethasone, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, PROCEDURE: FDG-Positron Emission Tomography, DRUG: Leucovorin, DRUG: Levoleucovorin, PROCEDURE: Lumbar Puncture, PROCEDURE: Magnetic Resonance Imaging, DRUG: Mercaptopurine, DRUG: Methotrexate, DRUG: Methylprednisolone, PROCEDURE: Multigated Acquisition Scan, DRUG: Prednisolone, DRUG: Prednisone, DRUG: Therapeutic Hydrocortisone, DRUG: Thioguanine, DRUG: Venetoclax, DRUG: Vincristine
Acute Leukemia of Ambiguous Lineage, B Acute Lymphoblastic Leukemia
Adolescent Outcomes of Post-operative Opioid EXposure (APEX)
Isabelle Allen - Isabelle.Allen@cchmc.org
ALL
12 years to 17 years old
NCT06350409
Adolescent Inclusion Criteria
• Adolescents between the ages of 12 to 17 years old, inclusive, who are scheduled to undergo a scheduled surgical procedure with a greater than 90% likelihood of requiring opioid analgesia for at least 48 hours post-operatively (as an inpatient) or discharged home with at least a 48-hour supply of prescription opioids. • Opioid prescribing practices vary by institution; therefore, eligible surgical procedures will be determined on a site-by-site basis.
• Adolescents willing and able to provide informed assent and have a parent/caregiver willing to provide informed consent. Parent/Caregiver Inclusion Criteria
• Parent or legal guardian of an eligible adolescent.
• Parent or legal guardian willing and able to provide written informed consent. Adolescent Exclusion Criteria Adolescents meeting any of the following criteria will be excluded from study participation:
• Adolescents who have been prescribed opioids in the past 2 years for pain due to a chronic medical condition.
• Adolescents who have a current chronic medical condition that requires ongoing opioid pain management and treatment such as sickle cell disease, arthritis, or cancer.
• Adolescents who do not have a caregiver who is willing to co-participate in the study.
• Adolescents who cannot speak or read English at a 4th-grade level as determined by medical or research staff.
• Adolescents who are currently in the custody of the Department of Youth Services, jail/prison, or other overnight facility as required by court of law or have pending legal action that could prevent participation in study activities.
• Adolescents who are currently in the custody of the Department of Children and Families or living with a foster family.
• Adolescents who are currently pregnant or parenting.
• Adolescents that self or parent report of ever having been diagnosed with opioid use disorder, or prescribed buprenorphine, methadone, or naltrexone to treat opioid use disorder.
• Adolescents who are currently enrolled in an intervention study that aims to impact opioid prescription or pain management pre-, peri-, or post-operatively. Parent/Caregiver Exclusion Criteria Parents/Caregivers meeting any of the following criteria will be excluded from study participation:
• Parents/Caregivers who cannot speak or read English or Spanish at a 4th grade level as determined by medical or research staff.
• Parents/Caregivers that are currently incarcerated.
• Parents/Caregivers that are in physical or mental distress that precludes study participation as determined by clinical or study staff.
• Adolescents between the ages of 12 to 17 years old, inclusive, who are scheduled to undergo a scheduled surgical procedure with a greater than 90% likelihood of requiring opioid analgesia for at least 48 hours post-operatively (as an inpatient) or discharged home with at least a 48-hour supply of prescription opioids. • Opioid prescribing practices vary by institution; therefore, eligible surgical procedures will be determined on a site-by-site basis.
• Adolescents willing and able to provide informed assent and have a parent/caregiver willing to provide informed consent. Parent/Caregiver Inclusion Criteria
• Parent or legal guardian of an eligible adolescent.
• Parent or legal guardian willing and able to provide written informed consent. Adolescent Exclusion Criteria Adolescents meeting any of the following criteria will be excluded from study participation:
• Adolescents who have been prescribed opioids in the past 2 years for pain due to a chronic medical condition.
• Adolescents who have a current chronic medical condition that requires ongoing opioid pain management and treatment such as sickle cell disease, arthritis, or cancer.
• Adolescents who do not have a caregiver who is willing to co-participate in the study.
• Adolescents who cannot speak or read English at a 4th-grade level as determined by medical or research staff.
• Adolescents who are currently in the custody of the Department of Youth Services, jail/prison, or other overnight facility as required by court of law or have pending legal action that could prevent participation in study activities.
• Adolescents who are currently in the custody of the Department of Children and Families or living with a foster family.
• Adolescents who are currently pregnant or parenting.
• Adolescents that self or parent report of ever having been diagnosed with opioid use disorder, or prescribed buprenorphine, methadone, or naltrexone to treat opioid use disorder.
• Adolescents who are currently enrolled in an intervention study that aims to impact opioid prescription or pain management pre-, peri-, or post-operatively. Parent/Caregiver Exclusion Criteria Parents/Caregivers meeting any of the following criteria will be excluded from study participation:
• Parents/Caregivers who cannot speak or read English or Spanish at a 4th grade level as determined by medical or research staff.
• Parents/Caregivers that are currently incarcerated.
• Parents/Caregivers that are in physical or mental distress that precludes study participation as determined by clinical or study staff.
Opioid Use Disorder, Pain, Chronic
Adolescent Opioid Use, Post operative pain
Belumosudil to Block Chronic Lung Allograft Dysfunction (CLAD) in High Risk Lung Transplant Recipients (CLAD)
Maryam Mysorewala - maryam.mysorewala@cchmc.org
ALL
12 years and over
PHASE2
NCT06476132
Inclusion Criteria:
• Participant and/or parent or guardian must be able to understand the purpose of the study, willing to participate, sign the informed consent, and if applicable assent.
• Single or bilateral lung transplant recipient age ≥ 12 years
• A qualifying biopsy obtained 60 to 760 days after lung transplant with evidence of allograft injury histology; a qualifying biopsy must have one or more of the following features alone or in combination: Acute Rejection (AR), Lymphocytic Bronchiolitis (LB), Organizing Pneumonia (OP), or Acute Lung Injury (ALI). The presence of any grade AR (A1 or greater) or LB (B1 or greater) qualifies for inclusion
• Females of reproductive potential and males with female partners of reproductive potential must agree to use effective contraception during treatment with belumosudil or placebo and for at least 3 months after the last dose. Participants must agree to refrain from donating or cryopreserving sperm, eggs (ova or ovocytes) for the purpose of reproduction during treatment with belumosudil or placebo and for at least 3 months after the last dose.
• Meeting hematologic laboratory criteria: absolute neutrophil count (ANC) \>= 0.5 x 10(9)/L and platelet count \>= 50 x 10(9)/L within 30 days of enrollment
• Meeting all blood chemistry laboratory criteria: aspartate aminotransferase (AST) or alanine transaminase (ALT) \< 2x upper limit of normal (ULN), bilirubin \< 1.5x ULN unless due to Gilbert's syndrome, estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73m2 within 30 days of enrollment
• Cytomegalovirus (CMV) polymerase chain reaction (PCR) negative or, if detected, \<200 IU/ml in the absence of any signs of active infection, within 30 days of enrollment
• In the absence of contraindications, must have received adult vaccinations or documented immunity as outlined in current National Institute of Allergy and Infectious Diseases (NIAID) Division of Allergy, Immunology, and Transplantation (DAIT) Guidance for Patients in Transplant Trials
• Intent to receive calcineurin inhibitor (CNI)-based maintenance Immunosuppression (IS) regimen
Exclusion Criteria:
• Multi-organ transplants involving more than one organ type (e.g., heart-lung)
• Prior organ transplant or prior bone marrow transplant/hematopoietic stem cell transplantation
• Greater than 160 days after a qualifying biopsy
• Active AMR unless resolved and no treatments with prohibited medications for \> 90 days prior to enrollment
• Diagnosed with probable or definite CLAD according to International Society for Heart and Lung Transplantation (ISHLT) guidelines prior to enrollment.
• Posttransplant treatment with anti-thymocyte globulin within 30 days or alemtuzumab or any other prohibited medication within 90 days prior to enrollment.
• Epstein-Barr virus (EBV) seronegative recipient who received EBV positive donor lung(s).
• Treatment with any other investigational pharmacologic agent within 30 days prior to enrollment.
• Significant active uncontrolled infection which, in the opinion of the investigator, would place the participant at increased risk.
• Current use of sirolimus or everolimus.
• Recipient human immunodeficiency virus (HIV) positive.
• Recipient Hepatitis B surface antigen positive or Hepatitis B core antibody positive.
• Received lung(s) from a donor with known Hepatitis B virus (HBV) including Hepatitis B core antibody positive donors.
• Incompletely treated Hepatitis C (absence of ongoing treatment and post-transplant negative HCV PCR)
• History of clinically significant surgical factors (such as phrenic nerve damage, transplant lung resection, chest wall surgery), or mechanical factors (such as posttransplant airways disease including bronchial dehiscence, stenosis, dilation, or stent placement, pleural disease) that impedes lung function.
• Past or current medical problems, psychosocial concerns, or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose undue risk from participation in the study, may interfere with the participant's ability to comply with study requirements, or that may impact the quality or interpretation of the data obtained from the study.
• Pregnant or breastfeeding
DRUG: Belumosudil, DRUG: Placebo for Belumosudil
Lung Transplant
Lung Transplant, Belumosudil, CLAD, Acute Rejection, Lymphocytic Bronchiolitis, Organizing Pneumonia, Acute Lung Injury
Identification of Biomarkers for Patients with Vascular Anomalies
- hvmcresearch@cchmc.org
ALL
Not specified
NCT03001180
Inclusion Criteria:
* Any patient having labs drawn as standard of care will have blood drawn for the study if consented/ assented.
* All patients who are undergoing a surgical procedure or sclerotherapy are currently consented for participation in the tissue bank.
Exclusion Criteria:
* N/A Vascular Anomaly, Generalized Lymphatic Anomaly, Kaposiform Hemangioendothelioma, Kaposiform Lymphangiomatosis, Gorham-Stout Disease, Klippel Trenaunay Syndrome, Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi
Generalized Lymphatic Anomaly, Vascular Anomaly, Kaposiform Hemangioendothelioma, Kaposiform Lymphangiomatosis, Vascular Endothelial Growth Factor, Biomarkers, GLA, KLA, KHE, GSD
PEP-CMV Vaccine Targeting CMV Antigen to Treat Newly Diagnosed Pediatric HGG and DIPG and Recurrent Medulloblastoma
- cancer@cchmc.org
ALL
3 years to 39 years old
PHASE2
NCT05096481
Inclusion Criteria for patients with recurrent /progressive medulloblastoma (stratum I)
• Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
• Diagnosis: Patients must have a diagnosis of medulloblastoma that is recurrent, progressive or refractory. All patients must have histological verification of a medulloblastoma, at original diagnosis or relapse. • Patients must have measurable disease defined as a lesion that can be measured in two perpendicular diameters on MRI.
• Metastatic Disease: Patients with M+ disease are eligible.
• Performance Status: Karnofsky ≥ 50% for patients \>16 years of age or Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy:
• Radiotherapy: prior radiotherapy requirements Patients must have received prior disease-directed therapy including radiotherapy for their initial diagnosis of medulloblastoma unless patients are less than 4 years of age at the time of enrollment. For those less than 4 years of age at the time of enrollment, prior disease directed therapy does not have to include prior radiotherapy. Patients must have had their last fraction of: * Craniospinal irradiation, total body irradiation or radiation to ≥ 50% of pelvis \> 3 months prior to enrollment. * Focal irradiation \> 4 weeks prior to enrollment
• Myelosuppressive anticancer therapy: Patients must have received their last dose of myelosuppressive anticancer therapy at least 21 days prior to enrollment
• Immunotherapy: Patients must have received their last dose of any immunotherapy agents at least 30 days prior to enrollment
• Non-myelosuppressive anticancer agents: Patients must have received their last dose of non-myelosuppressive anticancer agents at least 7 days prior to study enrollment.
• Antibodies: Patients must have received their last dose of any antibodies at least 21 days prior to enrollment.
• Hematopoietic growth factors: Patients must have received their last dose of hematopoietic growth factors at least 14 days prior to enrollment for a long-acting growth factor (e.g. pegfilgrastim) or 7 days prior to enrollment for short-acting growth factor.
• Autologous stem cell infusion: At least 90 days must have elapsed after an autologous stem cell infusion
• Organ Function Requirements:
• Adequate bone marrow function defined as: * ANC (Absolute neutrophil count) ≥ 1000/µl. * Platelets ≥ 100,000/µl. (may be supported) * Hemoglobin \> 8 g/dL. (may be supported)
• Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or A serum creatinine based on age/gender as follows: Age: Maximum Serum Creatinine (mg/dL) * 2 to \< 6 years: 0.8 (Male) 0.8 (Female) * 6 to \< 10 years: 1 (Male) 1 (Female) * 10 to \< 13 years: 1.2 (Male) 1.2 (Female) * 13 to \< 16 years: 1.5 (Male) 1.4 (Female) * ≥ 16 years: 1.7 (Male) 1.4 (Female)
• Adequate Liver Function Defined as * Total bilirubin ≤1.5 times institutional ULN * AST(SGOT) ≤3 × institutional upper limit of normal * ALT(SGPT) ≤3 × institutional upper limit of normal
• Adequate Neurological Function Defined as * Patients with neurological deficits should have deficits that are stable for a minimum of 2 weeks prior to enrollment. * Patients with current seizure disorders may be enrolled if seizures are well- controlled on antiepileptic therapies.
• Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for three months after drug cessation.
• Signed informed consent according to institutional guidelines must be obtained prior to enrollment. Inclusion Criteria for Patients with Newly-Diagnosed High-Grade Gliomas (HGG) (stratum II, CLOSED on 19Aug2026) and Newly-Diagnosed (DIPG) (stratum III)
• Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
• Diagnosis
• Stratum II \[CLOSED on 19Aug2026\]: patients must have histologically confirmed, newly-diagnosed HGG (such as anaplastic astrocytoma, glioblastoma, H3K27-altered DMG). * Patients with a newly-diagnosed HGG must enroll within 6 weeks of their final dose of standard radiation therapy with or without chemotherapy. * Patients with primary spinal cord tumors are eligible
• Stratum III: Patients with a newly-diagnosed DIPG: * Patients with a radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation. * Patients with brainstem lesions that do not meet these radiographic criteria will be eligible if there is histologic confirmation of an infiltrating astrocytoma WHO grades II-IV.
• Metastatic Disease: Patients with M+ disease are eligible.
• Performance Status: Karnofsky ≥ 50 for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy requirements: Patients must have received no prior therapy other than surgery, radiation, chemotherapy during radiotherapy and/or steroids (dexamethasone with goal to wean dexamethasone throughout protocol therapy). Patients with a newly diagnosed high-grade glioma or DIPG must enroll within 6 weeks of their final dose of standard of care radiation therapy with or without chemotherapy.
• Patients with HGG or DIPG are permitted, but not required, to have received chemotherapy during radiation. Bevacizumab is permitted prior to enrollment in patients with DIPG or HGG. Patients must have received their last dose of bevacizumab at least 14 days prior to enrollment.
• For HGG patients, Patients must have received radiotherapy at a standard dose of 54-59.4 Gy in 1.8 Gy fractions for approximately 6 weeks with an acceptable variance of 10%. Radiation therapy must have begun no later than 42 days after the date definitive surgery.
• For patients with DIPG, Patients must have received radiotherapy at a standard dose of radiotherapy of 54 Gy in 1.8 Gy daily fractions for approximately 6 weeks with an acceptable variance rate of 10%. Radiation therapy must have begun no later than 42 days after the date of radiographic diagnosis or biopsy
• For patients with spinal cord HGG: Patients must have received radiotherapy at a standard dose of 45-54 Gy in 1.8 Gy fractions for approximately 6-7 weeks with an acceptable variance of 10%
• For patients with metastatic disease: Patients may have received standard dose CSI
• Organ Function Requirements:
• Adequate bone marrow function defined as • ANC (Absolute neutrophil count) ≥ 1000/µl. • Platelets ≥ 100,000/µl. (may be supported) • Hemoglobin \> 8 g/dL. (may be supported)
• Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or A serum creatinine based on age/gender as follows: Age: Maximum Serum Creatinine (mg/dL) • 2 to \< 6 years: 0.8 (Male) 0.8 (Female) • 6 to \< 10 years: 1 (Male) 1 (Female) • 10 to \< 13 years: 1.2 (Male) 1.2 (Female) • 13 to \< 16 years: 1.5 (Male) 1.4 (Female) • ≥ 16 years: 1.7 (Male) 1.4 (Female)
• Adequate Liver Function Defined as: • Total bilirubin ≤1.5 times institutional ULN * AST(SGOT) ≤3 × institutional upper limit of normal * ALT(SGPT) ≤3 × institutional upper limit of normal
• Adequate Neurological Function Defined as: Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. d. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study. e. Signed informed consent according to institutional guidelines must be obtained prior to registration and for 3 months after drug cessation. Exclusion Criteria for all strata:
• Pregnancy or Breast-Feeding:
• Pregnant or breast-feeding women will not be entered on this study due to known or unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-monarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 3 months after drug cessation.
• Study Specific:
• Active infection requiring treatment
• Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history
• Known immunosuppressive disease
• Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or moderate to severe pulmonary problems generally defined by need for medical intervention (e.g., oxygen, medications) and/or limiting activities of daily living (generally CTCAE Grade 2 or higher) or shortness of breath with limited exertion are not eligible. Pulmonary conditions include (but are not limited to) COPD, asthma, and hemi-pneumectomy
• Patients receiving concomitant immunosuppressive agents for medical conditions; inhaled corticosteroids for asthma are allowed.
• Patients receiving concomitant tumor-directed therapy
• Patients receiving any other investigational drug therapy.
• Patients on dexamethasone \> 0.1 mg/Kg/day up to maximum dose of 4 mg/day or equivalent.
• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
• Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
• Patients at high risk for imminent neurologic decline due to extensive bulk disease, midline shift, or herniation on MRI. These patients should be discussed with the study chairs.
• Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
• Diagnosis: Patients must have a diagnosis of medulloblastoma that is recurrent, progressive or refractory. All patients must have histological verification of a medulloblastoma, at original diagnosis or relapse. • Patients must have measurable disease defined as a lesion that can be measured in two perpendicular diameters on MRI.
• Metastatic Disease: Patients with M+ disease are eligible.
• Performance Status: Karnofsky ≥ 50% for patients \>16 years of age or Lansky ≥ 50 for patients ≤ 16 years of age. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy:
• Radiotherapy: prior radiotherapy requirements Patients must have received prior disease-directed therapy including radiotherapy for their initial diagnosis of medulloblastoma unless patients are less than 4 years of age at the time of enrollment. For those less than 4 years of age at the time of enrollment, prior disease directed therapy does not have to include prior radiotherapy. Patients must have had their last fraction of: * Craniospinal irradiation, total body irradiation or radiation to ≥ 50% of pelvis \> 3 months prior to enrollment. * Focal irradiation \> 4 weeks prior to enrollment
• Myelosuppressive anticancer therapy: Patients must have received their last dose of myelosuppressive anticancer therapy at least 21 days prior to enrollment
• Immunotherapy: Patients must have received their last dose of any immunotherapy agents at least 30 days prior to enrollment
• Non-myelosuppressive anticancer agents: Patients must have received their last dose of non-myelosuppressive anticancer agents at least 7 days prior to study enrollment.
• Antibodies: Patients must have received their last dose of any antibodies at least 21 days prior to enrollment.
• Hematopoietic growth factors: Patients must have received their last dose of hematopoietic growth factors at least 14 days prior to enrollment for a long-acting growth factor (e.g. pegfilgrastim) or 7 days prior to enrollment for short-acting growth factor.
• Autologous stem cell infusion: At least 90 days must have elapsed after an autologous stem cell infusion
• Organ Function Requirements:
• Adequate bone marrow function defined as: * ANC (Absolute neutrophil count) ≥ 1000/µl. * Platelets ≥ 100,000/µl. (may be supported) * Hemoglobin \> 8 g/dL. (may be supported)
• Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or A serum creatinine based on age/gender as follows: Age: Maximum Serum Creatinine (mg/dL) * 2 to \< 6 years: 0.8 (Male) 0.8 (Female) * 6 to \< 10 years: 1 (Male) 1 (Female) * 10 to \< 13 years: 1.2 (Male) 1.2 (Female) * 13 to \< 16 years: 1.5 (Male) 1.4 (Female) * ≥ 16 years: 1.7 (Male) 1.4 (Female)
• Adequate Liver Function Defined as * Total bilirubin ≤1.5 times institutional ULN * AST(SGOT) ≤3 × institutional upper limit of normal * ALT(SGPT) ≤3 × institutional upper limit of normal
• Adequate Neurological Function Defined as * Patients with neurological deficits should have deficits that are stable for a minimum of 2 weeks prior to enrollment. * Patients with current seizure disorders may be enrolled if seizures are well- controlled on antiepileptic therapies.
• Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for three months after drug cessation.
• Signed informed consent according to institutional guidelines must be obtained prior to enrollment. Inclusion Criteria for Patients with Newly-Diagnosed High-Grade Gliomas (HGG) (stratum II, CLOSED on 19Aug2026) and Newly-Diagnosed (DIPG) (stratum III)
• Age: Patients must be ≥3 and ≤39 years of age at the time of study enrollment
• Diagnosis
• Stratum II \[CLOSED on 19Aug2026\]: patients must have histologically confirmed, newly-diagnosed HGG (such as anaplastic astrocytoma, glioblastoma, H3K27-altered DMG). * Patients with a newly-diagnosed HGG must enroll within 6 weeks of their final dose of standard radiation therapy with or without chemotherapy. * Patients with primary spinal cord tumors are eligible
• Stratum III: Patients with a newly-diagnosed DIPG: * Patients with a radiographically typical DIPG, defined as a tumor with a pontine epicenter and diffuse involvement of more than 2/3 of the pons, are eligible without histologic confirmation. * Patients with brainstem lesions that do not meet these radiographic criteria will be eligible if there is histologic confirmation of an infiltrating astrocytoma WHO grades II-IV.
• Metastatic Disease: Patients with M+ disease are eligible.
• Performance Status: Karnofsky ≥ 50 for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy requirements: Patients must have received no prior therapy other than surgery, radiation, chemotherapy during radiotherapy and/or steroids (dexamethasone with goal to wean dexamethasone throughout protocol therapy). Patients with a newly diagnosed high-grade glioma or DIPG must enroll within 6 weeks of their final dose of standard of care radiation therapy with or without chemotherapy.
• Patients with HGG or DIPG are permitted, but not required, to have received chemotherapy during radiation. Bevacizumab is permitted prior to enrollment in patients with DIPG or HGG. Patients must have received their last dose of bevacizumab at least 14 days prior to enrollment.
• For HGG patients, Patients must have received radiotherapy at a standard dose of 54-59.4 Gy in 1.8 Gy fractions for approximately 6 weeks with an acceptable variance of 10%. Radiation therapy must have begun no later than 42 days after the date definitive surgery.
• For patients with DIPG, Patients must have received radiotherapy at a standard dose of radiotherapy of 54 Gy in 1.8 Gy daily fractions for approximately 6 weeks with an acceptable variance rate of 10%. Radiation therapy must have begun no later than 42 days after the date of radiographic diagnosis or biopsy
• For patients with spinal cord HGG: Patients must have received radiotherapy at a standard dose of 45-54 Gy in 1.8 Gy fractions for approximately 6-7 weeks with an acceptable variance of 10%
• For patients with metastatic disease: Patients may have received standard dose CSI
• Organ Function Requirements:
• Adequate bone marrow function defined as • ANC (Absolute neutrophil count) ≥ 1000/µl. • Platelets ≥ 100,000/µl. (may be supported) • Hemoglobin \> 8 g/dL. (may be supported)
• Adequate Renal Function defined as: Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 or A serum creatinine based on age/gender as follows: Age: Maximum Serum Creatinine (mg/dL) • 2 to \< 6 years: 0.8 (Male) 0.8 (Female) • 6 to \< 10 years: 1 (Male) 1 (Female) • 10 to \< 13 years: 1.2 (Male) 1.2 (Female) • 13 to \< 16 years: 1.5 (Male) 1.4 (Female) • ≥ 16 years: 1.7 (Male) 1.4 (Female)
• Adequate Liver Function Defined as: • Total bilirubin ≤1.5 times institutional ULN * AST(SGOT) ≤3 × institutional upper limit of normal * ALT(SGPT) ≤3 × institutional upper limit of normal
• Adequate Neurological Function Defined as: Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment. d. Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study. e. Signed informed consent according to institutional guidelines must be obtained prior to registration and for 3 months after drug cessation. Exclusion Criteria for all strata:
• Pregnancy or Breast-Feeding:
• Pregnant or breast-feeding women will not be entered on this study due to known or unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-monarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Pregnancy Prevention Patients of childbearing or child fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study and for 3 months after drug cessation.
• Study Specific:
• Active infection requiring treatment
• Patients with malignancy related to HIV or solid organ transplant: known history of HIV, HBV surface antigen positivity or positive HCV antibody are not eligible. Viral testing is not required unless clinically indicated in patients without a known history
• Known immunosuppressive disease
• Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or moderate to severe pulmonary problems generally defined by need for medical intervention (e.g., oxygen, medications) and/or limiting activities of daily living (generally CTCAE Grade 2 or higher) or shortness of breath with limited exertion are not eligible. Pulmonary conditions include (but are not limited to) COPD, asthma, and hemi-pneumectomy
• Patients receiving concomitant immunosuppressive agents for medical conditions; inhaled corticosteroids for asthma are allowed.
• Patients receiving concomitant tumor-directed therapy
• Patients receiving any other investigational drug therapy.
• Patients on dexamethasone \> 0.1 mg/Kg/day up to maximum dose of 4 mg/day or equivalent.
• Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
• Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy
• Patients at high risk for imminent neurologic decline due to extensive bulk disease, midline shift, or herniation on MRI. These patients should be discussed with the study chairs.
BIOLOGICAL: PEP-CMV, DRUG: Temozolomide, BIOLOGICAL: Tetanus Diphtheria Vaccine
High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Recurrent Medulloblastoma
High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Recurrent Medulloblastoma, Immunotherapy
Study of Revumenib, Azacitidine, and Venetoclax in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia
- cancer@cchmc.org
ALL
1 year to 30 years old
PHASE1
NCT06177067
Inclusion Criteria:
Participants must have a diagnosis of AML or ALAL and meet the criteria below:
* Refractory leukemia, defined as persistent leukemia after at least two courses of induction chemotherapy (one course for secondary AML), or relapsed leukemia, defined as the re-appearance of leukemia after the achievement of remission. Patients must have ≥5% blasts in the bone marrow as assessed by morphology or ≥1% blasts flow cytometry.
However, if an adequate bone marrow sample cannot be obtained (e.g., in a patient with acute megakaryoblastic leukemia with marrow fibrosis), patients may be enrolled if there is unequivocal evidence of leukemia with ≥5% blasts by morphology or ≥1% blasts flow cytometry in the blood.
* Presence of KMT2A rearrangement (KMT2Ar), NUP98 rearrangement (NUP98r), NPM1 mutation or fusion, PICALM::MLLT10, DEK::NUP214, UBTF-TD, KAT6A rearrangement (KAT6Ar), or SET::NUP214
* Adequate organ function, defined as total bilirubin \< 1.5 × institutional upper limit of normal for age or normal conjugated bilirubin (for patients with known Gilbert's syndrome, total bilirubin \<3 × the ULN) unless attributed to leukemia, calculated creatinine clearance ≥60 mL/min/1.73 m\^2, and left ventricular ejection fraction ≥ 40%
* QTcF \< 480 msec (average of triplicate)
* Age ≥ 1 year and ≤ 30 years. The upper age limit may be defined by each institution, but may not exceed 30 years.
* Lansky ≥ 60 for patients who are \< 16 years old and Karnofsky ≥ 60% for patients who are \> 16 years old.
* At least 14 days or 5 half-lives (whichever is longer) must have elapsed since the completion of myelosuppressive therapy, with the exception of low-dose therapy used for cytoreduction according to institutional standards, such as hydroxyurea or low-dose cytarabine (up to 200 mg/m\^2/day). In addition, all toxicities must have resolved to grade 1 or less.
* Patients must have a leukocyte count \<25,000 cells/uL. Low-dose therapy, such as hydroxyurea or cytarabine as described above, to achieve this limit is acceptable.
* For patients who have received prior HCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HCT, and patients should be off calcineurin inhibitors for at least 28 days prior to the start of protocol therapy. Physiologic prednisone for the treatment of adrenal insufficiency is acceptable..
* Patients must be taking posaconazole or voriconazole, which must be started at least 24 hours prior to the start of therapy.
* Patients of reproductive potential must agree to use effective contraception for the duration of study participation.
Patients who meet the criteria listed above are eligible for enrollment and treatment on the trial. However, patients in first relapse who are suitable for and willing to receive intensive remission induction therapy should be offered such therapy if deemed appropriate by the treating physician.
Exclusion Criteria:
* Patients who are pregnant or breastfeeding are not eligible.
* Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndromes are not eligible.
* Patients with uncontrolled infection are not eligible. Patients with infections that are controlled on concurrent anti-microbial agents are eligible. DRUG: Revumenib, DRUG: Venetoclax, DRUG: Azacitidine, DRUG: intrathecal (IT) chemotherapy, DRUG: Cytarabine, DRUG: Methotrexate
Refractory Acute Myeloid Leukemia, Relapsed Acute Myeloid Leukemia, Acute Leukemia of Ambiguous Lineage
Minima Stent System Post- Approval Study (PAS)
Amy Pajk - amy.pajk@cchmc.org
ALL
NCT06828770
Inclusion Criteria:
* The subject's legally authorized representative has been informed of the nature of the device treatment, agrees to its provisions, and has provided written informed consent
* Indicated for treatment with the Minima Stent System per the IFU.
Exclusion Criteria:
* Active bloodstream infection requiring antibiotic therapy within 3 days prior to stent implantation
* History of or active endocarditis (active treatment with antibiotics) within 180 days prior to stent implantation
* Aortic or pulmonary artery aneurysm in the location targeted for treatment
* Body weight \< 1.5 kg
* Anatomic location of lesion judged by the investigator to not lend to the safe placement of a stent
* Target vessels larger or smaller than the Minima System balloon size ranges
* Known genetic syndrome known to be associated with vasculopathies such as but not limited to Williams syndrome, Loeys-Dietz syndrome, etc
* Clinical scenario requiring that more than one vessel needs stent implantation at the time of the trial procedure.
* Currently participating in an investigational drug study or another device study
* Major or progressive non-cardiac disease resulting in a life expectancy of less than six months
* Known hypersensitivity to aspirin or heparin and cannot be treated with other antiplatelet and/or antithrombotic medications
* Known hypersensitivity to cobalt-chromium or contrast media that cannot be adequately premedicated DEVICE: Minima Stent System
Pulmonary Artery Stenosis, Aortic Coarctation
Vascular Stenosis, Minima, Minima Stent, Minima Stent System, Renata Medical, Renata, infant stent
The Pediatric Anesthesia Quality Improvement Project (WUS)
Geisler Kristie - kristie.geisler@cchmc.org
ALL
Up to 21 years old
NCT00674388
Inclusion Criteria:
* All children undergoing anesthesia at participating hospitals
Exclusion Criteria:
* Patients over 21 years of age Surgery, Anesthesia, Children
Children, Anesthesia, Surgery, Complication
SMART@Home Feasibility Trial
Jessica King - jessica.king1@cchmc.org
ALL
12 years to 18 years old
NA
NCT06159127
Inclusion Criteria:
* Patients diagnosed with a chronic medical condition requiring regular treatment, i.e., asthma
* Ages 12-18
* English fluency for patient and caregiver
Exclusion Criteria:
* Diagnosis of pervasive developmental disorder in patient or caregiver as determined by medical chart review
* Diagnosis of serious mental illness (e.g., schizophrenia) in patient or caregiver as determined by medical chart review BEHAVIORAL: SMART@Home
Asthma, Asthma in Children
Asthma
A Study Using Nivolumab, in Combination With Chemotherapy Drugs to Treat Nasopharyngeal Carcinoma (NPC)
- cancer@cchmc.org
ALL
Up to 21 years old
PHASE2
NCT06064097
Inclusion Criteria:
* Patients must be ≤ 21 years of age at the time of study enrollment
* Newly diagnosed American Joint Committee on Cancer (AJCC) stage II-IV nasopharyngeal carcinoma (NPC)
* Patients must have had histologic verification of the malignancy at original diagnosis
* Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended
* Patients must have had histologic verification of the malignancy at original diagnosis
* Although submission of tumor tissue for the molecular characterization initiative is not required for eligibility, it is strongly recommended
* Patients must have a Lansky (for patients ≤ 16 years of age) or Karnofsky (for patients \> 16 years of age) performance status score of ≥ 60%
* Peripheral absolute neutrophil count (ANC) ≥ 1000/uL (within 7 days prior to start of protocol therapy)
* Platelet count ≥ 100,000/uL (transfusion independent) (within 7 days prior to start of protocol therapy)
* Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2 or (within 7 days prior to start of protocol therapy)
* A serum creatinine based on age/sex (within 7 days prior to start of protocol therapy) Age: Maximum serum creatinine (mg/dL)
1 month to \< 6 months: 0.4 mg/dL (male); 0.4 mg/dL (female) 6 months to \< 1 year: 0.5 mg/dL (male); 0.5 mg/dL (female)
1 to \< 2 years: 0.6 mg/dL (male); 0.6 mg/dL (female) 2 to \< 6 years: 0.8 mg/dL (male); 0.8 mg/dL (female) 6 to \< 10 years 1 mg/dL (male); 1 mg/dL (female) 10 to \<13 years: 1.2 mg/dL (male); 1.2 mg/dL (female) 13 to \< 16 years: 1.5 mg/dL (male); 1.4 mg/dL (female)
≥ 16 years: 1.7 mg/dL (male); 1.4 mg/dL (female)
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age, and (within 7 days prior to start of protocol therapy)
* Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) ≤ 135 U/L\* (within 7 days prior to start of protocol therapy)
* Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
* Shortening fraction of ≥ 27% by echocardiogram, or
* Ejection fraction of ≥ 50% by radionuclide angiogram
* No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry \> 94% if there is clinical indication for determination
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months and T-cell count above the lower limit of normal are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
Exclusion Criteria:
* Patients who received prior radiotherapy to the head or neck
* Patients who received prior chemotherapy or radiation for the treatment of any cancer in the last 3 years. These patients must also be in remission
* Patients with a diagnosis of immunodeficiency
* Patients with an active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive agents). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
* Note: Patients with well-controlled asthma and no need for systemic steroids for the treatment of asthma in the last 12 months will not be excluded
* Patients with a condition requiring systemic treatment with either corticosteroids (\> 0.25 mg/kg (10 mg) daily prednisone equivalent) within 14 days or other immunosuppressive medications within 30 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 0.25 mg/kg (10 mg) daily prednisone equivalent, are permitted in the absence of active autoimmune disease
* Patients with a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
* Patients with detectable viral load of human immunodeficiency virus (HIV), hepatitis B or hepatitis C, or active tuberculosis
* Patients who have undergone solid organ or allogeneic hematopoietic transplant at any time
* Due to risks of fetal and teratogenic adverse events as seen in animal studies, a negative pregnancy test must be obtained in females of childbearing potential, defined as females who are post-menarchal. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
* Females of childbearing potential that are sexually active must agree to either practice 2 medically accepted highly-effective methods of contraception at the same time or abstain from heterosexual intercourse from the time of signing the informed consent through 5 months after the last dose of nivolumab, 6 months after the last dose of gemcitabine, and 14 months after the last dose of cisplatin, whichever is longer
* Males of childbearing potential that are sexually active must agree to either practice a medically accepted highly-effective methods of contraception or abstain from heterosexual intercourse from the time of signing the informed consent through 3 months after the last dose of gemcitabine, and 11 months after the last dose of cisplatin, whichever is longer
* Lactating females are not eligible unless they have agreed not to breastfeed their infants starting with the first dose of study therapy through 5 months after the last dose of nivolumab
* All patients and/or their parents or legal guardians must sign a written informed consent
* All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met OTHER: Questionnaire Administration, PROCEDURE: Biopsy Procedure, PROCEDURE: Biospecimen Collection, PROCEDURE: Chest Radiography, DRUG: Cisplatin, PROCEDURE: Computed Tomography, PROCEDURE: Echocardiography Test, OTHER: Electronic Health Record Review, OTHER: Fluciclovine F18, DRUG: Gemcitabine, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, BIOLOGICAL: Nivolumab, PROCEDURE: Positron Emission Tomography, OTHER: Quality-of-Life Assessment, RADIATION: Radiation Therapy, PROCEDURE: X-Ray Imaging
Stage II Nasopharyngeal Carcinoma AJCC v8, Stage III Nasopharyngeal Carcinoma AJCC v8, Stage IV Nasopharyngeal Carcinoma AJCC v8
Study to Evaluate the Efficacy and Safety of BMN 333 Versus Vosoritide in Children With Achondroplasia (ASPEN)
Racheal Powers - Racheal.Powers@cchmc.org
ALL
2 years to 17 years old
PHASE2
NCT07441876
Inclusion Criteria:
• Participants must be aged ≥ 2 to \< 11 years (Phase 2) or ≥ 2 to \< 18 years (Phase 3), at the time of signing the informed consent
• Participants must have ACH (confirmed by documented genetic testing) and open epiphyses
• Are Tanner Stage I (Phase 2) or any Tanner stage (Phase 3)
• Are ambulatory and able to stand without assistance
Exclusion Criteria:
• Have any short stature condition other than ACH (eg, hypochondroplasia, trisomy 21, pseudoachondroplasia, GH deficiency)
• Have any of the following disorders: Hypothyroidism or hyperthyroidism, unless treated with evidence of normalized thyroid-stimulating hormone (TSH) levels, diabetes mellitus, unless considered well-controlled, autoimmune inflammatory disease, inflammatory bowel disease, autonomic neuropathy, anemia defined as hemoglobin \< 10 g/dL, vitamin D deficiency, significant hip pathology.
• Have history of any renal insufficiency or cardiac/ cardiovascular disease that places the participant at increased risk of an adverse cardiac outcome in the setting of hypotension.
• Have had bone fractures of the long bones or spine within 6 months prior to screening.
• Have used vosoritide, any other approved product (except GH, as detailed below), investigational product, or investigational medical device for the treatment of ACH or short stature at any time
• Have been treated with GH, insulin-like growth factor 1, or anabolic steroids in the 6 months prior to treatment start
DRUG: BMN 333, DRUG: Vosoritide Injection [Voxzogo]
Achondroplasia
Achondroplasia, ACH, Bone Diseases, Developmental Dwarfism, Bone Diseases, Genetic Diseases, Inborn, Musculoskeletal Diseases, Natriuretic Peptide, C-type, Osteochondrodysplasias, Physiological Effects of Drugs, Skeletal Dysplasias
Bowel Continence Across the Lifespan in People With Spina Bifida (BCALS)
Cassie Hulme - cassie.hulme@cchmc.org
ALL
5 years and over
NCT07390318
Inclusion Criteria:
* Minimum age 5 years old
* Myelomeningocele diagnosis
* Starting a retrograde or antegrade enema program (or switching from one enema program to the other)
* English or Spanish speaking/literate
Exclusion Criteria:
\- Other types of spinal dysraphism (e.g., lipomyelomeningocele, fatty filum) PROCEDURE: Retrograde Enema, PROCEDURE: Antegrade Enema
Spina Bifida, Neurogenic Bowel, Bowel Incontinence
retrograde enema, antegrade enema, bowel management program, bowel continence program, self-management, quality of life
Neuroblastoma Biology Study
- cancer@cchmc.org
ALL
31 days to 99 years old
NCT01587300
Inclusion Criteria:
* Patients must be greater than or 31 days of age.
* Patients must have had a diagnosis of high risk neuroblastoma either by histological verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
* All patients with refractory or recurrent high risk neuroblastoma at NANT institutions are eligible regardless of disease status (including no measurable or evaluable tumor) as long as they undergo a disease evaluation and appropriate samples are submitted.
* Additionally, all patients with high risk neuroblastoma without relapse treated at a NANT institution are eligible if undergoing a disease evaluation, as long as Children's Oncology Group specimens are prioritized.
Exclusion Criteria:
* There are no exclusion criteria on this study. Neuroblastoma
A Pilot Study of Larotrectinib for Newly-Diagnosed High-Grade Glioma With NTRK Fusion
- cancer@cchmc.org
ALL
Up to 21 years old
EARLY_PHASE1
NCT04655404
Inclusion Criteria:
* Age: Patients ≤ 21 years of age (birth to 21 years of age) at the time of study enrollment will be eligible.
* Diagnosis: Patients with newly-diagnosed high-grade (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors are documented in a CLIA/CAP certified lab (or clinically equivalent method considered standard in non-US sites) to harbor an NTRK fusion alteration by FISH, PCR, or next generation sequencing are eligible. Patients must have had histologically verified high-grade glioma such as anaplastic astrocytoma, glioblastoma, or H3 K27-mutant diffuse midline glioma verified at a CONNECT site.
For sites that do not have CLIA-certified equivalent (certified laboratory) to assess NTRK fusion, testing will be conducted centrally at NCH. NTRK testing will be performed by NGS using targeted RNA-sequencing (Archer Solid Tumor analysis) Please submit 10 unstained sections on charged slides at 10uM thickness, or 10 scrolls cut at 10uM thickness, along with submission of an H\&E slide. Formalin-fixed paraffin embedded (FFPE) tissue block and FFPE tissue scroll specimens must contain minimum of 25% tumor Snap-frozen tissue specimens are also acceptable and they must contain a minimum of 10% tumor. Please note that turn-around time for this test is up to 21 days.
* Disease Status: Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e. no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented NTRK fusion, must be discussed with the Study Chair on a case-by-case basis.
* Surgical Cohort ONLY: Patients with newly-diagnosed HGG with NTRK fusions who have undergone prior biopsy and for whom further resection is indicated for a more definitive surgery at an enrolling site will be eligible to enroll onto the surgical study. DIPG patients are not eligible for the surgical cohort.
* Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
* Prior Therapy: Patients must not have received any prior anti-cancer chemotherapy. Prior use of corticosteroids are allowed (see below Exclusion Criteria)
* Organ Function Requirements: Adequate Bone Marrow Function Defined as:
Peripheral absolute neutrophil count (ANC) ≥ 1000/mm3 Platelet count ≥ 100,000/mm3 (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) Hemoglobin \>8 g/dL (may receive transfusions)
\- Adequate Renal Function Defined as: Serum creatinine within normal institutional limits, or Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2
\- Adequate Liver Function Defined as: Total bilirubin ≤ 2.5 × institutional upper limit of normal AST(SGOT)/ALT(SGPT) ≤ 2.5 × institutional upper limit of normal
\- Adequate Pulmonary Function Defined as: Pulse oximetry \> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).
\- Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled. See Section 5.5.2 and Appendix III for EIAED guidelines.
\- Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
Exclusion Criteria:
* Pregnancy or Breast-Feeding: Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
* Concomitant Medications Investigational Drugs: Patients who have previously received or are currently receiving another investigational drug are not eligible.
Anti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible
* Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.
* Patients who have received prior solid organ transplantation are not eligible.
* Patients must not have malabsorption syndrome or other condition affecting oral absorption.
* Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. (See Appendix III.) Strong inducers or inhibitors of CYP3A4 should be avoided from 7 days prior to enrollment to the end of the study.
* Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible. DRUG: Larotrectinib, PROCEDURE: Larotrectinib surgical
High Grade Glioma, Diffuse Intrinsic Pontine Glioma
NTRK gene fusion, BABYPOG, HIT-SKK, Larotrectinib
A Study of DB-OTO, an Adeno-Associated Virus (AAV) Based Gene Therapy, in Children/Infants, Adolescents and Adults With Hearing Loss Due to Otoferlin Mutations (CHORD)
Elizabeth Dolgas - elizabeth.dolgas@cchmc.org
ALL
PHASE1
NCT05788536
Key
• Willingness to provide written informed consent (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) and willingness to comply with trial protocol
• Willingness to consent to genetic testing for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in order to evaluate a panel of hearing loss-related genes
• Willingness to consent to vaccinations for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in accordance with the country-specific, age-appropriate immunization schedule, as described in the protocol
• Participant able to perform all necessary assessments to qualify for enrollment and dosing in the corresponding cohort at the time the participant or parent/legal guardian signing the informed consent form (and participant providing assent, when applicable)
• Presence of biallelic, likely pathogenic or pathogenic OTOF variants
• No clinically significant laboratory findings on clinical laboratory tests at time of Screening as described in the protocol
• Audiological Criteria:
• Investigator diagnoses the participant with profound sensorineural hearing loss (SNHL; \>90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function
• Outer hair cell presence is confirmed via presence of otoacoustic emissions (≥6 dBSNR) at ≥3 frequencies from 1 to 8 kHz in the ear(s) to be infused with DB-OTO. Alternatively, for participants \>24 months of age, outer hair cell presence can be confirmed via presence of the cochlear microphonic in the ear(s) to be infused with DB-OTO.
• No evidence from measures of hearing loss that show a dependence on body temperature
• From study start and for the duration of the short-term follow-up period (48 weeks): Female participants of childbearing potential and fertile males, must agree to use highly effective contraception. Female participants must agree not to become pregnant. Fertile male participants must agree not to father a child or donate sperm, for 48 weeks and in cases of early withdrawal, for at least 12 months after DB-OTO administration. Key
• History of prior treatment with gene therapy
• Surgical anatomy that would preclude or meaningfully impact the planned surgical approach as indicated by medical imaging (eg, Computed Tomography \[CT\] or Magnetic Resonance Imaging \[MRI\]) in the ear(s) to be infused with DB-OTO
• History or presence of other permanent or untreatable hearing loss conditions
• Prior or current history of malignancies
• Prior or current history of meningitis
• History or presence of cochlear implants in the ear(s) to be infused with DB-OTO
• History of risk factor(s) for auditory neuropathy not caused by OTOF pathogenic variants including but not limited to: prematurity, low birth weight, hyperbilirubinemia, Neonatal Intensive Care Unit (NICU) admission, and/or low Apgar scores as described in the protocol Note: Other protocol-defined inclusion/exclusion criteria apply
Inclusion Criteria:
• Willingness to provide written informed consent (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) and willingness to comply with trial protocol
• Willingness to consent to genetic testing for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in order to evaluate a panel of hearing loss-related genes
• Willingness to consent to vaccinations for the participant (by at least one parent/legal guardian for pediatric participants, and with participant to provide assent, when applicable, or by the adult participant) in accordance with the country-specific, age-appropriate immunization schedule, as described in the protocol
• Participant able to perform all necessary assessments to qualify for enrollment and dosing in the corresponding cohort at the time the participant or parent/legal guardian signing the informed consent form (and participant providing assent, when applicable)
• Presence of biallelic, likely pathogenic or pathogenic OTOF variants
• No clinically significant laboratory findings on clinical laboratory tests at time of Screening as described in the protocol
• Audiological Criteria:
• Investigator diagnoses the participant with profound sensorineural hearing loss (SNHL; \>90 dB HL) based on behavioral and physiologic measurements (ABR) of inner ear function
• Outer hair cell presence is confirmed via presence of otoacoustic emissions (≥6 dBSNR) at ≥3 frequencies from 1 to 8 kHz in the ear(s) to be infused with DB-OTO. Alternatively, for participants \>24 months of age, outer hair cell presence can be confirmed via presence of the cochlear microphonic in the ear(s) to be infused with DB-OTO.
• No evidence from measures of hearing loss that show a dependence on body temperature
• From study start and for the duration of the short-term follow-up period (48 weeks): Female participants of childbearing potential and fertile males, must agree to use highly effective contraception. Female participants must agree not to become pregnant. Fertile male participants must agree not to father a child or donate sperm, for 48 weeks and in cases of early withdrawal, for at least 12 months after DB-OTO administration. Key
Exclusion Criteria:
• History of prior treatment with gene therapy
• Surgical anatomy that would preclude or meaningfully impact the planned surgical approach as indicated by medical imaging (eg, Computed Tomography \[CT\] or Magnetic Resonance Imaging \[MRI\]) in the ear(s) to be infused with DB-OTO
• History or presence of other permanent or untreatable hearing loss conditions
• Prior or current history of malignancies
• Prior or current history of meningitis
• History or presence of cochlear implants in the ear(s) to be infused with DB-OTO
• History of risk factor(s) for auditory neuropathy not caused by OTOF pathogenic variants including but not limited to: prematurity, low birth weight, hyperbilirubinemia, Neonatal Intensive Care Unit (NICU) admission, and/or low Apgar scores as described in the protocol Note: Other protocol-defined inclusion/exclusion criteria apply
GENETIC: DB-OTO
Congenital Hearing Loss Secondary to Biallelic Mutations of the Otoferlin Gene (OTOF)
DB-OTO, Gene Therapy, Congenital Hearing Loss, Sensorineural Hearing Loss, Auditory Neuropathy, Pediatric, Cochlear Implant, Otoferlin, Deaf, Hard of hearing, Hearing impaired, Hearing disorder, Fully implantable hearing aid, Child, Infant, Adolescents, Young Adults, Adults, CHORD