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340 Study Matches
A Tailored Medication Adherence-Promotion Intervention for Adolescents and Young Adults With Cancer
- meghan.mcgrady@cchmc.org
ALL
15 years to 24 years old
NA
NCT07223463
Inclusion Criteria:
* Patient is 15.00 to 24.99 years of age
* Patient is diagnosed with cancer
* Patient is prescribed an oral anticancer/antitumor agent or prophylaxis
Exclusion Criteria:
* Patient is not fluent in English
* Patient evidences significant cognitive deficits
* Patient's medical status or treatment precludes participation
* Patient enrolled on a medical trial requiring medication storage in a trial-provided container
* Patient demonstrates greater than or equal to 95% adherence during run-in period
* Patient declines to use or has difficulty using electronic adherence monitoring device during run-in BEHAVIORAL: Tailored Program, BEHAVIORAL: Feedback Program (Uniform Standard of Care)
Cancer, Medication Adherence
adolescents and young adults, cancer, adherence
Feto-Endoscopic Tracheal Occlusion (FETO) for Severe Congenital Diaphragmatic Hernia (FETO)
Madeline Peters - madeline.peters@cchmc.org
FEMALE
18 years to 50 years old
NA
NCT02986087
Inclusion Criteria:
* Isolated CDH with liver up
* Severe pulmonary hypoplasia with ultrasound O/E LHR \<25% at the time of surgery
* Gestational age at FETO procedure 27 weeks 0 days to 29 weeks 6 days
* Moderate pulmonary hypoplasia with ultrasound O/E LHR \<30% and liver-up at the time of surgery
* Gestational age at FETO procedure 30 weeks 0 days to 31 weeks 6 days in this moderate category
* Maternal age greater than or equal to 18 years
* Gestational age at enrollment prior to 29 weeks 6 days, or 31 weeks 6 days in moderate category
* Normal karyotype or FISH
* Normal fetal echocardiogram
* Singleton pregnancy
* Willing to remain in the greater Cincinnati area for remainder of pregnancy
* Family considered and decline option of termination of the pregnancy at less than 24 weeks 0 days
* Family meets psychosocial criteria
Exclusion Criteria:
* Patient \< 18 years old
* Multi-fetal pregnancy
* Rubber latex allergy
* Preterm labor, cervix shortened (\<15 mm) or uterine anomaly strongly predisposing to preterm labor, placenta previa
* Bilateral CDH, isolated left sided CDH with an O/E \> 30%
* Additional fetal anomaly by ultrasound, MRI, or echocardiogram
* Chromosomal abnormalities
* Maternal contraindications to fetoscopic surgery or severe maternal condition in pregnancy
* Incompetent cervix with or without a cerclage
* Placental abnormalities known at time of enrollment
* Maternal HIV, Hepatits B, Hepatitis C
* Maternal uterine anomaly
* 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: Fetal Tracheal Occlusion
Congenital Diaphragmatic Hernia, Pulmonary Hypoplasia, Pulmonary, Hypertension
A Study to Assess Growth in Children With Idiopathic Short Stature
Cierra Farrell - cierra.farrell@cchmc.org
ALL
2 years to 16 years old
NCT06309979
Inclusion Criteria:
• Participants must be \> 2 years old, and ≤ 14 years old (female) or ≤ 16 years old (males) at the time of signing the informed consent.
• A height assessment corresponding to a height Z-score of ≤ -2.25 SDs in reference to the general population of the same age and sex, as calculated using the Centers for Disease Control and Prevention (CDC) growth chart (https://www.cdc.gov/growthcharts/zscore.htm).
• Participants who have either never received hGH, or who are currently receiving hGH treatment.
• Historic stimulation test result with serum or plasma GH level greater than 10 μg/L.
• Parent(s) or guardian(s) are willing and able to provide written, signed informed consent.
Exclusion Criteria:
• Diagnosis of systemic disease or condition that may cause short stature, eg renal, neoplastic, pulmonary, cardiac, gastrointestinal, immunologic and metabolic disease. Children with such diagnoses can be considered for inclusion if their condition is well controlled, at the discretion of the Medical Monitor.
• Known presence of one or more pituitary hormone deficiencies
• Bone age advanced over chronological age by more than 3 years.
• For hGH naïve participants, historic stimulation test result with serum or plasma GH level greater than 10 μg/L or serum IGF-1 in the normal range for age (between -1.00 SDs and +2.00 SDs).
• For participants currently on hGH treatment, historic results before GH treatment of stimulation test with serum or plasma GH level greater than 10 μg/L or serum IGF-1 test between -1.00 SDs and +2.00 SDs.
• Have received an investigational product (IP) or investigational medical device for any purpose within 6 months before the Screening visit. .
Idiopathic Short Stature
International Diffuse Intrinsic Pontine Glioma (DIPG)/Diffuse Midline Glioma (DMG) Registry and Repository
- referrals@dipgregistry.org
ALL
NCT03101813
Inclusion Criteria:
* All patients of any age (living or deceased) with a diagnosis (either current or past) of a DIPG/DMG tumor
* Unless the patient is deceased, all patients and/or one parent or legal guardian must provide written informed consent as well as HIPAA/release of information consent. Diffuse Intrinsic Pontine Glioma, Diffuse Midline Glioma, H3 K27M-Mutant, Diffuse Midline Glioma
Study of Oral Food Challenge Biomarkers (SAFER) (SAFER)
Jenn Jennings - jennifer.jennings2@cchmc.org
ALL
12 months to 17 years old
NCT07279467
Inclusion Criteria:
• Parent or guardian must be able to understand and provide written informed consent and participant must be able to understand and provide assent (if applicable)
• Are 12 months - 17 years of age during Screening.
• Are sensitized to peanut, as demonstrated by one of the following: a. A participant-reported reaction to peanut (at any time) deemed by the investigator to be consistent with an IgE-mediated reaction and one of the following within the past 12 months i. Positive Skin Prick Test (SPT) to peanut (wheal diameter that is ≥ 3mm larger than saline control) ii. Positive peanut-specific IgE (sIgE; ≥ 0.10 kUA/L) determined by ImmunoCap b. An Ara h 2 sIgE ≥ 1.0 kUA/L, measured within the past 12 months
• Are currently avoiding peanut
Exclusion Criteria:
• Are pregnant
• Are currently receiving treatment or have received treatment within the prior 2 years for peanut allergy
• Have a history of life-threatening anaphylaxis to peanut, defined as neurological compromise or requiring intubation
• Have received treatment with dupilumab/Dupixent® within the prior 2 years, OR treatment with omalizumab/Xolair®, other biologics, or systemic immunomodulatory agents within the prior year
• Inability to comply with the required aspects of the study protocol
• Have past or current medical conditions or findings from the physical examination, not already listed, that, in the judgment of the site investigator, may pose additional risks related to participation in the study, interfere with the participant's ability to comply with study requirements, or impact the quality or interpretation of the study data
• Have been treated with oral steroid or beta blockers within 14 days of the Oral Food Challenge (OFC)
• Are unable to discontinue medications, as specified in the Protocol CoFAR-15 MOP, for the minimum wash-out periods prior to Skin Prick Test (SPT) or OFC
• Have poorly controlled atopic dermatitis (AD) at Screening, per the PI's discretion
• Have poorly controlled or severe asthma/wheezing at Screening, as defined as experiencing or including any of the following:
• Meeting the Global Initiative for Asthma (GINA) criteria for uncontrolled asthma
• History of two or more systemic corticosteroid courses within six months of Screening or one course of systemic corticosteroids within three months of Screening to treat asthma/wheezing;
• Prior intubation/mechanical ventilation for asthma/wheezing;
• One hospitalization or ED visit for asthma/wheezing within six months of Screening;
• Forced expiratory volume in one second (FEV1) \<80% of predicted or FEV1/forced vital capacity (FVC) \<75% of predicted, with or without controller medications (only for participants who are aged seven years or older and are able to perform spirometry);
• Inhaled corticosteroid (ICS) dosing of \>500 mcg daily fluticasone (or equivalent ICS based on the CoFAR Inhaled Corticosteroid Equivalency Tables MOP)
• Refuse blood sample collection during Screening
• The SPT performed during Screening is negative to peanut allergen without dilution (wheal diameter that is \< 3mm larger than saline control).
DRUG: Oral Food Challenge (OFC): Peanut Protein
Allergy
Food Allergy, Peanut Allergy, Oral Food Challenge, CoFAR-15, SAFER, Biomarkers
A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-cell Acute Lymphoblastic Leukemia (B-ALL)
- cancer@cchmc.org
ALL
366 days to 46 years old
PHASE2
NCT06124157
Inclusion Criteria:
* Patients must be \> 365 days and \< 18 years (for AIEOP-BFM), \> 365 days and \< 22 years (for Children's Oncology Group \[COG\]) and \> 365 days and \< 46 years (for ALLTogether sites) at the time of enrollment
* Newly-diagnosed Ph+ or ABL-class Ph-like B-ALL. Leukemic blasts must express CD19. ABL-class fusions are defined as rearrangements involving the following genes predicted to be sensitive to imatinib and/or dasatinib: ABL1, ABL2, CSF1R, and PDGFRB
* Evidence of BCR::ABL1 should be documented by a clinically-validated assay prior to study entry on day 15 from the first dose of vinCRIStine during Induction therapy. ABL-class Ph-like B-ALL gene rearrangements should be documented by a clinically-validated assay and enrolled on study by day 1 of Blinatumomab Block 1. Accepted methods of detection include fluorescence in situ hybridization (FISH) using break-apart of colocalization signal probes, singleplex or multiplex reverse-transcription polymerase chain reaction (RT-PCR), whole-transcriptome or panel-based ribonucleic acid (RNA) sequencing (e.g., Hematologic Cancer Fusion Analysis, TruSight RNA Pan-Cancer Panel or equivalent). Confirmation of 5' fusion partner genes is not required for study enrollment
* Patients with Ph+ B-ALL must have previously started Induction therapy, which includes vinCRIStine, a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline, and/or other standard cytotoxic chemotherapy
* Patients with Ph+ B-ALL have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vinCRIStine
* Patients with ABL-class Ph-like B-ALL must have previously completed 4 or 5 weeks of multiagent Induction chemotherapy (Induction 1A)
* Patients may have started either imatinib or dasatinib prior to study entry but should have received no more than 14 days of TKI for Ph+ B-ALL or no more than 35 days of TKI for ABL-class Ph-like B-ALL
* Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of ≤ 2 or Karnofsky and Lansky performance scores ≥ 50%. Use Karnofsky for patients \> 16 years of age and Lansky for patients ≤ 16 years of age
* For pediatric patients (age 1-17 years): a glomerular filtration rate (GFR) ≥ 50 mL/min/1.73 m\^2, as determined by one of the following methods (must be performed within 7 days prior to enrollment unless otherwise indicated):
* Estimated GFR (eGFR) ≥ 50 mL/min/1.73 m2
* Measured GFR ≥ 50 mL/min/1.73 m\^2 (any age). If measured GFR is used, it must be performed using direct measurement with a nuclear blood sampling method or small molecule clearance method (iothalamate or other molecule per institutional standard
* For adult patients (age 18 years or older): Creatinine clearance ≥ 30 mL/min, as estimated by the Cockcroft and Gault formula. The creatinine value used in the calculation must have been obtained within 28 days prior to registration. Estimated creatinine clearance is based on body weight
* Direct bilirubin \< 2.0 mg/dL (34.2 micromoles/L) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 10 x upper limit of normal (ULN) (must be performed within 7 days prior to enrollment unless otherwise indicated)
* \* Shortening fraction of ≥ 27% by echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) OR
* Left Ventricular Ejection fraction of ≥ 50% by radionuclide angiogram or echocardiogram (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\]) AND
* Corrected QT Interval, QTc \< 480mSec (must be obtained within 21 days prior to enrollment and start of protocol therapy \[repeat if necessary\])
* Note: Repeat echocardiogram and electrocardiogram are not required if they were performed at or after initial ALL diagnosis before study enrollment
Exclusion Criteria:
* Known history of chronic myeloid leukemia (CML)
* ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase
* ALL developing after a previous cancer treated with cytotoxic chemotherapy
* Active, uncontrolled infection or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
* Down syndrome (trisomy 21)
* Pregnancy and breast feeding
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A negative pregnancy test is required for female patients of childbearing potential within 7 days prior to enrollment
* Lactating females who plan to breastfeed their infants
* Sexually active male and female patients of reproductive potential who have not agreed to use an effective contraception method for the duration of treatment according to protocol
* NOTE: Patients who could become pregnant or could father a child must use effective contraception during protocol treatment and for 30 days after the last dose of dasatinib or 14 days after the last dose of imatinib dose or per institutional standard of care for multiagent chemotherapy, whichever is longer
* Prior treatment with TKIs before study entry with the exception of imatinib or dasatinib
* Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block
* Patients with known Charcot-Marie-Tooth disease
* Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with central nervous system (CNS) involvement
* Note: Patients with a history of seizures that are well controlled on stable doses of anti-epileptic drugs are eligible. Patients with a history of cerebrovascular ischemia/hemorrhage with residual deficits are not eligible. Patients with a history of cerebrovascular ischemia/hemorrhage remain eligible provided all neurologic deficits have resolved
* HIV-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of treatment
* 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 PROCEDURE: Biospecimen Collection, BIOLOGICAL: Blinatumomab, PROCEDURE: Bone Marrow Biopsy, DRUG: Calaspargase Pegol, DRUG: Cyclophosphamide, DRUG: Cytarabine, DRUG: Dasatinib, DRUG: Daunorubicin, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Imatinib, DRUG: Leucovorin, DRUG: Mercaptopurine, DRUG: Methotrexate, PROCEDURE: Multigated Acquisition Scan, DRUG: Pegaspargase, DRUG: Prednisolone, DRUG: Prednisone, RADIATION: Radiation Therapy, DRUG: Thioguanine, DRUG: Vincristine
B Acute Lymphoblastic Leukemia
Study to Evaluate Biological & Clinical Effects of Significantly Corrected CFTR Function in Infants & Young Children (BEGIN)
Kelly Thornton - kelly.thornton@cchmc.org
ALL
Up to 10 years old
NCT04509050
Inclusion Criteria:
* Part A:
* Less than 10 years of age at the first study visit.
* Documentation of a CF diagnosis.
Part B:
* Participated in Part A OR less than 7 years of age at the first study visit.
* Documentation of a CF diagnosis.
* CFTR mutations consistent with FDA labeled indication of highly effective modulator therapy (ivacaftor or elexacaftor/tezacaftor/ivacaftor).
* Physician intent to prescribe ivacaftor or elexacaftor/tezacaftor/ivacaftor.
Exclusion Criteria:
* Part A and Part B:
* Use of an investigational drug within 28 days prior to and including the first study visit.
* Use of ivacaftor or elexacaftor/tezacaftor/ivacaftor within the 28 days prior to and including the first study visit.
* Use of chronic oral corticosteroids within the 28 days prior to and including the first study visit. DRUG: Ivacaftor or elexacaftor/tezacaftor/ivacaftor
Cystic Fibrosis
Cystic Fibrosis, CF, CFTR Modulator, triple combination therapy, elexacaftor, tezacaftor, ivacaftor
Registry Study to Observe Long-term Safety of Vamorolone (AGAMREE®) in Patients With Duchenne Muscular Dystrophy-SUMMIT (DMD-001 SUMMIT)
Cuixia Tian, MD - Cuixia.Tian@cchmc.org
MALE
2 years and over
NCT06564974
Inclusion Criteria:
• Patient or parent/legal guardian is willing and able to provide written informed consent once the nature of the registry has been explained and prior to the start of any registry-related procedures.
• Patient and/or parent/guardian are willing and able to complete QoL questionnaires.
• Male patients at least 2 years old.
• Confirmed diagnosis of DMD (via genetic testing or muscle biopsy with absent dystrophin staining to anti- dystrophin antibodies 3, 1, or 2, or dystrophin immunohistochemistry or western blot).
• Patient has a current, active prescription for, or is on, AGAMREE®.
Exclusion Criteria:
1\. Any contraindication to AGAMREE® or medical condition, which, in the opinion of the Investigator, would affect registry participation, performance, or interpretation of registry assessments. DRUG: Vamorolone
Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy, Neuromuscular, AGAMREE®, Vamorolone, DMD, Muscular Dystrophy
Observation Study in Patients Age 0-5 Years With LAMA2-related Congenital Muscular Dystrophy
Jessica Getz - Jessica.getz@cchmc.org
ALL
Up to 5 years old
NCT06503367
Inclusion Criteria:
* Signed informed consent by the subject, parent(s) or legally authorized representative (LAR) and/or assent by the subject (when applicable).
* Subject must be aged birth to less than 5.0 years of age at time of consent.
* A confirmed diagnosis of LAMA2-RD confirmed via:
a: Two pathogenic variants in the LAMA2 gene (via a CLIA-approved laboratory) or: b. muscle biopsy with absence of merosin (laminin-211) and at least one pathogenic variant in the LAMA2 gene
* Absence of another confirmed genetic disease.
* Willingness to maintain current exercise and/or physical therapy regimen for the duration of the clinical study.
* Willingness to comply with the study protocol, including but not limited to, all study procedures and visits.
Exclusion Criteria:
* Acute medical illness or hospitalization within 30 days prior to informed consent.
* Participation in a previous trial of any investigational agent for LAMA2-RD within 1 month prior to informed consent, or use of any other investigational therapy (including off-label use of Losartan) within 30 days prior to informed consent, or participation in other clinical studies, within 30 days (or 3 half-lives, whichever is longer) prior to informed consent, which in the opinion of the PI, may potentially confound results from this study.
* Other significant medical condition, which in the opinion of the site Principal Investigator may confound interpretation of the clinical course of LAMA2- RD. LAMA2-MD \(Merosin Deficient Congenital Muscular Dystrophy, MDC1A\)
Early Phase 1, Observational, Natural History, Neuromuscular, Functional Assessments
RASopathy Biorepository
Lindsey Aschbacher-Smith - lindsey.aschbacher-smith@cchmc.org
ALL
NCT04395495
Inclusion Criteria:
* Patients with a suspected or known diagnosis of any of the group of disorders known as RASopathies (e.g., Neurofibromatosis, Costello Syndrome, Noonan Syndrome). Diagnosis may be made clinically and/or confirmed through genetic testing.
* Unaffected relatives of patients with a suspected or known diagnosis of any of the group of disorders known as RASopathies.
Exclusion Criteria:
* Individuals who do not have a suspected or definite diagnosis of a RASopathy.
* Individuals who do not have a relative with a suspected or definite diagnosis of a RASopathy.
* Patients who do not have the ability/capacity to undergo the informed consent process OR whose parent/legal guardian is unable to undergo the informed consent process. RAS Mutation, Neurofibromatosis 1, Noonan Syndrome, Noonan Syndrome With Multiple Lentigines, Noonan Neurofibromatosis Syndrome, Cardiofaciocutaneous Syndrome, Costello Syndrome, Legius Syndrome, Smith-Kingsmore Syndrome, MTOR Gene Mutation, GATOR-1 Gene Mutation, SYNGAP1-Related Intellectual Disability, DLG4, MAPK1 Gene Mutation
A Clinical Study of Letermovir (MK-8228) in Children and Adolescents Who Receive a Kidney Transplant (KT) (MK-8228-077)
Caitlin Brammer - caitlin.brammer@cchmc.org
ALL
Up to 17 years old
PHASE1
NCT07199465
Inclusion Criteria:
The main inclusion criteria include but are not limited to the following:
* Is a recipient of a primary or secondary allograft kidney
* Is at least 4 weeks posttransplant and not more than 52 weeks posttransplant at the time of enrollment (Day 1) and is being managed per local standard of care
* Has stable kidney function posttransplant
* Has undetectable CMV deoxyribonucleic acid (DNA) from a plasma or whole blood sample collected within 14 days prior to enrollment
* Must be able to take (as assessed by the investigator) letermovir tablets or oral pellets by mouth, or via gastrostomy or nasogastric tube (oral pellets only)
* Does not have a condition that may interfere with the absorption of oral medication (e.g., vomiting, diarrhea, or a malabsorptive condition) from the day of enrollment (Day 1) until the intensive pharmacokinetics (IPK) sampling is completed
* Weighs ≥2.5 and \<40 kg at enrollment (Day 1)
Exclusion Criteria:
The main exclusion criteria include but are not limited to the following:
* Has CMV disease or suspected CMV disease between screening and enrollment
* Is on dialysis or plasmapheresis at the time of enrollment
* Has evidence of CMV viremia at any time from screening until the time of enrollment
* Has Child-Pugh B or C hepatic insufficiency within 14 days before enrollment
* Is a multi-organ transplant recipient (e.g., kidney-pancreas)
* Has any uncontrolled infection on the day of enrollment
* Requires mechanical ventilation, or is hemodynamically unstable, at the time of enrollment
* Has received or is receiving protocol-specified prohibited medications DRUG: Letermovir
Cytomegalovirus Prophylaxis
A Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia
- cancer@cchmc.org
ALL
29 days to 21 years old
PHASE2
NCT05955261
Patients with preexisting conditions that may affect chemotherapy tolerance (e.g., bone marrow failure syndrome, cardiac disease, pulmonary disease, and history of significant hepatic impairment) should be discussed with study PI in detail to enable review of the medical history prior to enrollment onto AML23 study.
Inclusion Criteria:
* Diagnosis of AML fulfilling the criteria of the WHO classification of myeloid neoplasms or \< 20% marrow myeloblasts and evidence of a clonal de novo AML genetic abnormality or myeloid sarcoma or primary myelodysplastic syndrome (MDS) with ≥ 10% blasts or a complete blood count with the presence of at least 1,000 blasts/μL (e.g., a WBC count ≥ 10,000/μL with ≥ 10% blasts or a WBC count ≥ 5,000/μL with ≥ 20% blasts
* Age \> 28 days and \< 22 years
* No prior therapy for this malignancy except for one dose of intrathecal therapy and hydroxyurea or low-dose cytarabine (≤ 200 mg/m\^2 per day for ≤ 7 days)
* Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment
* Male and female participants of reproductive potential must agree to use an effective contraceptive method during the study and for 6 months after study treatment
* Written informed consent from the patient and/or parent/legal guardian
* Direct bilirubin ≤ 1.5 x institutional upper limit of normal
Exclusion Criteria:
* Patients with treatment-related AML, Down syndrome, acute promyelocytic leukemia, chronic myeloid leukemia in blast crisis, juvenile myelomonocytic leukemia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow failure syndromes are not eligible
* Uncontrolled systemic fungal, bacterial, or viral infection or significant concurrent disease that would compromise patient safety or compliance, study participation, follow up, or interpretation of study results
* Prior exposure to any dose of anthracycline or anthracenedione
* Patients may not receive strong or moderate CYP3A inducers, such as rifampin, within 3 days of enrollment
* Patients may not receive moderate or strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole) within 3 days of enrollment. DRUG: Venetoclax, DRUG: Azacitidine, DRUG: Cytarabine, DRUG: Gemtuzumab Ozogamicin, DRUG: Daunorubicin Hydrochloride, DRUG: Fludarabine Phosphate, DRUG: Idarubicin Hydrochloride, DRUG: Mitoxantrone Hydrochloride, DRUG: Etoposide, DRUG: Gilteritinib
Acute Myeloid Leukemia
Starlight Cardiovascular Lifeline Ductus Arteriosus Stent IDE Study
Amy Pajk - amy.pajk@cchmc.org
ALL
1 minute to 6 months old
NA
NCT07114718
Inclusion Criteria:
• Parental or legal authorized representative provide consent for study enrollment
• Infants \< 6 months of age
• Diagnosis of congenital heart defect with ductal-dependent pulmonary circulation requiring infusion of prostaglandins
• Requires ductus arteriosus stent diameters of 3.5mm or 4mm and stent lengths between 16mm and 28mm
Exclusion Criteria:
• Active blood stream infection
• Active or history of endocarditis
• Body weight \<2.5kg
• Gestational age \<32 weeks at birth
• Complete heart block
• Total Anomalous Pulmonary Venous Return
• Anatomic variation judged to be inappropriate for ductal stenting per the treating interventionalist
• Presence of an aortopulmonary collateral that is expected to require unifocalization
• Non-confluent pulmonary arteries (i.e. isolated pulmonary artery of ductal origin) or bilateral patent ductus arteriosus (PDA)
• Pulmonary atresia with intact ventricular septum with RV-dependent coronary circulation
• Currently participating in an investigational drug study or another device study that would confound the study results
• Patient who is on extracorporeal membrane oxygenation (ECMO), ventricular assist device (VAD), or dialysis prior to ductal stenting procedure
• Major co-morbidities which, in the opinion of the investigator, would negatively alter expected 1-year survival (e.g., intracranial hemorrhage, renal failure, etc.)
• Patient who is undergoing another transcatheter procedure (e.g., atrial septostomy, aortic arch intervention, or right ventricular outflow tract intervention) during or within 24 hours prior to the ductus arteriosus stenting procedure
• Patient who, at the time of enrollment, is deemed not to be a candidate for eventual stage II palliation of single ventricle heart disease, complete surgical repair, nor transcatheter treatment with resultant biventricular circulation
• Patient who does not plan to return to the enrolling center or another participating center for stage II palliation, complete surgical repair, or definitive catheterization procedure
• Contraindications to peri-procedural anticoagulation
• Known to be non-responsive to aspirin or other antiplatelet therapies
• Known hypersensitivity or allergy to Nickel
• Known hypersensitivity to contrast media that cannot be adequately pre-medicated
DEVICE: Ductus Arteriosus Stent
Congenital Heart Disease, Congenital Heart Disease (CHD)
Ductus Arteriosus Stent, pediatric stent, Lifeline Stent
Early Signals of the Transition From Immune Quiescence to Activation in the Liver Allograft Microenvironment and in the Circulation (iSYNAPSE)
Erin Chapman - Erin.Chapman@cchmc.org
ALL
3 years to 13 years old
PHASE2
NCT07549503
Inclusion Criteria:
• Participant and parent or guardian must be able to understand and provide informed assent and consent, respectively
• Recipient of a living or deceased donor Liver transplant (LTx) at \<7 years of age
• \> 3 years but \<7 years after LTx at the time of study enrollment
• Stable liver tests defined as baseline serum alanine aminotransferase (ALT) level \< 30 IU/l and gamma-glutamyl transferase (GGT) level \< 50 IU/l (based on the average of the 3 most recent values prior to screening; all must be within 1 year of screening; 2 must be within 6 months of screening)
• No Acute rejection (AR) or chronic rejection within 12 months of enrollment
• Tacrolimus monotherapy for \> 6 months with baseline 12-hour trough levels \<8 ng/mL (based on the average of 3 values prior to screening; all must be within 1 year of screening; 2 must be within 6 months of screening)
• Participants of childbearing potential must have a negative pregnancy test upon study entry
Exclusion Criteria:
• Liver transplant (LTx) for autoimmune disease, including autoimmune hepatitis or primary sclerosing cholangitis
• LTx for hepatitis B or hepatitis C
• Recipient of any other organ transplant or liver re-transplant, except for patients who have a repeat LTx within 30 days of first LTx who are eligible for enrollment
• \>=50 percent dose increase in tacrolimus within 12 months of enrollment
• Discontinued a second Immunosuppression (IS) agent within 12 months of enrollment
• Systemic illness requiring chronic or recurrent use of IS for which there is a risk of reactivation if tacrolimus is reduced
• Use of medication to treat systemic conditions which in the judgement of the investigator could influence results of the study
• Active or chronic infection requiring treatment
• Inability or unwillingness to comply with the study protocol
• Use of investigational drug within 4 weeks (or 5 half-lives of investigational drug, whichever is longer) of enrollment
• Has any condition that, in the opinion of the investigator, will interfere with safe participation in the trial
DRUG: Immunosuppression Reduction
Liver Transplant
Liver transplant, Immunosuppression
International Collaborative Gaucher Group (ICGG) Gaucher Disease Registry & Pregnancy Sub-registry
Laurie Bailey - laurie.bailey@cchmc.org
ALL
NCT00358943
Inclusion Criteria:
ICGG Gaucher Registry
* All patients with a confirmed diagnosis of Gaucher disease are eligible for inclusion in the Registry. Confirmed diagnosis is defined as a documented β-glucocerebrosidase deficiency and/or mutation in the β-glucocerebrosidase gene.
* For all patients, appropriate patient authorization will be obtained.
Gaucher Pregnancy Sub-registry:
* be enrolled in the ICGG Gaucher Registry.
* be pregnant, or have been pregnant with appropriate medical documentation available.
* provide a signed informed consent and authorization form(s) to participate in the Sub-Registry prior to any Sub-Registry-related data collection being performed.
Exclusion Criteria:
\- No exclusion criteria for participation in the ICGG Gaucher Registry and Sub-registry. Gaucher Disease, Cerebroside Lipidosis Syndrome, Glucocerebrosidase Deficiency Disease, Glucosylceramide Beta-Glucosidase Deficiency Disease
Gaucher Disease, Glucocerebrosidase Deficiency Disease
Improving Outcomes in Pediatric Obstructive Sleep Apnea With Computational Fluid Dynamics (OSA-MRI)
Alex Sierra, MS - alex.sierra@cchmc.org
ALL
3 years to 18 years old
PHASE4
NCT04991389
Inclusion Criteria:
* Male or Female
* Subjects between the ages of 5 to 18 only for Aim 1 and xenon use
* Subjects 3-18 years of age for Aims 2 and 3
* Subjects with persistent moderate or severe OSA after adenotonsillectomy. - -- Persistent moderate or severe OSA will be defined as an oAHI \> 5 per hour of sleep.
* Clinical indication or suspicion of upper-airway obstruction. Examples include but not limited to hypertrophy of the lingual tonsils, disproportionately large tongue, or micrognathia.
* Subjects who have failed a trial of CPAP.
* Subjects whose parents elect to pursue surgery without a trial of CPAP.
* Subjects who require a surgical procedure for OSA based on the clinical assessment of the surgeon (otolaryngologist or plastic surgeon).
Exclusion Criteria:
* Children adequately treated with CPAP.
* Children with braces/metal rods.
* Children who have a contraindication to sedative.
* Standard MRI exclusion criteria as set forth by the CCHMC Department of Radiology. DRUG: 129-Xe
Obstructive Sleep Apnea
OSA, 129Xe, MRI, CFD simulations
Integrative Training Program for Pediatric Sickle Cell Pain (I-STRONG SCD)
Katie Beasley - katie.beasley@cchmc.org
ALL
12 years to 18 years old
NA
NCT06691867
Inclusion Criteria:
* Provision of signed and dated informed consent form for adolescents 18 years old and caregivers' participation
* For children \<18, informed assent and parental informed consent to participate in the study
* Willingness to comply with all study procedures and lifestyle considerations and availability for the duration of the study
* Males and females; Ages 12-18 years for adolescents; no age limitations for caregivers
* Documented diagnosis of sickle cell disease (any genotype) for adolescents
* Adolescent scores at least 3 on the Pediatric Pain Screening Tool
* Adolescent reports typical pain intensity in the past week at least 4 on a 0-10 cm Visual Analog Scale
* Adolescent on stable disease-modifying treatments, if applicable (e.g., hydroxyurea, glutamine, voxelotor, crizanlizumab) as defined by not newly initiated or significantly increased dosages (mg/kg) in the past 3 months
* Speak and read English
Exclusion Criteria:
* An adolescent has comorbid medical conditions typically associated with pain but unrelated to SCD (e.g., rheumatologic disorders or inflammatory bowel disease)
* Adolescent has undergone genetic or hematopoietic stem cell therapy
* Presence of a condition(s) or diagnosis, either physical or psychological, or physical exam finding that precludes participation
* Adolescents receiving active treatment (e.g., weekly appointments with a provider) for nonpharmacological therapies (e.g., structured behavioral pain management, physical therapy, or acupuncture program) that overlap with the active phase of the study intervention BEHAVIORAL: I-STRONG, OTHER: Enhanced Usual Care (EUC)
Sickle Cell Disease
Sickle Cell Pain, Lifestyle considerations, Pediatrics, Behavioral intervention, Mind-body intervention
Evaluation of the SMART IBD App in Pediatric IBD
Jessica King - jessica.king1@cchmc.org
ALL
13 years to 17 years old
NA
NCT07195123
Inclusion Criteria:
* Confirmed diagnosis of IBD (Crohn's Disease, ulcerative colitis, or indeterminate colitis)
* Prescribed at least one daily or weekly medication for treatment of IBD
* \<86% adherence to prescribed medication
* Access to internet via Wi-Fi or data plan and access to smartphone
* 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-IBD
Inflammatory Bowel Disease (IBD), IBD (Inflammatory Bowel Disease), IBD - Inflammatory Bowel Disease, Ulcerative Colitis (UC), Indeterminate Colitis, Crohn Disease (CD), IBD
IBD, Inflammatory Bowel Disease, Ulcerative Colitis, Indeterminate Colitis, Crohns Disease
Biomarker Validation in Motor System Physiology in Attention Deficit Hyperactivity Disorder (AMPAIII)
Karlee Migneault - karlee.migneault@cchmc.org
AMPAIII
ALL
8 years to 12 years old
PHASE4
NCT04421248
Inclusion Criteria:
* Either gender, any race, ethnicity or socioeconomic status
* Currently between 8 years 0 months and 12 years, 11 months, 30 days
* Willing to answer questions about ADHD and related diagnoses
* For children with ADHD prescribed stimulant medications, willing to suspend taking medications as specified in the study procedures
* For children with ADHD, willing to participate in the single dose, randomized crossover study to probe acute effects of methylphenidate on biomarkers
* Right hand dominant (predominately right-handed)
* Able to participate in and sign an informed consent
* ADHD inclusion: The diagnosis of ADHD will be based on Diagnostic and Statistical Manual version 5 (DSM-5) criteria using standard rating scales and a structured diagnostic interview. Oppositional Defiant Disorder is permitted; Conduct disorder is excluded.
* Typically Developing (healthy control) inclusion: Free of ADHD or other developmental or psychiatric disorders based on DSM-5 criteria using standard rating scales and a structured diagnostic interview.
Exclusion Criteria:
* Known diagnosis of mental retardation, cerebral palsy, Autism Spectrum Disorder, traumatic brain injury, brain tumor, epilepsy, or other serious neurological disorder.
* Major Depression, Bipolar Disorder, Conduct Disorder, Adjustment Disorder, other Anxiety Disorders, or other developmental psychiatric diagnoses.
* For females, onset of menses, pregnancy.
* Current use of antidepressants, non-stimulant ADHD medications, dopamine blocking agents, mood stabilizers.
* Implanted brain stimulator, vagal nerve stimulator, ventriculo-peritoneal shunt, cardiac pacemaker, or implanted medication port.
* Diagnosis of a speech/language disorder or a Reading Disability (RD). DRUG: Methylphenidate, DRUG: Placebo
Attention Deficit Hyperactivity Disorder Combined
Treating Young Children With Attention Deficit Hyperactivity Disorder (TYCA)
Hannah Bush, MA - ddbp.adhd.research@cchmc.org
TYCA
ALL
3 years to 5 years old
PHASE4
NCT07300956
Inclusion Criteria:
• Males or females 3 to 5 years of age, inclusive (e.g. children age 5 years, 11 months are eligible).
• Child has a confirmed diagnosis of moderate or severe Attention-Deficit/Hyperactivity Disorder (diagnostic code: F90.9) based on Diagnostic and Statistical Manual of Mental Disorders - 5th Edition (DSM-5) criteria, review of supportive evidence (caregiver interview, behavioral observations, Vanderbilt Attention-Deficit/Hyperactivity Disorder Rating Scale results, any school or daycare information provided by caregiver).
• Clinician-rated Clinical Global Impairment-Severity (see description below) rating of ≥4 (denoting moderate or greater impairment due to their Attention-Deficit/Hyperactivity Disorder symptoms).
• The child's clinician and caretakers have decided on or are considering initiating drug therapy (with either Methylphenidate or Guanfacine).
• Primary language is English or Spanish.
Exclusion Criteria:
• History of taking Methylphenidate or Guanfacine. Prior use of other Attention-Deficit/Hyperactivity Disorder medications or other psychotropic medications is allowed.
• Current use of other Attention-Deficit/Hyperactivity Disorder medications (e.g., amphetamines), other psychotropic medications (e.g., atypical antipsychotics or serotonin reuptake inhibitors), or centrally active depressants (such as phenothiazines, barbiturates, or benzodiazepines)
• Electronic Health Record documentation of moderate to severe global developmental delay (F88) or intellectual disability (F70), or a score of \<55 on the Vineland Adaptive Behavior Scales-3.
• Medical contraindications to taking Methylphenidate or Guanfacine, including cardiac risk factors (e.g. known structural cardiac abnormalities, cardiomyopathy, serious cardiac arrhythmias, coronary artery disease, or other serious cardiac disease), increased intraocular pressure, glaucoma, verbal tics, Tourette's Syndrome, psychosis
DRUG: Guanfacine (GUA), DRUG: Methylphenidate (MPH)
Attention-Deficit/Hyperactivity Disorder (ADHD)
Attention-Deficit/Hyperactivity Disorder, Methylphenidate, Guanfacine, Preschool Children, Comparative Effectiveness, Prospective Study
Testing a Standardized Approach to Surgery and Chemotherapy for Type I Pleuropulmonary Blastoma or the Addition of an Anti-cancer Drug, Topotecan, to the Usual Treatment for Types II and III Pleuropulmonary Blastoma
- cancer@cchmc.org
ALL
Up to 21 years old
PHASE3
NCT06647953
Inclusion Criteria:
* 21 years of age or younger
* Newly diagnosed PPB. Note that patients with known germline DICER1 variant or mosaicism with a large, solid unresectable thoracic mass with imaging features characteristic for Type II or III PPB are eligible without histologic confirmation of the diagnosis if a biopsy of the mass is not considered safe or feasible
* Individuals are eligible based on institutional diagnosis of Type I, Ir, II or III PPB diagnosed within 60 days prior to enrollment. Children with Type II or III PPB at risk for clinical decompensation may receive protocol therapy while awaiting rapid central pathology review. Children with Type I or Ir PPB will be assigned to chemotherapy vs. observation based on imaging and central pathology review diagnosis. Type I and Ir patients should not begin chemotherapy prior to return of central pathology results
* For patients with Type II or III PPB (within 7 days prior to enrollment): A serum creatinine based on age/sex as follows:
* Age: 1 month to \< 6 months - Maximum Serum Creatinine (mg/dL): 0.4 (Male), 0.4 (Female)
* Age: 6 months to \< 1 year - Maximum Serum Creatinine (mg/dL): 0.5 (Male), 0.5 (Female)
* Age: 1 to \< 2 years - Maximum Serum Creatinine (mg/dL): 0.6 (Male), 0.6 (Female)
* Age: 2 to \< 6 years - Maximum Serum Creatinine (mg/dL): 0.8 (Male), 0.8 (Female)
* Age: 6 to \< 10 years - Maximum Serum Creatinine (mg/dL): 1 (Male), 1 (Female)
* Age: 10 to \< 13 years - Maximum Serum Creatinine (mg/dL): 1.2 (Male), 1.2 (Female)
* Age: 13 to \< 16 years - Maximum Serum Creatinine (mg/dL): 1.5 (Male), 1.4 (Female)
* Age: ≥ 16 years - Maximum Serum Creatinine (mg/dL): 1.7 (Male), 1.4 (Female) OR - A 24 hour urine creatinine clearance ≥ 60 mL/min/1.73 m\^2 OR - A glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
* Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
* For patients with Type II or III PPB (within 7 days prior to enrollment): Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age
* For patients with Type II or III PPB (within 7 days prior to enrollment): Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase \[ALT\]) ≤ 135 U/L
* 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 (within 21 days prior to start of protocol therapy)
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible as long as they are NOT receiving anti-retroviral agents that are strong inhibitors or inducers of CYP3A4
Exclusion Criteria:
* Administration of prior PPB-directed chemotherapy is an exclusion criterion. Prior treatment for another malignancy is not an exclusion criterion
* Patients with known Charcot-Marie-Tooth disease
* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential
* Lactating females who plan to breastfeed their infants
* Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation
* 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 PROCEDURE: Biospecimen Collection, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Scan, PROCEDURE: Computed Tomography, DRUG: Cyclophosphamide, BIOLOGICAL: Dactinomycin, DRUG: Dexrazoxane, DRUG: Doxorubicin, PROCEDURE: Echocardiography Test, DRUG: Ifosfamide, PROCEDURE: Magnetic Resonance Imaging, PROCEDURE: Multigated Acquisition Scan, OTHER: Patient Observation, PROCEDURE: Positron Emission Tomography, DRUG: Topotecan, PROCEDURE: Ultrasound Imaging, DRUG: Vincristine
Pleuropulmonary Blastoma
Regional Monitoring of CF Lung Disease
Carrie Stevens, BS - carrie.stevens@cchmc.org
ALL
12 years to 21 years old
EARLY_PHASE1
NCT06339593
Inclusion Criteria:
* 1 Written informed consent (and assent when applicable) obtained from subject or subject's legal representative.
2 Use of highly effective modulators for more than 30 days (ie. Trikafta) 3 Willingness and ability to adhere to the study visit schedule and other protocol requirements.
4 Documentation of a CF diagnosis with prescription of Mechanical ACT 5 Ages 12-21 inclusive, at the time of consent. 6 Clinically stable with no respiratory tract infection or recent exacerbations. 7 Treating CF physician agreeable to study procedures. Only applicable to Aim 3.
8 No change in chronic maintenance therapies in the 28 days prior to enrollment.
9 Ability to cooperate with MRI procedures.
Exclusion Criteria:
• Standard MRI exclusions (metal implants, claustrophobia).
• For females of childbearing potential: Positive urine pregnancy test or Lactating.
• Acute respiratory symptoms (e.g., wheezing) at the time of the MRI
• Chronic lung or liver or pancreatic disease not related to CF.
• Any other condition that, in the opinion of the Investigator, would preclude informed consent or assent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives.
PROCEDURE: Airway-clearance vest, DRUG: Hyperpolarized Xe129
Cystic Fibrosis
Survivors Journey+ (SJ)
Zyah Flagg - zyah.flagg@cchmc.org
ALL
15 years to 25 years old
NA
NCT07321353
Inclusion Criteria:
* a diagnosis of a pediatric intracranial tumor
* tumor-directed treatment completed \> 12 months ago (treatment included: surgery, radiation, or chemotherapy)
* lives with parent/guardian(s)
* language: English must be the primary spoken language in the home
Exclusion Criteria:
* history of tuberous sclerosis or neurofibromatosis
* treatment \< 12 months ago and/or treatment did not include surgery, radiation, or chemotherapy
* history of psychiatric hospitalization
* resides outside of the family home
* history of autism, reactive attachment disorder, psychosis, or other psychiatric diagnoses/conditions associated with significant risk of harm to self or others per caregiver
* English is not the primary language spoken in the home BEHAVIORAL: Survivor's Journey+
Pediatric Brain Tumor
pediatric brain tumor survivors, online learning, Adolescent young adult, Family, Digital, Problem Solving
Ferric Citrate and Chronic Kidney Disease in Children (FIT4KID)
Elizabeth Siry - elizabeth.siry@cchmc.org
ALL
6 years to 18 years old
PHASE2
NCT04741646
Inclusion Criteria:
• Ages 6 to 18 years (inclusive);
• Estimated Glomerular Filtration Rate (GFR) of 15-59 ml/min per 1.73 m2 by modified Chronic Kidney disease in Children (CKiD) under 25 (U25) formula;56
• Serum phosphate \<=5.9 mg/dl;
• Serum ferritin \<500 ng/ml and TSAT \<50%;
• For those patients treated with growth hormone, calcitriol, nutritional vitamin D, iron, and/or erythropoiesis-stimulating agents (ESAs) such treatments must have stable dosing for at least 2 weeks prior to screening;
• Able to swallow tablets;
• Able to eat at least two meals a day;
• In the opinion of the investigator, willing and able to follow the study treatment regimen and comply with the site investigator's recommendations.
Exclusion Criteria:
• Patients currently treated with phosphate binders.
• History of allergy to all ingredients (including non-medical ingredients) in both products (i.e. investigational product and placebo)
• Current intestinal malabsorption, documented in the medical record; disease, inflammatory bowel syndrome, and/or Crohn's Disease.
• Anticipated initiation of dialysis or kidney transplantation within 6 months
• Current or planned future systemic immunosuppressive therapy
• Prior solid organ transplantation
• Receipt of bone marrow transplant within two years of screening
• Current pregnancy, lactation or female subjects who have reached menarche, unless using highly-effective contraception as outlined in section 7.1.1 of Protocol
• Patients participating in other interventional study (observational study participation permitted)
• Poor adherence to medical treatments in the opinion of the investigator
• Cystinosis
• Fanconi syndrome
• Hemochromatosis or laboratory tests indicating possible hemochromatosis or other iron overload (primary or secondary) syndrome
DRUG: Ferric Citrate, DRUG: Placebo
Chronic Kidney Diseases
Pediatric, CKD, Phosphate Binder
Safety Study of Unlicensed IND Cord Blood Units Manufactured by the National Cord Blood Program for Unrelated Transplantation
Stephanie Edwards - stephanieL.edwards@cchmc.org
ALL
PHASE2
NCT01656603
Inclusion Criteria:
• Diagnosis: Patients with disorders affecting the hematopoietic system that are inherited, acquired, or result from myeloablative treatment.
• Patients: Patients of any age and either gender
• Cord blood product manufactured by the NCBP (at least one, if the graft contains more than one units)
Exclusion Criteria:
• Patients who are receiving licensed cord blood products (only)
• Patients who are receiving unlicensed cord blood products from other banks (only)
• Patients who are transplanted at non-US transplant centers
• Patients who are receiving cord blood products that will be "manipulated" post-thaw (e.g., ex vivo expansion, incubation in vitro, etc.)
BIOLOGICAL: unlicensed CBU
Infusion Reactions
cord blood, transplantation, stem cells, adverse event
CLN-049 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)
- cancer@cchmc.org
ALL
18 years and over
PHASE1
NCT05143996
Inclusion Criteria:
• Aged ≥ 18 years of age.
• Patient has a confirmed diagnosis of recurrent or refractory AML or MDS: Parts A, B, C: i. AML either de novo or secondary ii. MDS with at least 5% blasts that is relapsed after or refractory to hypomethylating agent (HMA) therapy iii. Patient has received, and has progressed, recurred, or is intolerant of approved therapeutic options that are available or declines treatment with these therapies Part D: i. Confirmed diagnosis of de novo or secondary R/R AML (includes patients with MDS/AML) ii. Patient has received no more than 2 prior lines of therapy iii. Patients must have exhausted, be ineligible for, be intolerant of, or otherwise not be considered appropriate candidates for available therapies considered suitable for the individual patient (including targeted therapies) iv. Patients must have a recent assessment of TP53 mutation status by an approved local laboratory. Part E: i. Patient has a confirmed diagnosis of de novo or secondary newly diagnosed AML (includes patients with MDS/AML) with no prior lines of AML-directed therapy ii. Patient must have evidence of a positive recent assessment of TP53 mutation status
• White blood cell (WBC) count at the time of the first dose is \< 20,000/uL
• Eastern Cooperative Oncology Group (ECOG) performance status is 0 to 2.
• Toxicities related to prior study therapy should have resolved to Grade 1 or less according to criteria of NCI CTCAE v5.0
• The patient's laboratory values meet the following criteria:
• Creatinine clearance (CrCl) as calculated by the Cockcroft-Gault formula must be ≥ 45 mL/min;
• Total bilirubin ≤ 1.5 × ULN.
• AST and ALT ≤ 3.0 × ULN (unless attributed to leukemic involvement).
Exclusion Criteria:
• Diagnosis of acute promyelocytic leukemia (APL)
• Active central nervous system (CNS) leukemia.
• Isolated extramedullary relapse
• Prior organ allograft
• Prior history of allogeneic hematopoietic transplantation:
• In Parts A, B, and C: Prior history of allogeneic hematopoietic transplantation within six months of treatment or with clinical or laboratory evidence of GVHD, or requiring ongoing treatment with immune suppression
• In Parts D and E: Prior history of allogeneic hematopoietic transplantation within twelve months of treatment or with clinical or laboratory evidence of GVHD, or requiring ongoing treatment with immune suppression
• Treatment with any of the following:
• Radiation therapy (XRT) within 28 days of the first dose of CLN-049, or craniospinal XRT within 8 weeks of the first dose of CLN-049, or history of total body irradiation (TBI).
• Prior immunotherapy with checkpoint inhibitors ≤ 42 days prior to the first dose of CLN-049.
• Prior history of chimeric antigen receptor (CAR-T) cell therapy or other modified T cell therapy.
• Anti-leukemic therapy except hydroxyurea for cytoreduction, and intrathecal chemotherapy ≤ 14 days or 5 half-lives, whichever is shorter, prior to the first dose of CLN-049.
• Short-acting hematopoietic growth factors ≤ 7 days prior to the first dose of CLN-049
• Long-acting growth factors ≤ 14 days prior to the first dose of CLN-049.
• Systemic glucocorticoid therapy (except equivalent of \< 10 mg prednisone daily) or other immune-suppressive drugs ≤ 14 days prior to the first dose of CLN-049
• Prior treatment with a FLT3-directed bispecific molecule, or a FLT3-targeted antibody.
• Currently participating/previously participated in an interventional study and received an investigational drug within 14 days (or five half-lives, whichever is longer) prior to the first dose of CLN-049.
• Patients with concomitant second malignancies requiring active treatment in the past 12 months, or if additional therapy is required or anticipated during study participation.
• Patients with any active autoimmune disease or a history of known or suspected autoimmune disease, or history of a syndrome that requires systemic corticosteroids or immunosuppressive medications
• A serious uncontrolled medical disorder that would impair the ability of the patient to receive protocol therapy or whose control may be jeopardized by the complications of this therapy.
• Any concurrent condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might compromise patient safety or interfere with the evaluation of the safety of the drug.
• Active uncontrolled infection within seven days of first dose of CLN-049.
• Has a history of, or a positive test for Human Immunodeficiency Virus (HIV) 1/2 or primary immunodeficiency disease such as HIV.
• Known history of hepatitis B (with positive testing for either hepatitis B surface antigen \[HBsAg\] or hepatitis B core Ab), hepatitis C (HCV) infection (with positive testing for HCV antibody and/or HCV ribonucleic acid \[RNA\] in serum), or acute hepatitis A (with positive testing for hepatitis A IgM).
• Active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection
• History of the following events in conjunction with prior treatment with immunotherapy: Grade 3 or greater neurotoxicity, ocular toxicity, pneumonitis, myocarditis, or colitis; liver dysfunction meeting the laboratory criteria for Hy's Law.
• Live virus vaccines within 28 days of the first dose of CLN-049, during treatment, and until the end of last dose of CLN-049.
• QT interval corrected for heart rate using Fridericia's formula (QTcF) of ≥ 480 milliseconds.
• Patient has history of drug-related anaphylactic reactions to any components of CLN-049. History of Grade 4 anaphylactic reaction to any bispecific molecule or monoclonal antibody therapy.
• Known history of prior human anti-human antibody response. Patients will not be screened for human anti-human antibody prior to study participation.
DRUG: CLN-049
Relapsed/Refractory Acute Myeloid Leukemia (AML), Myelodysplastic Syndrome (MDS), TP53-mutated MDS and AML
Phase III DAS181 Lower Tract PIV Infection in Immunocompromised Subjects (Substudy: DAS181 for COVID-19): RCT Study
Caitlin Brammer - caitlin.brammer@cchmc.org
ALL
PHASE3
NCT03808922
Inclusion Criteria:
• At the time of randomization, requires supplemental oxygen ≥2 LPM due to hypoxemia.
• Immunocompromised, as defined by one or more of the following: * Received an autologous or allogeneic hematopoietic stem cell transplantation (HSCT) at any time in the past * Received a solid organ transplant at any time in the past * Has been or is currently being treated with chemotherapy for hematologic malignancies (e.g., leukemia, myeloma, lymphoma) and/or solid tumor malignancies (e.g., lung, breast, brain cancer) at any time in the past * Has an immunodeficiency due to congenital abnormality (only applicable to subjects age \< 18 years old) or pre-term birth (only applicable to subjects age ≤ 2 years old)
• Has, within 3 days prior to randomization, a confirmed LRTI with a sialic acid dependent respiratory virus
• If female, subject must meet one of the following conditions: * Not be of childbearing potential or * Be of childbearing potential and have a negative urine/serum pregnancy test and agrees to practice an acceptable method of contraception
• Non-vasectomized males are required to practice effective birth control methods
• Capable of understanding and complying with procedures as outlined in the protocol
• Provides signed informed consent prior to the initiation of any screening or study-specific procedures For COVID-19 sub study:
• Be ≥18 years of age
• Provide adequate medical history to permit accurate stratification (but health status may be healthy, high-risk conditions, or immunocompromised).
• Prior to SARS CoV 2 infection, has the ability to carry out self-care activities of daily living (basic ADL)
• Have lower respiratory tract infection (LRTI) confirmed by CT imaging, with or without contrast, to involve at least 2 lobes of the lung.
• Has laboratory-confirmation of the presence of SARS CoV 2 in the respiratory tract by at least one of the following samples
• Satisfy inclusion criteria #1, 4, 5, 6, 7 of the main study
Exclusion Criteria:
• Subjects may not be on hospice care or, in the opinion of the investigator, have a low chance of survival during the first 10 days of treatment
• Subjects with Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), or Alkaline Phosphatase (ALP) ≥3x ULN and Total Bilirubin (TBILI) ≥2x ULN Note: Subjects with ALT/AST/ALP ≥ 3x ULN AND TB ≥2x ULN that have been chronically stable (for \>1 year on more than one assessments) due to known liver pathology including malignancy (primary or metastasis), chronic medications, transplantation, or chronic infection will not be excluded
• Female subjects breastfeeding or planning to breastfeed at any time through 30 days after the last dose of study drug
• Subjects taking any other investigational drug used to treat pulmonary infection.
• Psychiatric or cognitive illness or recreational drug/alcohol use that, in the opinion of the principal investigator, would affect subject safety and/or compliance
• Subjects with known hypersensitivity to DAS181 and/or any of its components
• Subjects with severe sepsis due to either their baseline SAD-RV infection or a concurrent viral, bacterial, or fungal infection and meet at least one of the following criteria: * Has evidence of vital organ failure outside of the lung (e.g., liver, kidney) * Requires vasopressors to maintain blood pressure For COVID-19 sub study:
• Subjects requiring invasive mechanical, Bi-PAP or CPAP ventilation at randomization.
• Subjects receiving any other investigational or empiric treatment for SARS-2-CoV (either as part of a clinical trial or under emergency approval (approved agents for the management of symptoms, e.g., fever, are permitted).
• Subjects who are known HIV-positive (and not undetectable at most recent HIV RNA assessment)
• Subjects who are currently taking immunomodulating biologics (e.g, interferons, interleukin)
• Subjects with severe sepsis due to either their SARS-CoV-2 infection or a concurrent viral, bacterial, or fungal infection and meeting at least one of the following criteria: * Have evidence of vital organ failure outside of the lung (e.g., liver, kidney) * Require vasopressors to maintain blood pressure
• Subjects meeting exclusion criteria #2, 3, 5 and 6 of the main study
DRUG: DAS181, DRUG: Placebo, DRUG: DAS181 COVID-19, DRUG: DAS181 OL
Lower Respiratory Tract Infection, Parainfluenza, Immunocompromised, COVID-19
Parainfluenza, PIV, Immunocompromised, Lower Respiratory Tract Infection, LRTI, COVID19, SARS-CoV-2, Coronavirus, Ansun
Abatacept for the Treatment of Common Variable Immunodeficiency With Interstitial Lung Disease (ABCVILD)
Michael Jordan - Michael.Jordan@cchmc.org
ALL
4 years and over
PHASE2
NCT04925375
Inclusion Criteria:
• Diagnosis of CVID according to the international consensus document (ICON)
• Age 4 years or above
• Serum IgG at least 2 standard deviations below the age adjusted normal
• Decreased serum IgA and/or serum IgM
• Abnormal specific antibody response to immunization
• Exclusion of secondary immunodeficiency
• On replacement immunoglobulin for at least 6 months and willing to maintain throughout study
• Granulomatous-lymphocytic interstitial lung disease with a lymphocytic component diagnosed by lung biopsy prior to study entry, wedge biopsy preferred.
• Persistence or worsening of interstitial lung disease measured on serial CT imaging of the lung at least 6 months apart, with the latest assessment within 3 months of study entry.
• Signed written informed consent
• Willing to allow storage of biological specimens for future use in medical research.
• Female subjects of childbearing potential must agree to an effective form of birth control such as hormone based contraceptive, intrauterine device, condoms/barrier, surgically sterile partner, or abstinence.
• Fertile, non-vasectomized males with a female partner of childbearing potential should use condoms throughout the study and for 3 months after the last dose
Exclusion Criteria:
• History of hypersensitivity to abatacept or any of its components
• Has received any lymphocyte depleting agents including anti-CD20 monoclonal antibodies, alemtuzumab, ATG in the preceding 6 months
• Has received abatacept, cyclophosphamide, tumor necrosis factor inhibitors, or pulse steroids (defined as \>15mg/kg/day of methylprednisone or corticosteroid equivalent) within the past 3 months
• Have started or increased any of the following immune modulating drugs within 3 months of enrolling and 3 months from initial CT chest: azathioprine, cyclosporine, tacrolimus, mercaptopurine, methotrexate, mycophenolate mofetil, or sirolimus
• History of HIV infection (positive PCR)
• Chronic untreated hepatitis B or C (positive PCR)
• Active tuberculosis (TB) by positive QuantiFERON gold. If history of latent TB, then must supply evidence of completing treatment.
• Persistent Epstein-Barr Virus (EBV) load ≥ 1,000 units/mL blood checked twice at least 1 month apart
• Other uncontrolled infections
• Live vaccine given within 6 weeks of the start of the trial
• Malignancy or treated for malignancy within the past year
• Currently pregnant or breast feeding
• Life expectancy less than 1 month
• Subjects unwilling to self-administer or have a parent/caregiver self-administer subcutaneous injections at home
• Other conditions that the investigators feel contraindicate participation in the study Inclusion criteria for Extended Treatment Plan: * Patients must have completed the abatacept for the treatment of Interstitial Lung Disease in Common Variable Immunodeficiency (ABCVILD) trial * Patients must have demonstrated positive response to abatacept. * Patients must provide informed consent to participate in the Extended Treatment Plan. Exclusion criteria for Extended Treatment Plan: • Patients who experienced SAEs during the original trial, and such SAEs were determined as related to treatment, or patients who in the opinion of the investigator would not benefit from the extended treatment option.
DRUG: Abatacept, OTHER: Placebo
Interstitial Lung Disease, Common Variable Immunodeficiency
Lutathera for Treatment of Recurrent or Progressive High-Grade CNS Tumors
- cancer@cchmc.org
ALL
4 years to 39 years old
PHASE1
NCT05278208
All participants must meet the following inclusion and exclusion criteria. No exceptions will be given. Imaging studies to establish eligibility must be done within three weeks prior to enrollment. All other clinical evaluations to establish eligibility (except for \[68Ga\]Ga-DOTATATE PET) must be done within 7 days prior to enrollment.
• Screening Criteria
• 1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic/clinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection. Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.
• 2 Prior Therapy Patients must have recurred/progressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.
• 3 Screening Consent Participant/legal guardian is willing to sign a screening consent for \[68Ga\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.
• Eligibility Criteria * Phase I Age Patient must be ≥ 4 and \<12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible. * Phase II Age Patient must be 12 to \ • Inclusion Criteria
• 1 Uptake on \[68Ga\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET/CT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).
• 2 Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.
• 3 Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.
• 4 Investigational/Biologic Agent ●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment. 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. ●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.
• 5 Radiation Patients must have had their last fraction of: * Craniospinal irradiation or total body irradiation or radiation to \> 50% of pelvis \> 3 months prior to enrollment. * Focal irradiation \> 4 weeks prior to enrollment
• 6 Stem Cell Transplant Patient must be: * ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease * ≥ 3 months since autologous stem cell transplant prior to enrollment
• 7 Growth Factors Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g. filgrastim, sargramostim or erythropoietin). Two weeks must have elapsed if patients received long-acting formulations.
• 8 Thrombopoietin receptor agonist * Phase I: Patients must be off thrombopoietin receptor agonists for at least 1 week prior to enrollment (e.g. romiplostim, eltrombopag) * Phase II: Patients can receive concurrent thrombopoietin receptor agonists
• 9 Somatostatin analogs Patients must be off long-acting somatostatin analogs for at least 4 weeks and off short-acting somastatin analogs (i.e., octreotide) for at least 24 hours.
• 10 Neurologic Status * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment, documented by a detailed neurological exam. * Patients with seizure disorders may be enrolled if seizures are well controlled.
• 11 Performance Status Karnofsky Performance Scale (KPS for \> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of enrollment must be ≥ 50. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• 12 Organ Function Patients must have adequate organ and marrow function, for eligibility and enrollment, as defined below: * Adequate Bone Marrow Function as defined as: * Absolute neutrophil count ≥ 1.0 x 109 cells/ L * Platelets ≥100 x 109 cells/ L (unsupported, defined as no platelet transfusion within 7 days) * Hemoglobin ≥8 g/dl (may receive transfusions) * Adequate Renal Function as defined as: * Creatinine clearance or radioisotope GFR \>70mL/min/1.73m2 OR * A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to \< 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females. ≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females. * Adequate Liver Function as defined as: * Total bilirubin ≤ 3 times institutional upper limit of normal (ULN) for age * AST(SGOT)/ALT(SGPT) ≤ 3 times institutional ULN * Serum albumin ≥ 2g/dL * Coagulation parameters: INR \<1.5 times ULN and aPTT \<1.5 times ULN unless patients are receiving therapeutic anticoagulation which affects these parameters * Adequate Cardiac Function as defined as: * Ejection fraction of ≥ 55% by echocardiogram * Serum electrolytes (Sodium, Potassium, Chloride) within institutional limits of normal (patients can be on enteral supplementation)
• 13 Corticosteroids Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment, with a maximum dexamethasone dose of 2.5mg/m2/day.
• 14 Pregnancy Status Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• 15 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 at least 7 months after drug cessation in females of childbearing potential and for at least 4 months after drug cessation in males of child fathering potential.
• 16 Informed Consent The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines.
• Exclusion Criteria
• 1 Confirmed bone marrow metastatic disease Patients with confirmed metastatic disease to bone marrow are ineligible.
• 2 Presence of bulky disease Patients with bulky disease on imaging as described below are ineligible. Treating physicians are encouraged to request a rapid central imaging review to confirm fulfillment of these criteria if there are questions or concerns. Bulky disease is defined as: * Tumor with evidence of clinically significant uncal herniation or midline shift. * Tumor with diameter of \>5cm in one dimension on T2/FLAIR. * Tumor that in the opinion of the site investigator shows significant mass effect in either the brain or spine. Note that patients with metastatic or multi-focal disease (with exception of bone marrow) are eligible as long as no sites of disease meet above criteria for bulky disease.
• 3 Breast-feeding Nursing mothers are excluded from this study. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Lutathera.
• 4 Concurrent Illness * Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient's prior malignancy has been in remission for at least 5 years from the end of treatment. * Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results. * Patients with type I diabetes.
• 5 Concomitant Medications * Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible. * Prior or current treatment with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC.
• 6 Prisoners will be excluded from this study.
• 7 Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits, obtain follow-up studies required to assess toxicity to therapy, or adhere to drug administration plan, other study procedures, and study restrictions.
• Inclusion of Women and Minorities Both males and females of all races and ethnic groups are eligible for this study.
• Screening Criteria
• 1 Diagnosis Patient must have a diagnosis of primary high-grade CNS tumor (any histopathologic diagnosis that is WHO grade III-IV) or meningioma (any histologic grade) that is recurrent, progressive, or refractory. Note that patients with DIPG (based on radiographic/clinical diagnosis) who have undergone biopsy will be eligible with histologic diagnosis of grade II-IV infiltrating glioma. All tumors must have histologic verification either at the time of diagnosis or recurrence, except for patients meningioma who have not previously undergone biopsy or resection. Note: Refractory disease is defined as the presence of persistent abnormality on conventional MRI that is further distinguished by histology (biopsy or sample of lesion) or advanced imaging, OR as determined by the treating physician and discussed with the primary investigator prior to enrollment.
• 2 Prior Therapy Patients must have recurred/progressed following prior standard therapy for their tumor. Note: Patients with meningioma, atypical meningioma, or anaplastic meningioma must have received at least surgical resection or radiation.
• 3 Screening Consent Participant/legal guardian is willing to sign a screening consent for \[68Ga\]Ga-DOTATATE PET imaging. The screening consent is to be obtained according to institutional guidelines. Assent, when appropriate, will be obtained according to institutional guidelines.
• Eligibility Criteria * Phase I Age Patient must be ≥ 4 and \<12 years of age at the time of enrollment. Disease Status: Patients who participate in the efficacy expansion cohort must have bi-dimensionally measurable disease, defined as at least one lesion that can be accurately measured in at least two dimensions Patients with measurable extraneural disease only are also eligible. * Phase II Age Patient must be 12 to \ • Inclusion Criteria
• 1 Uptake on \[68Ga\]Ga-DOTATATE PET Patients must have uptake on DOTATATE PET/CT in at least one tumor lesion (corresponding to known disease) equivalent to a Krenning score ≥2 (confirmed by central radiology review).
• 2 Prior Therapy Patients must have recovered from the acute treatment related toxicities (defined as ≤ grade 1 if not defined in eligibility criteria) of all prior chemotherapy, immunotherapy, radiotherapy, or any other treatment modality prior to entering this study.
• 3 Chemotherapy Patients must have received their last dose of known myelosuppressive anticancer therapy at least 21 days prior to enrollment or at least 42 days if nitrosourea.
• 4 Investigational/Biologic Agent ●Biologic or investigational agent (anti-neoplastic): Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the investigational or biologic agent ≥ 7 days prior to study enrollment. 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. ●Monoclonal Antibodies and agents with known prolonged half-lives: Patient must have recovered from any acute toxicity potentially related to the agent and received their last dose of the agent ≥ 28 days prior to study enrollment.
• 5 Radiation Patients must have had their last fraction of: * Craniospinal irradiation or total body irradiation or radiation to \> 50% of pelvis \> 3 months prior to enrollment. * Focal irradiation \> 4 weeks prior to enrollment
• 6 Stem Cell Transplant Patient must be: * ≥ 6 months since allogeneic stem cell transplant prior to enrollment with no evidence of active graft vs. host disease * ≥ 3 months since autologous stem cell transplant prior to enrollment
• 7 Growth Factors Patients must be off all colony-forming growth factor(s) for at least 1 week prior to enrollment (e.g. filgrastim, sargramostim or erythropoietin). Two weeks must have elapsed if patients received long-acting formulations.
• 8 Thrombopoietin receptor agonist * Phase I: Patients must be off thrombopoietin receptor agonists for at least 1 week prior to enrollment (e.g. romiplostim, eltrombopag) * Phase II: Patients can receive concurrent thrombopoietin receptor agonists
• 9 Somatostatin analogs Patients must be off long-acting somatostatin analogs for at least 4 weeks and off short-acting somastatin analogs (i.e., octreotide) for at least 24 hours.
• 10 Neurologic Status * Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to enrollment, documented by a detailed neurological exam. * Patients with seizure disorders may be enrolled if seizures are well controlled.
• 11 Performance Status Karnofsky Performance Scale (KPS for \> 16 years of age) or Lansky Performance Score (LPS for ≤ 16 years of age) assessed within two weeks of enrollment must be ≥ 50. Patients who are unable to walk because of neurologic deficits, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
• 12 Organ Function Patients must have adequate organ and marrow function, for eligibility and enrollment, as defined below: * Adequate Bone Marrow Function as defined as: * Absolute neutrophil count ≥ 1.0 x 109 cells/ L * Platelets ≥100 x 109 cells/ L (unsupported, defined as no platelet transfusion within 7 days) * Hemoglobin ≥8 g/dl (may receive transfusions) * Adequate Renal Function as defined as: * Creatinine clearance or radioisotope GFR \>70mL/min/1.73m2 OR * A serum creatinine based on (Schwartz et al. J. Peds, 106:522, 1985) age/gender as follows: 1 to \< 2 years: maximum serum creatinine 0.6 mg/dL for males and females. 2 to \< 6 years: maximum serum creatinine 0.8 mg/dL for males and females. 6 to \< 10 years: maximum serum creatinine 1.0 mg/dL for males and females. 10 to \< 13 years: maximum serum creatinine 1.2 mg/dL for males and females. 13 to \< 16 years: maximum serum creatinine 1.5 mg/dL for males and 1.4 mg/dL for females. ≥ 16 years: maximum serum creatinine 1.7 mg/dL for males and 1.4 mg/dL for females. * Adequate Liver Function as defined as: * Total bilirubin ≤ 3 times institutional upper limit of normal (ULN) for age * AST(SGOT)/ALT(SGPT) ≤ 3 times institutional ULN * Serum albumin ≥ 2g/dL * Coagulation parameters: INR \<1.5 times ULN and aPTT \<1.5 times ULN unless patients are receiving therapeutic anticoagulation which affects these parameters * Adequate Cardiac Function as defined as: * Ejection fraction of ≥ 55% by echocardiogram * Serum electrolytes (Sodium, Potassium, Chloride) within institutional limits of normal (patients can be on enteral supplementation)
• 13 Corticosteroids Patients who are receiving dexamethasone must be on a stable or decreasing dose for at least 1 week prior to enrollment, with a maximum dexamethasone dose of 2.5mg/m2/day.
• 14 Pregnancy Status Female patients of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• 15 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 at least 7 months after drug cessation in females of childbearing potential and for at least 4 months after drug cessation in males of child fathering potential.
• 16 Informed Consent The patient or parent/guardian is able to understand the consent and is willing to sign a written informed consent document according to institutional guidelines.
• Exclusion Criteria
• 1 Confirmed bone marrow metastatic disease Patients with confirmed metastatic disease to bone marrow are ineligible.
• 2 Presence of bulky disease Patients with bulky disease on imaging as described below are ineligible. Treating physicians are encouraged to request a rapid central imaging review to confirm fulfillment of these criteria if there are questions or concerns. Bulky disease is defined as: * Tumor with evidence of clinically significant uncal herniation or midline shift. * Tumor with diameter of \>5cm in one dimension on T2/FLAIR. * Tumor that in the opinion of the site investigator shows significant mass effect in either the brain or spine. Note that patients with metastatic or multi-focal disease (with exception of bone marrow) are eligible as long as no sites of disease meet above criteria for bulky disease.
• 3 Breast-feeding Nursing mothers are excluded from this study. There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Lutathera.
• 4 Concurrent Illness * Patients with a history of any other malignancy, except patients with a secondary brain tumor if the patient's prior malignancy has been in remission for at least 5 years from the end of treatment. * Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction), that in the opinion of the investigator would compromise the patient's ability to tolerate protocol therapy, put them at additional risk for toxicity or would interfere with the study procedures or results. * Patients with type I diabetes.
• 5 Concomitant Medications * Patients who are receiving any other anti-cancer or investigational drug therapy are ineligible. * Prior or current treatment with 177Lu-DOTATATE/TOC or 90Y-DOTATATE/TOC.
• 6 Prisoners will be excluded from this study.
• 7 Inability to participate: Patients who in the opinion of the investigator are unwilling or unable to return for required follow-up visits, obtain follow-up studies required to assess toxicity to therapy, or adhere to drug administration plan, other study procedures, and study restrictions.
• Inclusion of Women and Minorities Both males and females of all races and ethnic groups are eligible for this study.
DRUG: LUTATHERA® (Lutetium Lu 177 dotatate)
High Grade Glioma, Meningioma, Embryonal Tumor, Medulloblastoma, Anaplastic Ependymoma, Recurrent Diffuse Intrinsic Pontine Glioma, Recurrent Malignant Glioma, Recurrent Medulloblastoma, Recurrent Primary Central Nervous System Neoplasm, Refractory Diffuse Intrinsic Pontine Glioma, Refractory Malignant Glioma, Refractory Medulloblastoma, Refractory Primary Central Nervous System Neoplasm
Somatostatin Receptor, DOTATATE, Lutathera
Tuberous Sclerosis Complex and Lymphangioleiomyomatosis Pregnancy Registry (TSC-LAM Registry)
Molly Griffith - molly.griffith@cchmc.org
FEMALE
NCT06160310
Inclusion Criteria:
* A pregnant woman with a clinical or genetic diagnosis of TSC as determined by the 2021 Consensus Guidelines (1)
* A pregnant woman with a diagnosis of LAM
* A pregnant woman with a variant of uncertain significance in TSC 1 or TSC 2
* A pregnant woman who is pregnant and the fetus has a 50% chance of TSC as deemed by the PI or Sub-Is
* A pregnant woman whose fetus is found to have concern for TSC secondary to rhabdomyomas, tubers, or congenital subependymal giant cell astrocytoma.
* An infant born to an enrolled individual.
Exclusion Criteria:
* A pregnant woman without TSC who has used preimplantation genetic testing for TSC unless qualifies under inclusion criteria #4.
* Infants diagnosed with TSC whose birth mother was not enrolled. Tuberous Sclerosis Complex, Lymphangioleiomyomatosis
Tuberous Sclerosis Complex, TSC, Lymphangioleiomyomatosis, LAM