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340 Study Matches
A Long-term Extension (LTE) Study of Guselkumab in Pediatric Participants (TRILOGY)
Megan Megan Quinlan-Waters - Megan.Quinlan-Waters@cchmc.org
ALL
3 years and over
PHASE3
NCT06663332
Inclusion Criteria:
* Must have completed the dosing planned in the primary pediatric guselkumab study
* Must have received benefit from continued guselkumab therapy in the opinion of the investigator
* Before enrollment, a participant must be either: (a) Not of childbearing potential, OR (b) Of childbearing potential and not sexually active, practicing abstinence or a highly effective method of contraception and agrees to remain on a highly effective method while receiving study intervention and until 12 weeks after the last dose - the end of relevant systemic exposure
* Parent(s) (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to allow the child to participate in the study. Assent is required from participants who are capable of understanding the nature of the study, typically those aged 7 years and older, to ensure their willingness to participate. An adolescent who provides assent will have the opportunity to sign an adult ICF upon reaching the age of majority, thereby affirming their understanding of the study's purpose and procedures, as well as their willingness to participate.
Exclusion Criteria:
* Participant is greater than or equal to (\>=) 18 years of age and resides in a country where 2 years have elapsed post marketing authorization for the respective adult indication
* Participant is \<18 years of age and resides in a county where 2 years have elapsed post marketing authorization for the respective pediatric indication
* Are pregnant, nursing, or planning pregnancy or fathering a child
* Have taken any disallowed therapies before the planned first long-term extension (LTE) dose of study intervention
* Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator
* Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant or that could prevent, limit, or confound the protocol-specified assessments DRUG: Guselkumab
Crohns Disease, Colitis, Ulcerative, Arthritis, Psoriatic, Arthritis, Juvenile
Comparative Effectiveness of Available Treatments for Sinus and Ear Infections in Children (Acute Otitis Media) (MEASURE)
Jane Luce, MPH - lucej2@upmc.edu
ALL
6 months to 36 months old
PHASE4
NCT07730814
Inclusion Criteria
* Age 6 months to \<36 months.
* Clinical diagnosis of AOM.
Exclusion Criteria
* Known allergy or other contraindication to oral amoxicillin or clavulanate
* Prior use of systemic antibiotics in the last 7 days
* History of renal impairment
* History of hepatic impairment
* Phenylketonuria or allergy to aspartame
* History of craniofacial abnormalities
* Concurrent bacterial infection requiring systemic antibiotic therapy (e.g., pneumonia, streptococcal pharyngitis)
* Ill appearance, systemic toxicity, or immunodeficiency
* Incomplete pneumococcal vaccination, defined as receipt of fewer than three doses of a pneumococcal conjugate vaccine
* Parent or caregiver unable to complete study surveys in English or Spanish
* Previous randomization into either MEASURE trial within the last 6 months
* Mastoiditis
* Conjunctivitis
* Temperature ≥39°C and AOM-SOS score ≥35
* Cochlear implants
* Spontaneous tympanic membrane perforation with otorrhea at presentation (participants who develop perforation and otorrhea after consent remain eligible)
DRUG: Amoxicillin, DRUG: Amoxicillin-Clavulanate, DRUG: Amoxicillin Placebo, DRUG: Amoxicillin-Clavulanate Placebo
Acute Otitis Media (AOM)
Ear Infection, AOM, Acute Otitis Media
Evaluation of SPN-812 (Viloxazine Extended-release Capsule) in Preschool-age Children With ADHD
ADHDResearch@cchmc.org
ALL
48 months to 69 months old
PHASE4
NCT04781140
Inclusion Criteria:
• Is male or female 4 years 0 months of age to less than or equal to 5 years 9 months of age at Visit 1 (Screening) and considered medically healthy.
• Subject's parent(s) or legal guardian(s)/representative(s) is (are) willing and able to provide written informed consent before completing any study related procedures.
• Has a primary diagnosis of ADHD according to DSM-IV-TR criteria and confirmed with the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL).
• Has an ADHD-RS-IV-P Total Score of ≥ 28 (males) or ≥ 24 (females) at Visit 1 (Screening) and at Visit 2 (Baseline).
• Has a CGI-S score of ≥ 4 (moderate or worse) at Visit 1 (Screening) and at Visit 2 (Baseline).
• Has undergone an adequate course of non-pharmacologic treatment or is having symptoms severe enough to warrant pharmacologic treatment without prior non-pharmacologic treatment.
• Is participating in a structured group activity (e.g., preschool, kindergarten, sports, Sunday school, summer camp or childcare program) at least 2 days a week during study so as to assess symptoms and impairment in a setting outside the home.
• Has not initiated any behavioral intervention/therapy within 30 days of Visit 1 (Screening) and does not plan to initiate any new or discontinue any ongoing behavioral intervention/therapy during the study (e.g., subject is eligible if behavioral intervention/therapy is initiated 30 or more days prior to Visit 1 \[Screening\] and continues with a similar duration/frequency throughout their study).
• Subjects who are on ADHD medication at Visit 1 (Screening), but whose ADHD symptoms are not well controlled on current ADHD medication (e.g., meets Inclusion Criterion #4), meet all other inclusion/exclusion criteria, and discontinues ADHD medication at least 7 days prior to the day of Visit 2 (Baseline) are eligible to participate.
• Has no current condition in the opinion of the Investigator that could confound efficacy assessments, safety assessments or increase participant risk.
• Has lived with the same parent(s) or legal guardian(s) or has lived under a shared living arrangement (e.g., joint legal custody) for greater than or equal to 6 months prior to Visit 1 (Screening).
• Has a body weight ≥5th percentile for age and sex at Visit 1 (Screening) and Visit 2 (Baseline).
Exclusion Criteria:
• Has a diagnosis at Screening (per K-SADS-PL) of another psychiatric disorder that is considered to be the primary diagnosis rather than ADHD or has a comorbid psychiatric disorder secondary to ADHD that, in the opinion of the investigator (after consulting medical monitor), will likely interfere with study treatment adherence and/or impact study results.
• Has a current diagnosis of a major neurological disorder. The eligibility of those who have seizures, a history of seizure-like events (e.g., syncope, myoclonus, severe muscle spasms), a family history of seizure disorder (immediate family, i.e., sibling, parent), and/or febrile seizures will be assessed on a case-by-case basis after consulting the medical monitor.
• History of Bipolar Disorder diagnosed in a first degree relative.
• Has global development delay or intellectual disability by medical history.
• Has a current diagnosis of a significant (per Investigator's evaluation and/or judgement) systemic disease.
• Has body mass index \> 95th percentile for the subject's age and sex at Visit 1 (Screening) or Visit 2 (Baseline).
• Has a mean resting systolic and diastolic blood pressure\* that are both \>95th percentile for age sex, and height and has a mean resting pulse rate\* that is \>95th percentile for age and sex (males: \>117 bpm; females: \>122 bpm) at Visit 1 (Screening) or Visit 2 (Baseline). \* Note: The mean of three measurements while seated.
• Has a clinically significant electrocardiogram finding(s) at Visit 1 (Screening).
• Is currently taking SPN-812 for ADHD, has previously taken SPN-812 for ADHD, but discontinued due to a lack of efficacy or adverse reactions, or has history of allergic reaction, hypersensitivity or intolerance to viloxazine.
• Has an allergy to or cannot swallow pudding and applesauce and cannot swallow intact capsule whole.
• Has any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the subject's participation in the study.
• Has received any investigational drug within the longer of 30 days or 5 half-lives prior to Visit 2 (e.g., first dose of study medication).
• Has a positive urine drug test at Visit 1 (Screening). A positive test for amphetamines is allowed for subjects receiving a stimulant ADHD medication at Screening. The subject will be required to discontinue the stimulant for the duration of the study, beginning at least 7 days prior to Visit 2 (Baseline).
• Is using of prohibited concomitant medications including known CYP1A2 substrates (e.g., theophylline, melatonin) during the Screening Period or (anticipated) for the duration of the study.
• Any reason that, in the opinion of the Investigator, would prevent the subject from participating in the study.
• Has suicidal ideation ("Yes" indicated on C-SSRS question 4 or 5) or suicidal behavior ("Yes" indicated on C-SSRS for any suicidal behavior) within 6 months prior to or the day of Visit 1 (Screening) or has attempted suicide ("Yes" indicated on C-SSRS for lifetime).
DRUG: 100mg SPN-812, DRUG: Placebo
Attention-Deficit/Hyperactivity Disorder
ADHD
CorMatrix Cor TRICUSPID ECM Valve Replacement Study
Isabella Aspromonte - Isabella.Aspromonte@cchmc.org
ALL
1 year to 85 years old
NA
NCT02397668
Inclusion Criteria:
• Patient with a regurgitant or absent tricuspid valve requiring surgical treatment including those patients having concomitant cardiac procedures
• Male or female
• Patient/authorized legal guardian understands the nature of the procedure, is willing to comply with associated follow-up evaluations, and provides written informed consent and the pediatric patient (if applicable) provides written assent (if able) prior to procedure
• Patient/patient's authorized legal guardian is geographically stable (or willing to return for required study follow-up) and understands and is willing to fulfill all of the expected requirements of this clinical protocol
• Children with congenital disease where the Cor PEDIATRIC Tricuspid ECM Valve would be the physiological right-sided valve
Exclusion Criteria:
• Tricuspid annulus too small (\< 10mm) to accommodate the Cor Tricuspid ECM Valve
• Left ventricular ejection fraction (LVEF) \< 25%
• Mean pulmonary pressure \> 50mm Hg or pulmonary vascular resistance greater than 6 Woods Units
• Emergency cardiac procedure. An example would be a person requiring resuscitation and in cardiogenic shock. An unscheduled or unplanned emergency surgery
• Cardiac transplant patient
• Acute transmural myocardial infarction (MI) within 7 days of enrollment that results in cardiogenic shock
• Patients with a single ventricle where the Cor Tricuspid ECM Valve would be the systemic AV valve
• Documented primary coagulopathy or uncorrected platelet disorder, including thrombocytopenia (absolute platelet count \<30k). Patient can be enrolled regardless of these parameters if in the opinion of the Investigating Surgeon the coagulopathy can be adequately reversed by transfusions. An example would be the reversal of thrombocytopenia by transfusion of platelets
• Documented evidence of intrinsic hepatic disease (defined as liver enzyme values (aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin) that are \> 5 times the upper limit of reference range within 30 days of enrollment, except in association with acute/reversible decompensation as determined by the Investigator)
• Documented evidence of significant renal dysfunction (serum creatinine \> 4.0mg/dl or GFR\< 30 on the modified Schwartz formula)
• Stroke within 30 days prior to enrollment
• Major or progressive non-cardiac disease (liver failure, renal failure, cancer (CA)) that has a life expectancy of less than one year
• Known cancer (cancer-free \<1 year; does not include non-metastatic basal cell carcinoma or cervical carcinoma) and/or undergoing treatment including chemotherapy and radiotherapy
• Hematological disorders (e.g., aplastic anemia) or patients taking bone marrow suppressant drugs
• Known sensitivity to porcine materials
• Contraindication to anticoagulation/antiplatelet therapy (aspirin (ASA) and/or Plavix)
• Patients who are pregnant (method of assessment Investigator's discretion)
• Patients who are currently enrolled in another investigational study or registry that would directly impact the treatment or outcome of the current study, without CorMatrix written approval
DEVICE: CorMatrix Cor TRICUSPID ECM Valve
Tricuspid Valve Disease
Use of Hyperpolarized 129Xe MR Lung Imaging in Adults for Calibration (HpXeMRCal)
Ana Mort - ana.mort@cchmc.org
ALL
18 years and over
PHASE1
NCT02316379
Inclusion Criteria:
* Adults ages 18 years and older
* Participant must be able to hold their breath for up to 16 seconds
Exclusion Criteria:
* History of heart defect
* Pregnancy or positive pregnancy test
* History of uncontrolled asthma defined for this study as requiring use of rescue inhaler ≥ 2 times in past month.
* Symptoms of respiratory infection (loose or productive cough or wheeze), chest tightness, or sinus infection within past week.
* Baseline oximetry at MRI visit of less than 95% on room air or less than 95% on a previously prescribed dosage of oxygen delivered by nasal cannula.
* Participant is claustrophobic and unable to tolerate the imaging.
* Standard MRI exclusions (metal, implants). DRUG: Hyperpolarized 129 Xenon, DEVICE: MRI
Respiratory Disorders
Respiratory
Randomized Study in Children and Adolescents With Migraine: Acute Treatment
Michelle Shin - michelle.shin@cchmc.org
ALL
6 years to 17 years old
PHASE3
NCT04649242
Inclusion Criteria:
• History of migraine (with or without aura) for \> 6 months before Screening according to the IHS Classification ICHD-319 specifications for pediatric migraine. History may be verified using both medical records and recall by the participant and/or participant's parent(s)/legal representative(s).
• History of 1 to 8 moderate or severe attacks per month during the 2 months prior to enrollment, with attacks lasting \> 3 hours without treatment, and attacks occurring at intervals \> 24 hours.
• Prophylactic migraine medication are permitted if the dose has been stable for at least 12 weeks prior to the Baseline Visit, and the dose is not expected to change during the course of the study.
• Participants may remain on one (1) medication with possible migraine prophylactic effects, excluding CGRP antagonists \[biologic or small molecule\], during the treatment phases.
• Concomitant use of a CGRP antagonist, such as erenumab or fremanezumab, is prohibited.
• Previously discontinued prophylactic migraine medication must have done so at least 90 days prior to the Screening Visit.
• Verbally distinguish between migraine and other types of headaches.
• Participants must have a weight \> 40 kg at the Screening Visit.
• Adequate venous access for blood sampling.
• Male and female participants ≥ 6 to \< 18 years of age (participants must not reach their 18th birthday during the study).
Exclusion Criteria:
• History of cluster headache or hemiplegic migraine headache.
• Confounding and clinically significant pain syndrome that may interfere with the participant's ability to participate in this study.
• Current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6 months prior to the Screening Visit. Participants with a lifetime history of psychosis and/or mania.
• History of suicidal behavior or major psychiatric disorder.
• Current diagnosis or history of substance abuse; positive drug test at Screening.
• History of moderate or severe head trauma or other neurological disorder (including seizure disorder) or systemic medical disease that is likely to affect central nervous system functioning.
• Recent or planned surgery, requiring general anesthesia, \<8 weeks prior to the Screening Visit.
• Participant has had gastrointestinal surgery that interferes with physiological absorption and motility (i.e., gastric bypass, duodenectomy, or gastric banding).
• Current diagnosis of viral hepatitis or a history of liver disease.
• Conditions considered clinically relevant in the context of the study such as uncontrolled hypertension (high blood pressure), diabetes, a life-threatening allergy
DRUG: Rimegepant/BHV3000, DRUG: Matching placebo
Pediatric Migraine
Migraine, Acute treatment, Phonophobia, Photophobia, Nausea, Pediatric, Children, Adolescent, Pediatric Migraine
A Study of Emapalumab for Pediatric Aplastic Anemia
Anthony Sabulski, MD - anthony.sabulski@cchmc.org
ALL
0 years to 25 years old
PHASE2
NCT06430788
Inclusion Criteria:
* Patients undergoing workup for suspected newly diagnosed sAA:
* Patients with severe cytopenias and a hypocellular marrow concerning for sAA
* Patients that meet the definition for suspected sAA (Camitta Criteria) as follows:
Marrow Cellularity: \<25%, or 25-50% with \<30% residual hematopoietic cells Peripheral cytopenias (at least 2 of 3) Absolute neutrophil count (ANC): \<500 x 10\^9/L Platelets: \<20 x 10\^9/L Absolute Reticulocyte Count: \<60 x 10\^9/L
* Patients that do not have evidence of leukemia or MDS
* Patients \< 25 years of age at time of diagnosis
* Able to tolerate emapalumab and IST (with standard institutional organ function criteria)
Exclusion Criteria:
* Uncontrolled infection at presentation.
* Patients who have undergone previous treatment for sAA.
* Patients with known inherited bone marrow failure
* Patient who has completed a full workup for sAA including having results back from telomere testing, DEB and genetics (when applicable), as well as having an appropriate willing and available donor and would otherwise be admitted for HSCT within 2 weeks of enrolling on the trial
* Patients with leukemia or MDS
* Patient or parent or guardian unable to give informed consent or unable to comply with the treatment protocol including research tests. BIOLOGICAL: Emapalumab
Aplastic Anemia, Cytopenia, Hypocellular Marrow
pediatric aplastic anemia, aplastic anemia, cytopenia, hypocellular marrow, Emapalumab, Memorial Sloan Kettering Cancer Center, 23-278
Nafamostat Efficacy in Phase 3 Registrational CRRT Study (NEPHRO)
IIham IIham Boutahri - Ilham.Boutahri@cchmc.org
ALL
18 years to 80 years old
NA
NCT06150742
Inclusion Criteria:
* Patients requiring CRRT or undergoing CRRT initiated within the prior 48 hours
* Patients who cannot tolerate heparin or are at high risk of bleeding
Exclusion Criteria:
* Patients weighing less than 50 kg
* Patients receiving systemic anticoagulation
* Patients with active bleeding DEVICE: Niyad (nafamostat mesylate), DEVICE: Placebo (0.9% NaCl)
Acute Kidney Injury
continuous renal replacement therapy, anticoagulation
Office, Home, and Ambulatory Blood Pressure (HBPA)
Marissa Donaldson - marissa.donaldson@cchmc.org
ALL
6 years to 19 years old
NCT05297708
Inclusion Criteria:
• Age 6 years to \<19 years old;
• Elevated blood pressure defined as 15% lower than the 95%ile BP based on clinical practice guidelines(CPG) but less than stage II hypertension based on CPG;
• Tolerate ABPM 24 hours;
• Tolerate HBP; and
• Can have diabetes mellitus, obstructive sleep apnea, and attention deficit hyperactivity disorder managed by medication.
• On stable doses of medications known to affect BP such as:
• Corticosteroids
• Calcineurin inhibitors
• Oral decongestants;
• Clinically stable
Exclusion Criteria:
• On antihypertension medications or treated in the last 6 months;
• Pregnant;
• Structural heart disease such as:
• Obstructive valvular disease
• Coarctation of the aorta
• Cardiomyopathy;
• Other secondary causes such as:
• Renal artery stenosis
• Neurological condition with dysautonomia;
• Recent initiation of medications known to affect BP such as:
• Corticosteroids
• Calcineurin inhibitors
• Oral decongestants;
Elevated Blood Pressure
Pharmacokinetic Study of Venetoclax Tablets Crushed and Dissolved Into a Solution
- cancer@cchmc.org
ALL
0 years to 38 years old
NCT06131801
Inclusion Criteria:
* Age: Patients must be \<39 years of age at time of study enrollment
* Diagnosis: Patients may have a diagnosis of any hematologic malignancy
* Central access: Patients must have an existing venous or arterial access line for PK blood draws
* Weight requirement: Patients must weigh at least 5.5 kg at the time of enrollment
* Venetoclax: Patients must be receiving any dose of venetoclax given as a solution made from crushed tablets by mouth (PO) or via nasogastric (NG), or G-tube as prescribed by their treating oncologist.
* Concurrent chemotherapy medications: Patients may receive venetoclax as a single agent or in combination with any other chemotherapeutic agents.
Exclusion Criteria:
* Pregnant women are excluded from this study because venetoclax has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with venetoclax, breastfeeding should be discontinued if the mother is treated with venetoclax.
* Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method while on study treatment and for six months following completion. OTHER: 1. Drug: The Venetoclax PK study is collecting bodily fluid samples (ie., whole blood and optional cerebrospinal fluid) of patients prescribed venetoclax as crushed tablets per standard of care.
Hematologic Malignancy, Leukemia, Lymphoma, Acute Lymphocytic Leukemia, ALL, Acute Myelogenous Leukemia, AML, Chronic Myelogenous Leukemia, CML, Myeloproliferative Neoplasm, Non Hodgkin Lymphoma, Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Burkitt Lymphoma, T-cell Lymphoma, B Cell Lymphoma, Peripheral T Cell Lymphoma, Cutaneous B-Cell Lymphoma
Venetoclax, Pediatric AML, Pediatric Relapsed/Refractory AML
A Phase 2 Study of WU-CART-007, an Anti-CD7 Allogeneic CAR-T Cell Therapy in T-Cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma (T-RRex)
Monica Trapp - monica.trapp@cchmc.org
ALL
6 month(s) and over
PHASE2
NCT06514794
Key
Inclusion Criteria:
* Disease Criteria: Evidence of T-ALL or T-LBL, as defined by World Health Organization (WHO) classification, and either relapse/refractory or MRD positive
* Age: Lower age limit of ≥ 6 months; adequate organ function
* Eastern Cooperative Oncology Group (ECOG) 0 or 1/Karnofsky Performance Status 70 and above at Screening.
Key Exclusion Criteria:
* Prior treatment with any anti-CD7 therapy.
* Patients with decompensated hemolytic anemia.
* Presence of Grade 2 to 4 acute or extensive chronic GvHD requiring systemic immunosuppression. Grade 1 GvHD not requiring immunosuppression or Grade 2 skin GvHD if treated with topical therapy only are acceptable. BIOLOGICAL: WU-CART-007
T-cell Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma
CAR-T Therapy, Acute Leukemia
ACT001 for the Treatment of Diffuse Intrinsic Pontine Gliomas and H3K27-altered High Grade Gliomas
- cancer@cchmc.org
ALL
12 months to 39 years old
PHASE2
NCT06838676
Inclusion Criteria:
• Patients must be ≥ 12 months and ≤ 39 years of age at the time of study enrollment.
• Diagnosis: * Cohort A: Newly Diagnosed DIPG * Patients with newly-diagnosed DIPG with typical MRI findings (tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons) with or without biopsy and have completed radiation therapy (RT) within 28 to 35 calendar day prior to start of therapy. * Patients must have started RT \<42 calendar days from radiographic diagnosis (for non-biopsied DIPG patients only) or definitive surgery, whichever is later. * If a biopsy was performed, the date of surgical biopsy will be considered the date of definitive diagnostic surgery; if a patient underwent two upfront surgeries \[e.g., biopsy then debulking\], this is the date of the second surgery) * Cohort B \[ENROLLMENT PAUSED\]: progressive/recurrent DIPG or H3K27-altered HGG OR refractory disease * Patients with DIPG (no biopsy required), pathologically-confirmed (at diagnosis or recurrence) H3K27-altered DIPG, or extra-pontine H3K27-alteredHGG who have progressive/recurrent or refractory disease * Progressive/recurrent: patients who have progressive or recurrent disease following frontline treatment must have included at least focal RT. New lesions since completion of frontline RT qualify as progressive disease. * Refractory disease is defined as: Presence of persistent, measurable, abnormality on conventional MRI that is further distinguished by histology or advanced imaging, OR as determined by the treating physician and discussed with the Study Chair(s) prior to enrollment. * Patients with H3K27-altered spinal HGG are eligible. * Patients with metastatic disease are eligible.
• Disease Status * Cohort A: patients may have any disease status but must have completed initial radiation therapy (RT) before enrollment. * Cohort B: Patients must have measurable disease assessable by MRI. Patients may have extra neuronal disease.
• Performance Level: Karnofsky Performance Scale score ≥ 50% for patients \> 16 years of age and Lansky Performance Scale score \> 50% for patients ≤ 16 years of age (applies to all patients) Note: Patients who are unable to walk because of paralysis, but who are capable of using a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior anti-cancer therapy: * For Cohort A ONLY: * Surgery, radiation (focal to disease) and/or steroids (dexamethasone with goal to wean dexamethasone throughout protocol therapy) are permissible. Temozolomide administered concurrently with RT is permissible. Bevacizumab use is permitted given the last dose was administered \>/= 21 days prior to enrollment. No other prior anticancer therapy for DIPG will be allowed. * Patients must enroll and start treatment on study between 28 and 35 calendar days post-completion of RT. * Patients must have started RT \<42 calendar days of initial diagnosis (defined as the date of diagnostic biopsy or resection; if a patient underwent two upfront surgeries \[e.g., biopsy then resection or debulking\], this is the date of the second surgery). * Radiotherapy must have been administered at standard dose of 54 Gy for DIPG patients. Any variances in the radiotherapy dose within 10% of the standard doses outlined above will be discussed with the Study Chair to confirm eligibility prior to study enrollment. * For Cohort B ONLY: Patients must have fully recovered from the acute treatment related toxicities (defined as \ 6 months (such as ifosfamide-related proteinuria) may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the Investigator and Sponsor.) The wash out period between the prior anti-cancer chemotherapy, and enrollment must be:
• Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea).
• Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g. Neulasta) or 7 days for short-acting growth factor.
• Biologic (anti-neoplastic agent): At least 7 days after the last dose of a biologic agent. 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. The duration of this interval must be discussed with the study chair.
• Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
• Monoclonal antibodies: \> 21 days must have elapsed from the infusion of last dose of antibody
• Radiation therapy: * All Cohort B patients: Patients must have received their last fraction of focal irradiation to new sites of progressive disease \> 14 days prior to enrollment. * Patients who received CSI must have received their last fraction \> 3 months prior to enrollment. * Progressive/recurrent disease: Patients who received re-irradiation to primary disease must have received their last fraction \> 3 months prior to study enrollment. * Refractory Disease: * Patients must have completed frontline RT \> 6 months prior to enrollment. * Patients who received re-irradiation to primary disease must have received their last fraction \> 3 months prior to study enrollment.
• Stem Cell Transplant: Patients must be ≥ 3 months since autologous stem cell transplant. Patients who received allogenic stem cell transplant or solid organ transplant are not eligible for study
• Organ Function Requirements (applies to all patients)
• 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)
• Adequate renal function defined as: * Creatinine clearance or radioisotope GFR ≥ 70 mL/min/1.73 m² or * A serum creatinine based on age/gender as follows (Schwartz et al. J. Peds, 106:522, 1985): Age Maximum Serum Creatinine (mg/dL) Male Female 1 to \< 2 years 0.6 0.6 2 to \< 6 years 0.8 0.8 6 to \< 10 years 1.0 1.0 10 to \< 13 years 1.2 1.2 13 to \< 16 years 1.5 1.4 ≥ 16 years 1.7 1.4
• Adequate liver function defined as: * total bilirubin must be \ • Adequate cardiac function defined as: * Ejection fraction of ≥ 50% by echocardiogram * QTc ≤ 450 msec (by Bazett formula)
• For Cohort B: Adequate neurologic function defined as: * Patients with seizure disorders may be enrolled if seizures are well- controlled. Well controlled is defined by no increase in seizure frequency in the 7 days prior to enrollment. * Patients with neurological deficits should have deficits that are stable for at least the 7 days prior to enrollment.
• 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.
• Absence of other clinically significant concomitant active medical disorder, based on the investigator's judgement.
Exclusion Criteria:
A patient who meets any of the following exclusion criteria will not be eligible in the study (Applies to both cohorts except where noted below):
• Cohort A only: Patients with metastatic disease.
• Concomitant medications: * Corticosteroids: * Cohort A - Patients receiving corticosteroids are eligible regardless of dosing * Cohort B - Patients receiving corticosteroids who have been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are eligible * Anti-cancer Agents: Patients who are currently receiving other anti-cancer agents are not eligible (Refer study inclusion criteria relating to anti-cancer therapies) * Cohort A - Patients that have received any anti-cancer treatment other than surgery, RT, temozolomide concurrent with RT, and/or previous bevacizumab with appropriate washout period are not eligible. * Investigational Drugs: Patients who are currently receiving another investigational drug are not eligible. * Anticonvulsants should be used as clinically indicated. The use of enzyme inducing anticonvulsants is not permitted * LHRH agonist / antagonists are not permitted * High Dose Biotin (B7) supplements are not permitted
• Concomitant medications used with caution: selective serotonin reuptake inhibitor (SSRI) such as Lexapro, Fluoxetine (Prozac), fluvoxamine (Luvox), paroxetine (Paxil), sertraline (Zoloft), citalopram (Celexa), and escitalopram should be used with caution.
• Infection: Patients who currently have an uncontrolled infection (in the opinion of the PI) are not eligible.
• Patients who have received a prior solid organ transplantation are not eligible.
• 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 postmenarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
• Patients of childbearing or child fathering potential must agree to use adequate contraceptive methods (hormonal or barrier method of birth control; abstinence) while being treated on this study and for 3 months after completing therapy. Note: The definition of effective contraception will be based on the judgement of the principal investigator or a designated associate.
• Patients who are in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Patients who have previously received either ACT001 or parthenolide are not eligible.
DRUG: ACT001
Diffuse Intrinsic Pontine Gliomas (DIPG), Progressive DIPG, Refractory DIPG, Recurrent DIPG, H3K27-altered High Grade Glioma
High Grade Glioma, Diffuse Intrinsic Pontine Glioma
Spastic Paraplegia - Centers of Excellence Research Network (SP-CERN)
Karlee Migneault - Karlee.Migneault@cchmc.org
ALL
NCT06553976
Inclusion Criteria:
* Male or female patients of all ages with a clinical and molecular diagnosis of hereditary spastic paraplegia type 4 (SPG4, SPAST) or hereditary spastic paraplegia type 5A (SPG5A, CYP7B1).
Exclusion Criteria:
* Not having such a diagnosis and/or not being related to such individual. Hereditary Spastic Paraplegia, Primary Lateral Sclerosis, SPG4, SPG5A, Spastic Paraplegia 4, Spastic Paraplegia 5A, Early Onset Hereditary Spastic Paraplegia, Neuromuscular Diseases, Spastic Paraplegia, Hereditary
Streamlined Treatment of Pulmonary Exacerbations in Pediatrics (STOP PEDS RCT)
Sharon Kadon - sharon.kadon@cchmc.org
ALL
3 years to 18 years old
NA
NCT06654752
Inclusion Criteria:
• Age
• For main cohort and non-HEMT cohort: age 6 to \<19 years
• For preschool cohort: age 3 to \<6 years
• Documentation of a CF diagnosis as evidenced by one or more clinical features consistent with the CF phenotype and one or more of the following criteria:
• sweat chloride ≥ 60 mEq/liter
• two disease-causing variants in the cystic fibrosis transmembrane conductive regulator (CFTR) gene
• Written informed consent (and assent when applicable) obtained from participant or participant's legal representative and ability of participant to comply with the requirements of the study
• Highly Effective Modulator Therapy
• For main cohort and preschool cohort: Taking HEMT for at least 3 months at enrollment
• For non-HEMT cohort: not eligible for HEMT based on CFTR genotype or eligible but not taking for at least 3 months and no plans to start HEMT in the next year, and also not taking tezacaftor-ivacaftor or lumacaftor-ivacaftor for at least 3 months
• For main cohort and non-HEMT cohort: able to perform acceptable and reproducible spirometry
• For main cohort and non-HEMT cohort: ppFEV1 ≥ 50% predicted at enrollment based on the Global lung Initiative (GLI) reference equations
• Ability to receive text messages and access the internet
Exclusion Criteria:
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the individual or the quality of the data
• Receiving an acute course of oral or IV antibiotics at the time of enrollment or within the 14 days prior to enrollment. Individuals may be re-screened ≥21 days after completion of antibiotics if they are at their baseline state of health, per self-report
• Treatment with systemic corticosteroids at enrollment or within the 14 days prior to enrollment. Individuals may be re- screened ≥21 days after completion of systemic corticosteroids if they are at their clinical baseline, per self-report
• History of solid organ transplant
• History of positive culture for Mycobacterium abscessus in the 12 months prior to enrollment
• Treatment with antibiotics for any non-tuberculous mycobacteria (NTM) at enrollment
• Three or more IV antibiotic-treated PEx in the 12 months prior to enrollment
• Treatment with chronic oral antibiotics other than azithromycin at enrollment
• Treatment with systemic corticosteroids for allergic bronchopulmonary aspergillosis (ABPA) in the 12 months prior to enrollment
OTHER: Immediate Oral Antibiotics, OTHER: Tailored Treatment: Oral Antibiotics only if Additional Treatment needed
Cystic Fibrosis
cystic fibrosis, oral antibiotics, pulmonary exacerbation, pediatric
The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) Study (PLUMM)
Catherine Robben - catherine.robben@cchmc.org
ALL
8 years to 20 years old
PHASE2
NCT05538208
Inclusion
• Male or female aged 8 to \< 21 years;
• Must meet Classification Criteria for SLE as per the criteria of the American College of Rheumatology (ACR)/ European League Against Rheumatism
• Diagnosed with proliferative LN as per the International Society of Nephrology/Renal Pathology Society4 based on kidney biopsy done within 90 days prior to enrollment into the study; Subjects may have been previously diagnosed with LN. For study inclusion, the kidney biopsy must be interpreted as one of the following classes: Class 3, Class 3/5, Class 4, or Class 4/5.
• Treatment of LN with twice daily MMF as per the decision of the treating physician. The subject will have taken MMF as prescribed by their treating physician for a minimum of 4 days (or 8 doses).
• Subject tolerates MMF as per the treating physician's opinion;
• Able to swallow MMF tablets and capsules;
• If subject is treated with belimumab, must be IV or SQ;
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
• Evidence of a personally signed and dated Informed Consent document and Assent document (as appropriate) indicating that the subject and a legally acceptable representative/ parent(s)/legal guardian has been informed of all pertinent aspects of the study.
• Parent or legal guardian must have a smart phone available and able to support the PLUMM smart phone application.
• Must be able to complete study questionnaires in English or Spanish.
• Perceived or stated inability to adhere to the study protocol;
• Hypersensitivity to MMF or any component of the drug product;
• Presence of features (from SLE or other chronic disease) that a-priori suggest that the subject benefits from other therapies than that suggested or allowable by the study protocol; These disease features include but are not limited to severe, progressive, or uncontrolled hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
• History of other kidney disease besides LN or prior to the diagnosis of SLE;
• Need for renal replacement therapy within 2 weeks from Baseline Subjects can have required short-term renal replacement therapy prior to Baseline, for example due to preceding acute kidney injury.
• Infections:
• Untreated latent or active tuberculosis (TB);
• Chronic infections requiring treatment;
• A subject known to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B;
• Diagnosis of any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within 4 weeks prior to Baseline visit;
• Any treated infections within 2 weeks of Baseline visit;
• History of infected joint prosthesis with prosthesis still in situ;
• Blood dyscrasias, including:
• Hemoglobin \<8.5 g/dL or Hematocrit \<22%;
• White Blood Cell count \<2.6 x 109/L;
• Neutrophil count \<1.2 x 109/L;
• Platelet count \<100 x 109/L;
• Lymphocyte count \<0.5 x 109/L.
• 8\) Estimated glomerular filtration rate \[GFR\] \<40 mL/min/1.73 m2 calculated using the CKiD U25 equation (see Appendix 4);
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times the upper limit of normal;
• Vaccinated or exposed to a live or attenuated vaccine within the 4 weeks prior to Baseline visit;
• History or current symptoms suggestive of lymphoproliferative disorders (e.g., Epstein Barr Virus \[EBV\] related lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma);
• Current malignancy or history of any malignancy with the exception of adequate treated or excised basal cell or squamous cell or cervical cancer in situ;
• Recent (within 4 weeks prior to Baseline visit) significant trauma or major surgery;
• Herbal supplements with pharmaceutical properties must be discontinued at least 1week prior to Baseline visit, unless there are sufficient data available regarding the duration of an herbal medication's pharmacokinetic and pharmacodynamic effects to allow a shorter or longer washout to be specified (e.g., 5 half-lives).
• Oral or intravenous cyclophosphamide must be discontinued 12 weeks prior to Baseline visit
• Use of prohibited prescription medication as listed in Appendix 3 within the specified time frame prior to Baseline visit
• Participation in other studies involving investigational drug(s) within 4 weeks or 5 half-lives (whichever is longer) prior to Baseline visit and/or during study participation; Exposure to investigational biologics should be discussed with the Sponsor.
• Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use two highly effective methods of contraception or are abstinent for the duration of the study;
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
• Male or female aged 8 to \< 21 years;
• Must meet Classification Criteria for SLE as per the criteria of the American College of Rheumatology (ACR)/ European League Against Rheumatism
• Diagnosed with proliferative LN as per the International Society of Nephrology/Renal Pathology Society4 based on kidney biopsy done within 90 days prior to enrollment into the study; Subjects may have been previously diagnosed with LN. For study inclusion, the kidney biopsy must be interpreted as one of the following classes: Class 3, Class 3/5, Class 4, or Class 4/5.
• Treatment of LN with twice daily MMF as per the decision of the treating physician. The subject will have taken MMF as prescribed by their treating physician for a minimum of 4 days (or 8 doses).
• Subject tolerates MMF as per the treating physician's opinion;
• Able to swallow MMF tablets and capsules;
• If subject is treated with belimumab, must be IV or SQ;
• Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;
• Evidence of a personally signed and dated Informed Consent document and Assent document (as appropriate) indicating that the subject and a legally acceptable representative/ parent(s)/legal guardian has been informed of all pertinent aspects of the study.
• Parent or legal guardian must have a smart phone available and able to support the PLUMM smart phone application.
• Must be able to complete study questionnaires in English or Spanish.
Exclusion Criteria:
• Perceived or stated inability to adhere to the study protocol;
• Hypersensitivity to MMF or any component of the drug product;
• Presence of features (from SLE or other chronic disease) that a-priori suggest that the subject benefits from other therapies than that suggested or allowable by the study protocol; These disease features include but are not limited to severe, progressive, or uncontrolled hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
• History of other kidney disease besides LN or prior to the diagnosis of SLE;
• Need for renal replacement therapy within 2 weeks from Baseline Subjects can have required short-term renal replacement therapy prior to Baseline, for example due to preceding acute kidney injury.
• Infections:
• Untreated latent or active tuberculosis (TB);
• Chronic infections requiring treatment;
• A subject known to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B;
• Diagnosis of any infection requiring hospitalization, parenteral antimicrobial therapy or judged to be opportunistic by the investigator within 4 weeks prior to Baseline visit;
• Any treated infections within 2 weeks of Baseline visit;
• History of infected joint prosthesis with prosthesis still in situ;
• Blood dyscrasias, including:
• Hemoglobin \<8.5 g/dL or Hematocrit \<22%;
• White Blood Cell count \<2.6 x 109/L;
• Neutrophil count \<1.2 x 109/L;
• Platelet count \<100 x 109/L;
• Lymphocyte count \<0.5 x 109/L.
• 8\) Estimated glomerular filtration rate \[GFR\] \<40 mL/min/1.73 m2 calculated using the CKiD U25 equation (see Appendix 4);
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 times the upper limit of normal;
• Vaccinated or exposed to a live or attenuated vaccine within the 4 weeks prior to Baseline visit;
• History or current symptoms suggestive of lymphoproliferative disorders (e.g., Epstein Barr Virus \[EBV\] related lymphoproliferative disorder, lymphoma, leukemia, myeloproliferative disorders, or multiple myeloma);
• Current malignancy or history of any malignancy with the exception of adequate treated or excised basal cell or squamous cell or cervical cancer in situ;
• Recent (within 4 weeks prior to Baseline visit) significant trauma or major surgery;
• Herbal supplements with pharmaceutical properties must be discontinued at least 1week prior to Baseline visit, unless there are sufficient data available regarding the duration of an herbal medication's pharmacokinetic and pharmacodynamic effects to allow a shorter or longer washout to be specified (e.g., 5 half-lives).
• Oral or intravenous cyclophosphamide must be discontinued 12 weeks prior to Baseline visit
• Use of prohibited prescription medication as listed in Appendix 3 within the specified time frame prior to Baseline visit
• Participation in other studies involving investigational drug(s) within 4 weeks or 5 half-lives (whichever is longer) prior to Baseline visit and/or during study participation; Exposure to investigational biologics should be discussed with the Sponsor.
• Pregnant female subjects; breastfeeding female subjects; male subjects with partners currently pregnant; male subjects able to father children and female subjects of childbearing potential who are unwilling or unable to use two highly effective methods of contraception or are abstinent for the duration of the study;
• Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.
DRUG: Mycophenolate Mofetil, DRUG: Mycophenolate Mofetil
Lupus Nephritis
A Phase 2, Open-Label Study to Evaluate the Safety and Effects of HLX-1502 in Patients With Neurofibromatosis Type 1 (INSPIRE-NF1)
Lori Backus - lori.backus@cchmc.org
ALL
12 years and over
PHASE2
NCT06541847
Inclusion Criteria:
• All participants must have a diagnosis of NF1 based on the 2021 revised consensus criteria.
• Participants must have PN(s) that are progressive OR are causing significant morbidity, such as (but not limited to) head and neck lesions that are compromising the airway or great vessels, brachial or lumbar plexus lesions that are causing nerve compression and loss of function, lesions causing significant disfigurement (e.g., orbital lesions), lesions of the extremity that cause limb hypertrophy or loss of function, and painful lesions. Participants with paraspinal PN will be eligible for this trial. Histologic confirmation of tumor is not necessary but should be considered if there are clinical or radiographic findings concerning for malignant transformation of a PN.
• Measurable Disease: Participants must have measurable PN(s) amenable to volumetric MRI analysis. For the purpose of this study, the target lesion must be seen on at least 3 consecutive MRI slices and the field of view must contain the entire tumor of interest. Tumors must be at least 3 mL in volume (most PN 3 cm in longest diameter will meet this criteria). If the tumor is \< 3 cm in longest diameter, the participant may still be eligible. Central review of the MRI of the target PN is required prior to enrollment to ensure that the tumor is measurable and amenable to volumetric analysis.
• Age: Participants must be ≥ 12 years of age at the time of study entry. Note: Although prior MEKi therapy is not a requirement, patients should be counseled on the availability of FDA-approved MEKi therapies prior to enrollment.
• Weight ≥ 42 kg.
• Performance Level: Participants must have a Lansky (12-15 years of age) or Karnofsky (16+ years of age) score ≥ 50%.
• Organ Function Requirements: Adequate Bone Marrow Function, Adequate Renal Function, Adequate Liver Function, Normal pancreatic function: amylase and lipase levels ≤ 1.5 x ULN. Blood pressure within upper limit of normal as defined below based on the average of the 2nd and 3rd of a total of 3 consecutive measurements, 5 minutes apart. Antihypertensives are permissible to achieve blood pressure within ULN, however must be on stable antihypertensive regimen with no adjustments within 14 days of enrollment.
• Sexually active women of childbearing potential and fertile male participants and their partners must agree to use effective methods of contraception e.g., hormonal oral contraception, injectables, intrauterine device, surgical sterilization including vasectomy, or hormonal implant with barrier methods (male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment. Barrier methods alone are insufficient. True sexual abstinence or evidence of surgical sterility (e.g. vasectomized partner, post-hysterectomy, menopause with last menstrual period \>=12 months prior to screening visit) are acceptable method of birth control. Persons of childbearing potential will be given a pregnancy test within 14 days prior to first dose of study treatment and must have a negative urine or serum pregnancy test.
• The participant is not planning to undergo surgery or other interventions/ treatments for the target lesion, except protocol specified therapy, for the duration of the study.
• The participant or the participant's legal authorized representative is able to understand the informed consent form describing the risks of the study and voluntarily signs the informed consent document.
• In the opinion of the investigator, the participant is willing and able to attend study visits, comply with the study procedures as specified in the protocol, and comply with the administration of the study drug.
Exclusion Criteria:
• Prior treatment with HLX-1502 for a PN.
• The participant has used any of the following systemic medications/ therapies within the specified period prior to enrollment: MEK-inhibitors, other drugs in the TKI class, HLX-1502, Participants may have received treatment for a PN or other tumor/malignancy but must have fully recovered to baseline or CTCAE ≤ Grade 1 from acute toxicities from prior therapies except alopecia, Myelosuppressive chemotherapy, Hematopoietic growth factors, Biologic (anti-neoplastic agent), Investigational Drugs, Any other systemically administered anti-neoplastic agent and Radiation therapy.
• Evidence of an NF1-related tumor such as optic pathway or other low-grade glioma, high-grade glioma, malignant peripheral nerve sheath tumor, or other cancer/tumor requiring treatment with chemotherapy, biologic therapy, surgery or radiation therapy.
• Participants with high-grade glioma, malignant peripheral nerve sheath tumor, or other malignancy who received treatment in the last 12 months. Exceptions include basal cell carcinoma of the skin and squamous cell carcinoma of the skin that have undergone potentially curative therapy. If the investigator has any clinical concerns for ANNUBP/Atypical Neurofibroma or MPNST, a biopsy sample must be taken prior to study confirming eligibility.
• Dental braces or prosthesis that interfere with volumetric analysis of the neurofibroma(s).
• Surgery: Any major surgery within 12 weeks before starting the Treatment Period or foreseen during participation in the trial, any minor surgeries within 1 month before first dose of study treatment and Participants must have complete wound healing from major surgery or minor surgery before the first dose of study treatment. Participants with clinically relevant ongoing complications from prior surgery are not eligible.
• Cataracts noted on ophthalmologic exam.
• Cardiovascular disorders.
• Other clinically significant disorders that would preclude safe study participation, including active infection, a known history of HIV seropositivity or known immunodeficiency or Known history of Hepatitis B or Hepatitis C.
• Participants who require treatment with a drug that is a substrate of CYP1A2, CYP2C8, UGT1A1, UGT1A3 with a narrow therapeutic index during protocol therapy.
• Known severe sensitivity to HLX-1502 or any excipient of HLX-1502 or history of allergic reactions attributed to compounds of similar chemical or biologic composition to HLX-1502.
• Known severe sensitivity to FD\&C Yellow No. 5.
• Participants receiving therapeutic anticoagulation with vitamin K antagonist.
• Participants presently with iron deficiency and/or actively receiving iron replacement or requiring treatment with copper or zinc for any indication at study baseline.
• Pregnant or breast-feeding women.
• Unable or unwilling to swallow tablets.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter ingestion and/or the absorption of HLX-1502.
• Participants who have other medical, social or concurrent challenges that are likely to negatively impact their ability to meet all of the trial obligations and therefore may increase the risk of safe participation in the study.
DRUG: HLX-1502
Neurofibromatosis Type 1
Neurofibromatosis Type 1, Plexiform Neurofibroma, pediatric
Regulating Together in Tuberous Sclerosis Complex (RT)
Molly Griffith - molly.griffith@cchmc.org
ALL
8 years to 17 years old
NA
NCT06105736
Inclusion Criteria:
* Children ages 8-17 years inclusive with a documented clinical and/or genetic diagnosis of TSC and exhibiting symptoms of behavioral dysregulation (identified on the TAND Checklist having temper tantrums, aggressive outbursts, self-injury, and/or impulsivity) are eligible for inclusion.
Additional inclusion/eligibility criteria include:
* Participants and their caregivers have access to a computer, phone, or tablet with video capability and stable internet connection. If lack of a device or internet service is the sole barrier to eligibility/participation, interested individuals will be connected to a TSC Clinic social worker to link them to existing government and charity programs specifically addressing this disparity in underserved communities and households in need (e.g., the Affordable Connectivity Program).
* Participants must also be willing to participate in treatment sessions and have minimal levels of functional verbal communication (child and their caregiver must be fluent in English
* Child must have a minimum IQ\>65 on the WASI-II at the screening/baseline visit).
Exclusion Criteria:
* Participants be on a stable medication regimen at least 4 weeks prior to enrollment
* Do not have a plan to start a new psychosocial intervention (e.g., individual psychotherapy, family psychotherapy, group psychotherapy or social skills training) or behavior medication within 30 days prior to enrollment or at any point during the study. ----Participants with significant disruptive, aggressive, self-injurious or sexually inappropriate behaviors deemed potentially dangerous or overly disruptive to the group dynamic/session, having significant co-occurring neuropsychiatric illness warranting other treatment approaches as determined by study clinician (e.g., substance use disorders, psychotic disorders, schizophrenia), or having significant sensory impairment that would limit participation in intervention curriculum/materials (e.g., blindness or uncorrected hearing loss) also will be excluded. BEHAVIORAL: Behavioral Intervention in a small group platform
TSC, Behavioral Symptoms
Liraglutide Treatment in Patients With Maturity-onset Diabetes of the Young (MODY)
Lily Deng - lily.deng@cchmc.org
ALL
10 years and over
PHASE2
NCT07029009
Inclusion Criteria:
* Diagnosis of MODY via genetic testing
* HgbA1c \>6.5%
Exclusion Criteria:
* History of anaphylaxis to GLP-1 receptor agonists
* Already taking GLP-1 receptor agonists
* on medications within the stimulant class
* have had bariatric surgery
* personal or family history of cancer, especially medullary thyroid cancer
* personal history of pancreatitis or pathogenic variants associated with increased risk of pancreatitis
* known active kidney disease
* severe hypoglycemia (glucose \< 50 mg/dL) within 3 months of study enrollment
* HbA1c \> 10.0%
* episode of diabetic ketoacidosis (DKA) in the past 3 months
* are currently pregnant
* BMI \< 18.5 kg/m2 and pediatric patients with BMI \< 5th percentile DRUG: Liraglutide
Maturity Onset Diabetes of the Young
Generic Database of Very Low Birth Weight Infants (GDB)
Brenda Poindexter - brenda.poindexter@cchmc.org
ALL
Up to 0 month(s) old
NCT00063063
Inclusion Criteria:
* Infants inborn at NICHD NRN centers that are:
* 401-1000 grams birth weight, and/or
* 20 0/7 to 28 6/7 weeks (\<29 weeks) gestational age
* Infants enrolled in one or more additional NICHD NRN interventional trials or time-limited observational studies. For infants that do not meet the inclusion criteria above, inclusion and exclusion criteria for the Generic Database are determined by the criteria for the additional trial(s). In these cases, infants that are larger than 1,000 grams and/or older than 29 weeks may be included in the GDB.
Exclusion Criteria:
* Infants \>1,000 grams birth weight and/or \>29 weeks gestational age
Note: These inclusion criteria were changed as of 1/1/2008. Prior to this date, all infants with birth weights between 401 and 1500 grams who are admitted to NRN NICUs within 14 days of birth were included in the database. OTHER: No Intervention
Infant, Newborn, Infant, Low Birth Weight, Infant, Small for Gestational Age, Infant, Premature
NICHD Neonatal Research Network, Extremely Low Birth Weight (ELBW), Prematurity
Child and Adolescent Registry for Participants With Narcolepsy
Melodie Boh - melodie.boh@cchmc.org
ALL
Up to 17 years old
NCT04899947
Inclusion Criteria:
* Any child or adolescent with a physician-confirmed diagnosis of narcolepsy
* Age less than 18 years
* Willing to participate in the Registry and complete the informed consent form
* Able to participate in English based registry
Exclusion Criteria:
* Age 18 years or more
* Fail to complete the informed consent form Narcolepsy
Improving Academic and Social Functioning in Middle-Schoolers With Autism
Ellie Thoma - skillsbuilder@cchmc.org
ALL
10 years to 15 years old
NA
NCT06705907
Inclusion Criteria:
* Diagnosis of autism
* No intellectual disability
* Problems with organization, materials management, and planning and prioritization
* Problems with social skills
* Fully included in middle school
* Stable medication and behavioral treatment regime
Exclusion Criteria:
* Home schooled
* Severe co-occurring psychopathology (e.g., aggression, suicidal)
* Non English-speaking BEHAVIORAL: Achieving Independence and Mastery in School (AIMS), BEHAVIORAL: Building Essential Social Skills for Teens (BESST)
Autism, Autism Spectrum Disorder
social skills, executive functions, academic achievement, middle school
Study of Talazoparib in Combination With Chemotherapy in Relapsed Pediatric AML to Determine Safety and Efficacy (PARPAML)
- cancer@cchmc.org
ALL
Up to 21 years old
PHASE1
NCT05101551
Inclusion Criteria:
• Aged ≤ 21 years.
• Acute myeloid leukemia (AML) OR acute leukemia of ambiguous lineage (acute undifferentiated leukemia or mixed phenotype acute leukemia), specified as either refractory (persistent leukemia after at least 2 courses of induction chemotherapy) or relapsed, and further defined as any one of the criteria below:
• Bone marrow specimen ≥ 5% leukemic blasts by flow, as assessed by Hematologics Inc.
• A single bone marrow specimen with at least 2 tests demonstrates ≥ 1% leukemic blasts by flow cytometry (as assessed by Hematologics Inc), AND at least one of the following: * Karyotypic abnormality with at least 1 metaphase similar or identical to diagnosis * FISH abnormality identical to one present at diagnosis * PCR or NGS-based demonstration of leukemogenic lesion identical to diagnosis
• Rising MRD \> 0.1% by flow cytometry on ≥ 2 serial samples, as assessed by Hematologics Inc.
• If an adequate bone marrow sample is not obtained, subjects may be enrolled if there is unequivocal evidence of leukemia based on ≥ 5% blasts in the peripheral blood
• \> 60 days has passed since hematopoietic stem cell transplant.
• Patients who have undergone previous allogeneic stem cell transplantation who are otherwise eligible must also be without evidence of any active graft versus host disease (GVHD), and off calcineurin inhibitors for at least 28 days (four weeks) prior to therapy. A physiologic dose of prednisone up to 3 mg/m2 (and a maximum of 7.5 mg) or equivalent other steroid dose is allowable.
• A minimum of 14 days has passed since completion of myelosuppressive therapy or gemtuzumab ozogamicin and all nonhematologic toxicities have resolved to Grade 0 or 1.
• A minimum of 24 hours has elapsed since the patient has completed any low-dose or non-myelosuppressive therapy (e.g., hydroxyurea or low-dose cytarabine (up to 100 mg/m2).
• Lansky (subjects ≤ 16 years old) or Karnofsky (subjects \> 16 years old) score ≥ 50.
• WBC ≤ 50,000/uL. This may be achieved using cytoreductive therapy such as hydroxyurea or low-dose cytarabine (up to 100 mg/m2/dose)
• Total bilirubin ≤ 2.0 x institutional upper limit of normal (ULN) for age.
• AST/ALT ≤ 5 x ULN for age
• Left ventricular ejection fraction ≥ 40% or ECHO shortening fraction ≥ 25%.
• Estimated serum creatinine ≥ 60 mL/min/1.73m2
Exclusion Criteria:
• Patients receiving or planning to receive ANY concurrent cancer therapy, including chemotherapy, radiation therapy, immunotherapy or biologic therapy.
• Patients with down syndrome.
• Patients with Acute Promyelocytic leukemia (APL) or Juvenile Myelomonocytic Leukemia (JMML).
• Patients with Bone Marrow Failure Syndrome.
• Pregnant subjects or those unwilling to use an effective method of birth control.
• Female subjects with infants who do NOT agree to abstain from breastfeeding.
• Inability or unwillingness of legal guardian/representative to give written informed consent.
• Patients with uncontrolled systemic fungal, bacterial, viral or other infection.
DRUG: Talazoparib, DRUG: Topotecan, DRUG: Gemcitabine
Acute Myeloid Leukemia
PARP Inhibitor
National Collaborative to Improve Care of Children With Complex Congenital Heart Disease (NPC-QIC)
Mark Timbers - mark.timbers@cchmc.org
ALL
Up to 15 month(s) old
NCT02852031
Inclusion Criteria:
* Fetuses or newborns diagnosed with HLHS or other univentricular condition
* Intended to undergo Norwood procedure
Exclusion Criteria:
* None OTHER: Collaborative Learning Network
Hypoplastic Left Heart Syndrome (HLHS)
A Prospective Database of Infants With Cholestasis (PROBE)
Jennifer Hawkins - jennifer.hawkins@cchmc.org
ALL
Up to 6 month(s) old
NCT00061828
INCLUSION CRITERIA
* Infant's age less than or equal to 180 days at initial presentation at the ChiLDReN clinical site.
* Diagnosis of cholestasis defined by serum direct or conjugated bilirubin greater than or equal to 2 mg/dl and suspected biliary atresia.
* The subject's parent(s)/guardian(s) willing to provide informed written consent.
EXCLUSION CRITERIA
* Acute liver failure.
* Previous hepatobiliary surgery with dissection or excision of biliary tissue.
* Diagnoses of bacterial or fungal sepsis (except where associated with metabolic liver disease)
* Diagnoses of hypoxia, shock or ischemic hepatopathy within the past two weeks (If the cholestasis persists beyond two weeks of the initiating event, the infant can be enrolled).
* Diagnosis of any malignancy.
* Presence of any primary hemolytic disease (except when diagnosed with biliary atresia or another cholestatic disease being studied by ChiLDREN).
* Diagnosis of any drug or Total parenteral nutrition (TPN)-associated cholestasis (except when diagnosed with biliary atresia or another cholestatic disease being studied by ChiLDREN).
* Diagnosis with Extracorporeal membrane oxygenation (ECMO)-associated cholestasis.
* Birth weight less than 1500g (except when diagnosed with biliary atresia).
Biliary Atresia
Rett Syndrome Registry (RSR)
Andrea Gonnella - Andrea.Gonnella@cchmc.org
ALL
0 years to 99 years old
NCT05432349
Inclusion Criteria:
* Male or female with a pathologic loss of function alteration of MECP2
Exclusion Criteria:
* Male or female with a gain of function alteration of MECP2, including those with MEPC2 duplication or triplication Rett Syndrome, Rett Syndrome, Atypical, Genetic Disease, Genetic Diseases, X-Linked, Intellectual Disability, Neurobehavioral Manifestations, Neurologic Manifestations, Neurologic Disorder, Neurodevelopmental Disorders, Nervous System Diseases
Rett syndrome, MECP2, Neurodevelopmental disorder, Registry, Natural History Study
SPEARHEAD-3 Pediatric Study
- cancer@cchmc.org
ALL
2 years to 21 years old
PHASE1
NCT05642455
Inclusion Criteria:
* Subject has histologically confirmed diagnosis of any one of the following cancers: (A) Synovial Sarcoma (SS), (B) MPNST, (C) Neuroblastoma, or (D) Osteosarcoma (OS).
* Age:
(A) Synovial Sarcoma: 2 to 17 years (B) MPNST, Neuroblastoma and Osteosarcoma: 2 to 21 years
* Body weight ≥ 10 kg
* Must have previously received a systemic chemotherapy
* Measurable disease prior to lymphodepletion according to RECIST v1.1 (or INCR, 2017 Neuroblastoma only).
* HLA-A\*02 positive
* Tumor shows MAGE-A4 expression confirmed by central laboratory.
* Performance Status:
(A) Subjects ≥16: Eastern Cooperative Oncology Group (ECOG) 0 or 1 (B) Subjects 2 to 16: Lansky score ≥ 80
• Subject has anticipated life expectancy of greater than 3 months in the opinion of the investigator.
Exclusion Criteria:
* Positive for HLA-A\*02:05 in either allele; or any A\*02 having same protein sequence as HLA-A\*02:05
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide.
* History of autoimmune or immune mediated disease
* Known central nervous system (CNS) metastases.
* Other prior malignancy that is not considered by the Investigator to be in complete remission
* Clinically significant cardiovascular disease
* Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus
* Pregnant or breastfeeding
* Experiencing ongoing rapid disease progression that in the opinion of the Investigator significantly increases the subjects risk associated with treatment. GENETIC: Afamitresgene autoleucel
Synovial Sarcoma, Malignant Peripheral Nerve Sheath Tumor (MPNST), Neuroblastoma (NBL), Osteosarcoma
Prospective Research Rare Kidney Stones (ProRKS) (ProRKS)
Prasad Devarajan - prasad.devarajan@cchmc.org
ALL
NCT02780297
Inclusion Criteria:
• Diagnosis of primary hyperoxaluria
• Diagnosis of enteric hyperoxaluria
• Diagnosis of Dent Disease
• Diagnosis of Cystinuria
• Diagnosis of adenine phosphoribosyltransferase deficiency (APRTd)
• Diagnosis of Lowe Syndrome
• Diagnosis of Dent Disease Carrier
Exclusion Criteria:
• Prior renal failure
• History of liver and/or kidney transplant.
Hyperoxaluria, Cystinuria, Dent Disease, Lowe Syndrome, Adenine Phosphoribosyltransferase Deficiency
primary hyperoxaluria, Dent Disease, enteric hyperoxaluria, cystinuria, Lowe Syndrome, Adenine phosphoribosyltransferase deficiency, PH, APRTd, APRT, hyperoxaluria, oxalate, oxalosis, PH type 1, PH type 2, PH type 3, Dents, Dent, Dent 1, Dent 2, APRT deficiency
18F-Fibroblast Activation Protein Inhibitor (18F-FAPI-74) in Tuberculosis Patients
Kerrigan Perkins - kerrigan.perkins@cchmc.org
ALL
18 years and over
NCT07077213
Inclusion criteria: Patients may be enrolled into this protocol only if all the following inclusion criteria are met:
* Greater than or equal to 18 years of age
* Culture confirmation of M. tuberculosis, or sputum positive by molecular testing (GeneXpert).
* Imaging evidence of suspected M. tuberculosis disease involving lung, and possible additional other sites of involvement. Modalities can include any imaging modality such as chest x-ray, CT, ultrasound, MRI, 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (\[18F\]FDG) PET/CT, bone scan.
* TB treatment initiation within 6-weeks by the time of the study PET/CT scan OR within 6-weeks after receiving 6-months of TB treatments. Using this approach, we will be able to assess fibrosis in TB patients at treatment initiation as well as having received TB treatments. The same patient may be re-consented for a scan at the later time-point.
* Subject is willing to give written informed consent.
* Subject is willing and able to comply with the protocol for the duration of the study including undergoing scheduled visits and study procedures.
* Screening clinical laboratory values must be within normal limits or judged not clinically significant by the investigator.
* Women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the radiotracer administration.
* Patients or their legal representatives must have the ability to read, understand and provide written informed consent for the initiation of any study related procedures.
Exclusion criteria: Patients will be excluded from enrollment if any of the following apply:
* Inadequate venous access (two antecubital or equivalent venous access sites are required for study drug injection and pharmacokinetics (PK) blood sampling, respectively)
* Lactating females
* Administered a radioisotope within 5 physical half-lives as part of a research study prior to study enrollment.
* Determined to have prior (external) radiation exposure from research studies which will exceed Radioactive Drug Research Committee (RDRC) annual radiation exposure limit of 5 rems.
* Any medical condition that in the judgment of the investigator would make the patient inappropriate for entry into this study.
COMBINATION_PRODUCT: 18F-FAPI-74
Tuberculosis, Pulmonary
Supraspinal Processing of Sensory Aspects of Pain (SCP)
Catherine Jackson - catherine.jackson@cchmc.org
ALL
10 years to 17 years old
NA
NCT05814497
Inclusion Criteria:
* Patients will need a diagnosis of a chronic pain derived congruent with ICD-11 criteria related to headache (migraine, daily headache), abdominal (FAPD), localized MSK (single limb/joint, low back or chest pain), diffuse MSK (widespread MSK pain), or CRPS
* If on medications, they need to be on stable doses of prescribed pain and/or psychiatric medications for 4 weeks before the baseline study visit.
* Male or female, age 10 -17 (inclusive)
* English speaking, able to complete interviews and questionnaires in English
Exclusion Criteria:
* Weight/size incompatible with MRI scanner
* Orthodontic braces, metallic or electronic implants, or other metal objects in the body which obscure or interfere with the MRI, or pose a risk from heating, movement, or malfunction in the MRI environment
* Claustrophobia
* Youth who are pregnant
* Any comorbid rheumatic disease, diagnosis of epilepsy, other neurological diseases, or medical condition (e.g. diabetes, cancer, IBD)
* Present psychiatric disease as defined by DSM IV (e.g. psychosis, bipolar disorder, major depression, generalized anxiety disorder), alcohol or drug dependence, or documented developmental delays or impairments (e.g., autism, cerebral palsy, ADHD, or mental retardation) that, in the opinion of the investigator, would interfere with adherence to study requirements or safe participation in the study
* Skin conditions or past skin damage on the arms or legs in or near sites of sensory testing
* Outside the age range (9 years old or younger; 18 years or older) at the time of consent
* History of \> 1 month opioid treatment. OTHER: Multisensory Task, OTHER: Graphesthesia, OTHER: Divided attention
Migraine in Children, Complex Regional Pain Syndromes, Musculoskeletal Pain, Functional Abdominal Pain Syndrome, Fibromyalgia
chronic pain
Gene Therapy Trial for Otoferlin Gene-mediated Hearing Loss
Sawvell Katie - katie.sawvell@cchmc.org
ALL
PHASE3
NCT05821959
Criteria for Inclusion:
• Participants may be of any age, based on Cohort Criteria
• At least two mutations in the otoferlin gene
• Clinical presentation of Profound (Part A) or Severe to Profound (Parts B, C, and D) bilateral sensorineural hearing loss as assessed by ABR
• Preserved distortion product otoacoustic emissions (DPOAEs)
• Able and willing to comply with all study requirements, including willingness to participate in a separate long term follow-up study after completion of this trial Criteria for Exclusion:
• Persistent ear infections, anatomic or other abnormalities of the ear, and/or medical conditions that would contraindicate undergoing surgery, anesthesia, and/or administration of investigational gene therapy
• Cochlear Implant(s) in the ear(s) to receive AAVAnc80-hOTOF
• Prior participation in a clinical trial with an investigational drug, within six months prior to administration, or any prior participation in a gene therapy clinical trial (with the exception of AK-OTOF-101 for Part D participants)
• Participants may be of any age, based on Cohort Criteria
• At least two mutations in the otoferlin gene
• Clinical presentation of Profound (Part A) or Severe to Profound (Parts B, C, and D) bilateral sensorineural hearing loss as assessed by ABR
• Preserved distortion product otoacoustic emissions (DPOAEs)
• Able and willing to comply with all study requirements, including willingness to participate in a separate long term follow-up study after completion of this trial Criteria for Exclusion:
• Persistent ear infections, anatomic or other abnormalities of the ear, and/or medical conditions that would contraindicate undergoing surgery, anesthesia, and/or administration of investigational gene therapy
• Cochlear Implant(s) in the ear(s) to receive AAVAnc80-hOTOF
• Prior participation in a clinical trial with an investigational drug, within six months prior to administration, or any prior participation in a gene therapy clinical trial (with the exception of AK-OTOF-101 for Part D participants)
COMBINATION_PRODUCT: AAVAnc80-hOTOF via Akouos Delivery Device, COMBINATION_PRODUCT: AAVAnc80-hOTOF via Akouos Delivery Device and Precision Delivery Mechanism
Sensorineural Hearing Loss, Bilateral
Otoferlin, Auditory neuropathy (AN), Deafness, autosomal recessive 9 (DFNB9), Hearing loss, Hearing loss, bilateral, Hearing loss, sensorineural