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A Study to See if Tolvaptan is Safe in Infants and Children Who at Enrollment Are 28 Days to Less Than 18 Years Old With Autosomal Recessive Polycystic Kidney Disease (ARPKD)
Kelli Krallman - Kelli.Krallman@cchmc.org
ALL
28 days to 18 years old
PHASE3
NCT04782258
Inclusion Criteria:
• Male or female subjects between 28 days and less than 18 years of age, with clinical features that are consistent with a diagnosis of ARPKD.
• Ability for parent/legal guardian to provide written, informed consent prior to initiation of any trial-related procedures, and ability, in the opinion of the principal investigator, to comply with all the requirements of the trial. Ability to provide written informed assent from all subjects old enough per local laws to provide assent.
Exclusion Criteria:
• Premature birth (≤ 32 weeks gestational age) for infants 28 days to \< 12 weeks of age.
• Anuria or RRT defined as intermittent or continuous hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration or history of kidney transplantation.
• Evidence of syndromic conditions associated with renal cysts (other than ARPKD).
• Abnormal liver function tests including ALT and AST, \> 1.2 × ULN (upper limit of normal).
• Has splenomegaly or portal hypertension (HTN).
• Parents with renal cystic disease.
• Receiving chronic diuretic that could not be adjusted after tolvaptan initiation.
• Cannot be monitored for fluid balance.
• Has or at risk of having sodium and potassium electrolyte imbalances, as determined by the investigator.
• Has or at risk of having significant hypovolemia as determined by investigator.
• Clinically significant anemia, as determined by investigator.
• Platelets \< 50000 µL.
• Severe systolic dysfunction defined as ejection fraction \< 14%.
• Serum sodium levels \< 130 mmol/L or \>145 mmol/L.
• Taking any other experimental medications.
• Require ventilator support.
• Taking medications known to induce CYP3A4 (CYP = Cytochrome P).
• Having an infection including viral that would require therapy disruptive to IMP (Investigational Medicinal Product) dosing.
• Females who are breast-feeding or who have a positive pregnancy test result prior to receiving IMP.
• Subjects with a history of substance abuse (within the last 6 months).
• Subjects who have bladder dysfunction and/or difficulty voiding.
• Subjects taking a vasopressin agonist (eg, desmopressin).
• Subjects with a history of persistent noncompliance with antihypertensive or other important medical therapy.
• Subjects taking medications or having concomitant illnesses likely to confound endpoint assessments, including taking approved (ie, marketed) therapies for the purpose of affecting PKD cysts such as tolvaptan, vasopressin antagonists, anti-sense ribonucleic acid (RNA) therapies, rapamycin, sirolimus, everolimus, or somatostatin analogs (ie, octreotide, sandostatin).
• Received or are scheduled to receive a liver transplant.
• History of cholangitis within the last 6 months.
• Has findings consistent with clinically significant portal hypertension (eg, varices, variceal bleeding, hypersplenism indicated by thrombocytopenia).
• Subjects who do not agree to remain abstinent or assent to use a combination of 2 of the following highly effective birth control methods for at least 28 days before the first dose of IMP, during the trial (including during IMP dose interruptions), and for at least 30 days after the last dose of IMP: * Barrier method of contraception: condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide * Intrauterine device * Hormone-based contraceptives which are associated with inhibition of ovulation.
DRUG: Tolvaptan Suspension, DRUG: Tolvaptan Tablets
Autosomal Recessive Polycystic Kidney (ARPKD)
ARPKD, TOLVAPTAN, Polycystic Kidney Disease, Autosomal Recessive Polycystic Kidney Disease, Adolescent, Renal Cysts, Oligohydramnios, Anhydramnios
Follow-up Automatically vs. As-Needed Comparison (FAAN-C) Trial (FAAN-C)
Holly Flake - Holly.Flake@cchmc.org
ALL
Up to 18 years old
NA
NCT05471908
Inclusion Criteria:
* Age \<18 years at the time of randomization
* Hospitalization due to a primary diagnosis of pneumonia, skin and soft tissue infection, acute gastroenteritis, or urinary tract infection.
* Parent speaks English or Spanish.
Exclusion Criteria:
* Presence of a comorbid disease that is both chronic and complex
* Principal disease required surgical intervention (beyond superficial incision and drainage)
* Immunodeficiency
* A well-child check-up or post-hospitalization follow-up visit is already scheduled within 7 days of hospital discharge
* Parent or participant strongly prefers PRN or automatic follow-up
* A medical provider feels strongly that a post-hospitalization follow-up visit is needed within 7 days of hospital discharge
* Sibling concurrently hospitalized
* Unable to identify a clinic where the participant would receive any needed post-hospitalization follow-up
* Diagnosis of pneumonia complicated by:
o Receiving a chest tube
* Diagnosis of urinary tract infection complicated by:
* History of neurogenic bladder or urologic surgery
* Renal imaging anticipated within 7 days of hospital discharge
* Renal abscess
* Diagnosis of skin and soft tissue infection complicated by:
* Chronic wound
* Postoperative infection
* Predisposition to poor wound healing
* Discharging with a drain in place
* Complicated by necrotizing fasciitis or toxic shock syndrome
* Diagnosis of gastroenteritis complicated by:
* Hemolytic uremic syndrome BEHAVIORAL: As-needed follow up, BEHAVIORAL: Automatic follow-up
Pneumonia, Urinary Tract Infections, Soft Tissue Infections, Gastroenteritis
post-hospitalization, follow-up care, patient centered care, randomized control trial
A Global Prospective Observational Registry of Patients With Pompe Disease
Jenel Facey - jenel.facey@cchmc.org
ALL
NCT06121011
Inclusion Criteria:
* Diagnosis of LOPD or IOPD based on documented deficiency of GAA enzyme activity and/or GAA genotyping
Exclusion Criteria:
* Patients who are currently receiving investigational therapy for Pompe disease in a clinical trial, a compassionate use program, or an expanded access program (EAP) BIOLOGICAL: Cipaglucosidase alfa, DRUG: Miglustat, BIOLOGICAL: Alglucosidase alfa or Avalglucosidase alfa, OTHER: Untreated
Pompe Disease
A Gaucher Disease Gene Therapy Trial With FLT201 (GALILEO-3)
Laurie Bailey - laurie.bailey@cchmc.org
ALL
18 years and over
PHASE3
NCT07223944
Key
Inclusion Criteria:
* Aged ≥18 years at time of screening.
* Clinical diagnosis of Gaucher disease type 1
* Stable hemoglobin concentration at baseline
* Stable platelet count at baseline
* Receiving ERT or SRT without interruption for at least 2 years
Key Exclusion Criteria:
* Diagnosed or suspected Gaucher disease type 2 or type 3
* Positive for AAVS3 neutralizing antibodies.
* Abnormal lab values, conditions or diseases that would make the participant unsuitable for the study
* Positive pregnancy test or lactating
* History of hematopoietic stem cell transplant (HSCT)/bone marrow transplant or any solid organ transplant.
* History of receiving any gene therapy or cell therapy.
* History of total splenectomy. Note: Additional protocol defined Inclusion and Exclusion criteria apply GENETIC: FLT201
Gaucher Disease Type 1
Project: Every Child for Younger Patients With Cancer
- cancer@cchmc.org
ALL
Up to 25 years old
NCT02402244
Inclusion Criteria:
* Enrollment must occur within 6 months of initial disease presentation OR within 6 months of refractory disease, disease progression, disease recurrence, second or secondary malignancy, or post-mortem
* Patients previously enrolled on ACCRN07 are eligible to enroll on Tracking Outcome, Registry and Future Contact components of APEC14B1 any time after they reach age of majority
* Patients with a known or suspected neoplasm that occurs in the pediatric, adolescent or young adult populations are eligible for enrollment as follows:
* All cancer cases with an International Classification of Diseases for Oncology (ICD-O) histologic behavior code of one "1" (borderline), two "2" (carcinoma in situ) or three "3" (malignant)
* All neoplastic lesions of the central nervous system regardless of behavior, i.e., benign, borderline or malignant
* All neoplastic lesions of the kidney regardless of behavior, i.e., benign, borderline or malignant
* The following other benign/borderline conditions:
* Mesoblastic nephroma
* Teratomas (mature and immature types)
* Myeloproliferative diseases including transient myeloproliferative disease
* Langerhans cell histiocytosis
* Lymphoproliferative diseases
* Desmoid tumors
* Gonadal stromal cell tumors
* Neuroendocrine tumors including pheochromocytoma
* Melanocytic tumors, except clearly benign nevi
* Ganglioneuromas
* Subjects must be =\< 25 years of age at time of original diagnosis, except for patients who are being screened specifically for eligibility onto a COG (or COG participating National Clinical Trials Network \[NCTN\]) therapeutic study, for which there is a higher upper age limit
* All patients or their parents or legally authorized representatives must sign a written informed consent and agree to participate in at least one component of the study; parents will be asked to sign a separate consent for their own biospecimen submission
* If patients or their parents or legally authorized representatives have not signed the Part A subject consent form at the time of a diagnostic bone marrow procedure, it is recommended that they initially provide consent for drawing extra bone marrow using the Consent for Collection of Additional Bone Marrow; consent using the Part A subject consent form must be provided prior to any other procedures for eligibility screening or banking under APEC14B1 OTHER: Cytology Specimen Collection Procedure, OTHER: Medical Chart Review
Adrenal Gland Pheochromocytoma, Carcinoma In Situ, Central Nervous System Neoplasm, Childhood Immature Teratoma, Childhood Kidney Neoplasm, Childhood Langerhans Cell Histiocytosis, Childhood Mature Teratoma, Congenital Mesoblastic Nephroma, Desmoid Fibromatosis, Ganglioneuroma, Lymphoproliferative Disorder, Malignant Neoplasm, Malignant Solid Neoplasm, Melanocytic Neoplasm, Myeloproliferative Neoplasm, Neoplasm of Uncertain Malignant Potential, Neuroendocrine Neoplasm, Stromal Neoplasm
Registry for Stage 2 Type 1 Diabetes
Cierra Farrell - cierra.farrell@cchmc.org
ALL
NCT06481904
Inclusion Criteria:
TZIELD-Exposed Cohort
* Patients in the US diagnosed with Stage 2 T1D who are planned to initiate TZIELD treatment according to the currently approved label or who have initiated TZIELD treatment within 6 months prior to enrollment:
* Day 1: 65 mcg/m2
* Day 2: 125 mcg/m2
* Day 3: 250 mcg/m2
* Day 4: 500 mcg/m2
* Days 5 through 14: 1,030 mcg/m2 per day
* Cumulative dose is approximately 11,240 mcg/m2
* Appropriate written informed consent/assent as applicable for the age of the patient
TZIELD-Unexposed Cohort
* Patients in the US diagnosed with Stage 2 T1D but who are not treated with TZIELD
* Appropriate written informed consent/assent as applicable for the age of the patient
Exclusion Criteria:
* Patients who initiated TZIELD treatment more than 6 months prior to enrollment
* Patients who had participated in a previous clinical trial for TZIELD
* Patients in an ongoing clinical trial of an investigational product or who had ended participation within 6 months prior to study enrollment; patients participating in other observational studies may be enrolled
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. DRUG: TZIELD (teplizumab-mzwv)
Type 1 Diabetes
BSGM to Evaluate Patients With GI Symptoms
Khalil El-Chammas, MD - Khalil.El-Chammas@cchmc.org
ALL
8 years to 25 years old
NCT05880199
Inclusion Criteria for Cases
• Males or females age 8 to 25 years.
• Females ≥11 years of age or who have reached menarche must have a negative urine pregnancy test.
• Confirmed diagnosis of a Functional Gastrointestinal and/or Motility Disorder OR undergoing one of the following procedures as part of their clinical care at one of the participating centers:
• HRVB
• PENFS
• ADM
• Colonic Manometry
• Pyloric Botox
• Pyloric Dilation
• Gastric Scintigraphy
• GES
• gammaCore
• Those with a body mass index of \< 35.
• Parental/guardian permission (informed consent) and if appropriate, child assent. Exclusion Criteria for Cases
• History of skin allergies or a history of extreme sensitivity to cosmetics or lotions. Currently open wounds, abrasions, infected or inflamed abdominal skin. (Please note, majority of feeding tubes can be accommodated by the array placement.)
• Pregnant women.
• Those with any condition, where fasting is not recommended by a physician.
• Any allergies to foods that may be present in the standardized meal that cannot be accommodated with an acceptable substitute meal.
• Those with physical limitations, who are not able to maintain a relaxed reclined position for the study visit duration.
• Those with major developmental delay or cognitive impairment, who are not able to report their symptoms/feelings in the questionnaires.
• Those with GI motility disorders that are limited in the esophagus, and the gastric mapping is restricted to capture relevant data based on the investigator's discretion.
• Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures. Inclusion Criteria for Controls
• Males or females age 8 to 25 years.
• Females ≥11 years of age or who have reached menarche must have a negative urine pregnancy test.
• Do not have an active Functional Gastrointestinal disorder (FGID) diagnosis and will not be undergoing any procedures outlined in the recruitment plan in the near future.
• Those with a body mass index of \< 35.
• Individuals may include siblings of those with FGIDs.
• Parental/guardian permission (informed consent) and if appropriate, child assent. Exclusion Criteria for Controls
• History of skin allergies or a history of extreme sensitivity to cosmetics or lotions. Currently open wounds, abrasions, infected or inflamed abdominal skin.
• Pregnant women.
• Those with any condition, where fasting is not recommended by a physician.
• Allergies to foods that may be included in the standardized meal that cannot be accommodated with an acceptable substitute meal.
• Those with physical limitations, who are not able to maintain a relaxed reclined position for the study duration.
• Those with major developmental delay or cognitive impairment, who are not able to report their symptoms/feelings in the questionnaires.
• Those with GI motility disorders that are limited in the esophagus, and the gastric mapping is restricted to capture relevant data based on the investigator's discretion.
• Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
• Males or females age 8 to 25 years.
• Females ≥11 years of age or who have reached menarche must have a negative urine pregnancy test.
• Confirmed diagnosis of a Functional Gastrointestinal and/or Motility Disorder OR undergoing one of the following procedures as part of their clinical care at one of the participating centers:
• HRVB
• PENFS
• ADM
• Colonic Manometry
• Pyloric Botox
• Pyloric Dilation
• Gastric Scintigraphy
• GES
• gammaCore
• Those with a body mass index of \< 35.
• Parental/guardian permission (informed consent) and if appropriate, child assent. Exclusion Criteria for Cases
• History of skin allergies or a history of extreme sensitivity to cosmetics or lotions. Currently open wounds, abrasions, infected or inflamed abdominal skin. (Please note, majority of feeding tubes can be accommodated by the array placement.)
• Pregnant women.
• Those with any condition, where fasting is not recommended by a physician.
• Any allergies to foods that may be present in the standardized meal that cannot be accommodated with an acceptable substitute meal.
• Those with physical limitations, who are not able to maintain a relaxed reclined position for the study visit duration.
• Those with major developmental delay or cognitive impairment, who are not able to report their symptoms/feelings in the questionnaires.
• Those with GI motility disorders that are limited in the esophagus, and the gastric mapping is restricted to capture relevant data based on the investigator's discretion.
• Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures. Inclusion Criteria for Controls
• Males or females age 8 to 25 years.
• Females ≥11 years of age or who have reached menarche must have a negative urine pregnancy test.
• Do not have an active Functional Gastrointestinal disorder (FGID) diagnosis and will not be undergoing any procedures outlined in the recruitment plan in the near future.
• Those with a body mass index of \< 35.
• Individuals may include siblings of those with FGIDs.
• Parental/guardian permission (informed consent) and if appropriate, child assent. Exclusion Criteria for Controls
• History of skin allergies or a history of extreme sensitivity to cosmetics or lotions. Currently open wounds, abrasions, infected or inflamed abdominal skin.
• Pregnant women.
• Those with any condition, where fasting is not recommended by a physician.
• Allergies to foods that may be included in the standardized meal that cannot be accommodated with an acceptable substitute meal.
• Those with physical limitations, who are not able to maintain a relaxed reclined position for the study duration.
• Those with major developmental delay or cognitive impairment, who are not able to report their symptoms/feelings in the questionnaires.
• Those with GI motility disorders that are limited in the esophagus, and the gastric mapping is restricted to capture relevant data based on the investigator's discretion.
• Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
DEVICE: Body surface gastric mapping device
Gastrointestinal Motility Disorders in Children, Functional Gastrointestinal Disorders, Gastroparesis, Dyspepsia and Other Specified Disorders of Function of Stomach
GI motility, gastroparesis, functional dyspepsia
A Pragmatic Clinical Trial of the WE BEAT Well-Being Education Program in Adolescent Congenital Heart Disease: WE BEAT CHD Study (PHN WBC)
Elise Pickering - Elise.Pickering@cchmc.org
ALL
12 years to 17 years old
NA
NCT07525843
Inclusion Criteria:
* Age 12-17 years old
* CHD of moderate or severe complexity (Class II/III, 2018 AHA/ACC ACHD, Table 4)
* English or Spanish language proficiency
* Receives cardiology care at a PHN or PHN auxiliary site
* Parent or guardian and participant willing to comply with protocol and provide written/electronic informed consent and assent
Exclusion Criteria:
* CHD of mild or simple complexity (Class I, 2018 AHA/ACC ACHD, Table 4)
* Prior heart transplant to treat CHD
* Heart disease that is not classified as structural CHD (e.g., connective tissue disease, genetic cardiomyopathy, or acquired heart disease)
* Cognitive or developmental conditions that limit program participation and/or ability to complete self-reported measures as determined by a primary cardiology clinician
* Suicidality, homicidality, or psychosis in the past 12 months as per medical chart review, clinician report, or eligibility screening
* Medically unable to participate (e.g., intubated, unable to respond verbally, active delirium) BEHAVIORAL: Telemedicine-based resiliency-building intervention
Patient-Reported Outcome Measures (PROMs), Pragmatic Trial, Adolescent Congenital Heart Disease, Resiliency-building Intervention, Resilience, Psychological, Telemedicine-Based Education
WE BEAT, Well-Being Education Program, Adolescent CHD, Pragmatic Clinical Trial, Telemedicine
Inspiring New Science In Guiding Healthcare in Turner Syndrome Registry (INSIGHTS)
Leah Tyzinksi - leah.tyzinski@cchmc.org
FEMALE
NCT05052606
Inclusion Criteria:
• Individuals with TS and TS variants as defined by the TS Clinical Practice Guideline definition (karyotype consistent with TS, phenotypic female, clinical feature(s) of TS)
• Informed consent/assent as appropriate
Exclusion Criteria:
a. Lack of a TS diagnosis on file OTHER: No intervention
Turner Syndrome
Standardizing Treatments for Pulmonary Exacerbations - Aminoglycoside Study (STOP360AG)
Kelly Thornton - Kelly.Thornton@cchmc.org
ALL
6 years and over
PHASE4
NCT05548283
Inclusion Criteria:
* All genders ≥ 6 years of age at Visit 1
* Documentation of a CF diagnosis
* Clinician intent to treat index CF PEx with a planned 14-day course of IV antimicrobials
* At least one documented Pa positive culture within two years prior to Visit 1
Exclusion Criteria:
* Participant is not pregnant
* No known renal impairment or history of solid organ transplantation
* No IV antimicrobial treatment, ICU admission, pneumothorax, or hemoptysis within 6 weeks prior to Visit 1
* No use of investigational therapies, new CF transmembrane conductance regulator (CFTR) modulators, or treatment for Nontuberculous mycobacteria (NTM) within 4 weeks prior to Visit 1
* No history of hypersensitivity, vestibular, or auditory toxicity with aminoglycosides
* No more than one day of IV aminoglycosides administered for the current PEx treatment prior to Visit 1 DRUG: Beta-lactam antibiotic, DRUG: Aminoglycoside
Cystic Fibrosis, Cystic Fibrosis Pulmonary Exacerbation
Cystic Fibrosis, CF, Cystic Fibrosis Pulmonary Exacerbation, aminoglycoside, beta-lactam, β-lactam, STOP, STOP360
Thoracotomy Versus Thoracoscopic Management of Pulmonary Metastases in Patients With Osteosarcoma
- cancer@cchmc.org
ALL
Up to 50 years old
PHASE3
NCT05235165
Inclusion Criteria:
* Patients must be \< 50 years at the time of enrollment.
* Patients must have =\< 4 nodules per lung consistent with or suspicious for metastases, with at least one of which being \>= 3 mm and all of which must be =\< 3 cm size.
* Note: Patient must have eligibility confirmed by rapid central imaging review.
* Lung nodules must be considered resectable by either open thoracotomy or thoracoscopic surgery. Determination of resectability is made by the institutional surgeon.
* Patients must have a histological diagnosis of osteosarcoma.
* Patients must have evidence of metastatic lung disease at the time of initial diagnosis, or at time of 1st recurrence following completion of therapy for initially localized disease.
* Patients with newly diagnosed disease must have completed successful gross tumor resection for their primary tumor or surgical local control of primary tumor must be planned to be performed simultaneously with thoracic surgery.
* Newly diagnosed patients must be receiving or recently completed (within 60 days) systemic therapy considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
* Patients at time of 1st recurrence must have completed systemic therapy for their initial primary tumor, considered by the treating physician to be standard treatment for newly diagnosed osteosarcoma (eg, cisplatin-doxorubicin or ifosfamide-based drug regimens) at the time of enrollment on this study. Dose and drug modifications for toxicity do not exclude patients from participation.
Exclusion Criteria:
* Patients with unresectable primary tumor.
* Patients with pulmonary metastatic lesions that would require anatomic resection (lobectomy or pneumonectomy) or lesions that are defined as "central" (i.e., central lesion involves or is proximal to segmental bronchi and peripheral is lesion distal to segmental bronchi).
* Patients with chest wall or mediastinal based metastatic lesions, or with significant pleural effusion.
* Patients with disease progression at either the primary or pulmonary metastatic site while on initial therapy. Note: Once the patient has been enrolled on the study, additional computed tomography (CT) scans are not anticipated prior to thoracic surgery. Note: Some variation in nodule size measurements over the course of pre-operative therapy is anticipated and does not qualify for exclusion unless deemed true disease progression by the primary treatment team.
* Patients with evidence of extrapulmonary metastatic disease.
* Patients who received therapeutic pulmonary surgery for lung metastasis prior to enrollment.
* 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: Computed Tomography, OTHER: Questionnaire Administration, PROCEDURE: Thoracoscopy, PROCEDURE: Thoracotomy
Metastatic Malignant Neoplasm in the Lung, Metastatic Osteosarcoma, Osteosarcoma
I-DECIDE After Bronchiolitis Hospitalization (I-DECIDE)
Ramya Ramya Adapa - RamyaSriLakshmi.Adapa@cchmc.org
ALL
0 months to 24 months old
NA
NCT07243652
Inclusion Criteria:
* Primary diagnosis of bronchiolitis, discharged by a generalist inpatient service from a non-ICU, non-emergency department, non-step down unit
Exclusion Criteria:
* Children with a history of gestational age \<28 weeks, chronic lung disease, complex or hemodynamically significant heart disease, immunodeficiency, or neuromuscular disease
* Children being discharged with home oxygen therapy OTHER: Moderate-Resource Implementation Strategy, OTHER: High-Resource Implementation Strategy
Bronchiolitis Acute
A Phase 1b, Open-Label Study of DISC-3405 in Participants With Sickle Cell Disease (SCD)
Kara McClure - kara.mcClure@cchmc.org
ALL
18 years and over
PHASE1
NCT07187973
Inclusion Criteria:
• Aged 18 years or older at the time of signing the informed consent form (ICF).
• Male or female study participants with SCD HbSC or HbSS.
• Participants who have been diagnosed with any of the following SCD-related complications: between 1-10 episodes of VOC in the past 12 months, any history of sickle cell related retinopathy, silent cerebral infarct, avascular necrosis, sensorineural hearing loss; or at least 1 episode of priapism, hepatic sequestration, splenic sequestration, or splenic infarct within the last 12 months as assessed locally.
• Hgb ≥7.0 g/dL during Screening. The first 2 participants must have an Hgb ≥9 g/dL.
• Normal alpha globin gene screen.
• Absolute reticulocyte count or % reticulocyte count \>1.5 × upper limit of normal (ULN) during Screening.
• TSAT ≥15% at Screening.
• Ferritin ≥50 ng/mL for HbSC or ≥100 ng/mL for HbSS (ferritin must be \<1000 ng/mL at Screening).
• For participants taking hydroxyurea, L-glutamine, or crizanlizumab, stable dose for at least 2 months prior to Screening and with no anticipated need for dose adjustments during the study.
• If male, not vasectomized for at least 6 months, with female sexual partner(s) of childbearing potential, agrees he and partner will use double methods of the following highly effective methods of birth control (described below) from the first dose of randomized study drug until 120 days after the last administration of study drug and must not donate sperm during their study participation:
• Stable hormonal contraceptive (≥3 months; female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Intrauterine device, in place for at least 3 months (female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Surgically sterile by hysterectomy, bilateral oophorectomy, or bilateral tubal ligation (female partner) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• If female, then EITHER postmenopausal, defined as at least 12 months natural, spontaneous amenorrhea, 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone (FSH) \>40 mIU/mL at Screening, or at least 6 weeks following surgical menopause (bilateral oophorectomy with or without hysterectomy); surgically sterile, OR agree to use 1 of the following highly effective methods of birth control on Day 1 (or earlier) and for at least 120 days after the last administration of study drug:
• Stable hormonal contraceptive (≥3 months) in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Intrauterine device, in place for at least 3 months in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Tubal ligation or single male partner with vasectomy in conjunction with a barrier method (eg, condom \[male or female\] or diaphragm).
• Negative pregnancy test (females of childbearing potential) prior to dosing.
• Able to understand the study aims, procedures, and requirements, and provide written informed consent.
• Able to comply with all study procedures.
Exclusion Criteria:
• Participants who are receiving regularly scheduled blood (RBC) transfusion therapy or phlebotomy or have received RBC transfusion or phlebotomy within 60 days of Screening.
• Hospitalized for VOC or other sickle cell related complication within 14 days of Screening.
• Participants with clinically significant bacterial, fungal, parasitic, or viral infection.
• Active HIV, hepatitis B, or C. A positive hepatitis or HIV result should be discussed between the Investigator and Sponsor prior to enrollment.
• Significant renal dysfunction, evidenced by estimated glomerular filtration rate of \<60 mL/min/1.73 m2 at the Screening visit, as assessed locally.
• Hepatic dysfunction characterized by alanine aminotransferase (ALT) \>2.5 × ULN.
• Any episode of ACS in the last 6 months.
• Prior or planned hematopoietic stem cell transplant or gene therapy.
• History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to Screening.
• History of invasive malignancies within the last 5 years, except localized cured prostate cancer and cervical cancer, or other malignancies deemed acceptable by the Sponsor.
• Major surgery within 8 weeks before Screening or incomplete recovery from any previous surgery.
• A history or known allergic reaction to any IP excipients or history of anaphylaxis to any food or drug.
• History of alcohol dependence or excessive alcohol consumption, as assessed by the Investigator.
• Other medical or psychiatric condition or laboratory finding not specifically noted above that, in the judgment of the Investigator or Sponsor, would put the participant at an unacceptable risk or otherwise preclude the participant from participating in the study.
• Condition or concomitant medication that would confound the ability to interpret clinical, clinical laboratory, including a major psychiatric condition that has had an exacerbation or required hospitalization in the last 6 months.
• If female, pregnant or breastfeeding.
• Participation in any other clinical protocol or investigational study that involves administration of experimental therapy and/or therapeutic devices within 30 days of Screening.
• Participants with a history of transient ischemic attack or stroke may be considered in consultation with Sponsor.
DRUG: DISC-3405
Sickle Cell Disease
Efficacy and Safety Study of Rimegepant for the Preventative Treatment of Migraine in Pediatric Subjects
Michelle Shin - michelle.shin@cchmc.org
ALL
6 years to 17 years old
PHASE3
NCT05156398
Inclusion Criteria:
• Subject has at least a 6 month history of migraine (with or without aura) and including the following:
• 14 or less headache days per month during the 3 month period prior to the Screening Visit
• 6 or more migraine days during the Observation Period
• 14 or less headache days during the Observation Period
• Pediatric Migraine Disability Assessment Scale (PedMIDAS) Disability Score of \>10 to ≤50, indicating mild (score of 11 to 30) or moderate (score of 31 to 50) disruption in daily activities, as assessed at the Baseline (Randomization) Visit
• Ability to verbally distinguish migraine attacks from tension/cluster or other types of headaches
• Migraine attacks, on average, lasting 4 - 72 hours if untreated
• Subjects on prophylactic migraine medication are permitted to remain on therapy if the dose has been stable for at least 3 months (12 weeks) prior to the Screening Phase, and the dose is not expected to change during the course of the study. 2) Male and female subjects ≥ 6 to \<18 years; subjects must be less than 18 at the time of signing assent / consent. 3)Subjects must have a weight of ≥40 kg (child cohort requirement ≥15 kg) at the Screening Visit.
Exclusion Criteria:
• Subjects with a history of basilar migraine, cluster headaches, or hemiplegic migraine
• The subject has a continuous migraine (defined as an unrelenting headache) within 1 month prior to Screening Visit.
• The subject has a history or diagnosis of complications of migraine
• The subject has a confounding and clinically significant pain syndrome that may interfere with the subject's ability to participate in this study.
• The subject has any current psychiatric condition that is uncontrolled and/or untreated for a minimum of 6 months prior to the Screening Visit. Subjects with a lifetime history of psychosis and/or mania are excluded.
• History of suicidal behavior or the subject is at risk of self-harm or harm to others.
• History of major psychiatric disorder.
• The subject has a current diagnosis or history of substance abuse
• The subject has a history of moderate or severe head trauma or other neurological disorder (including seizure disorder) or systemic medical disease that is, in the investigator's opinion, likely to affect central nervous system functioning.
DRUG: Rimegepant, DRUG: Placebo
Migraine
Migraine, Migraine prevention, Phonophobia, Photophobia, Nausea, Pediatric migraine, Adolescent migraine
Study to Evaluate Sotatercept (MK-7962) in Children With Pulmonary Arterial Hypertension (PAH) (MK-7962-008) (MOONBEAM)
Jaynee Bartsch - jaynee.bartsch@cchmc.org
ALL
1 year to 17 years old
PHASE2
NCT05587712
Inclusion Criteria
* Documented, historic diagnostic right heart catheterization (RHC) any time before Screening confirming the diagnosis of PAH WHO Group 1 in any of the following subtypes:
* Idiopathic pulmonary arterial hypertension (IPAH)
* Heritable PAH
* Drug/toxin-induced PAH
* PAH associated with connective tissue disease
* PAH-congenital heart disease (CHD) with shunt closure \>6 months before Screening and subsequently confirmed by RHC before Screening
* PAH with coincidental shunt.
* Must be on a stable dose(s) of background PAH therapy (phosphdiesterase-5 (PDE5) inhibitors, endothelin receptor antagonists (ERAs), soluble guanylate cyclase stimulators (sGCS), or prostanoids \[including subcutaneous and intravenous\])
* If male, agree to the following during the intervention period and for at least 16 weeks (112 days) after the last dose of study intervention:
* Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent or
* Uses contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
* Uses a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
* If female, must be either not a WOCBP or use a contraceptive method that is highly effective or be abstinent from heterosexual intercourse during the intervention period and for at least 16 weeks (112 days) after the last dose of study intervention
* If male, agrees to refrain from donating blood or sperm for the duration of the study and for 16 weeks (112 days) after the last dose of study intervention
* If female, agrees to refrain from donating blood, eggs, or ovum for the duration of the study and for at least 16 weeks (112 days) after the last dose of study intervention
Exclusion Criteria
* History of left-sided heart disease, including valvular disease (eg, moderate or greater mitral or aortic regurgitation or stenosis), left ventricular outflow tract obstruction, and/or left heart failure (eg, restrictive or dilated cardiomyopathy)
* Severe (as based on the opinion of the investigator) congenital or developmental abnormalities of the lung, thorax, and/or diaphragm
* History of Eisenmenger syndrome, Potts shunt, or atrial septostomy
* Unrepaired or residual cardiac shunt
* Diagnosis of pulmonary veno-occlusive diseases, pulmonary capillary hemangiomatosis, or overt signs of capillary and/or venous involvement
* PAH associated with portal hypertension
* Known visceral (lung, liver, or brain) arteriovenous malformation(s)
* History of full or partial pneumonectomy
* Untreated more than mild obstructive sleep apnea
* History of known pericardial constriction
* Family history of sudden cardiac death or long QT syndrome
* Any current or prior history of symptomatic coronary disease (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or cardiac anginal chest pain) within 6 months before Screening
* Cerebrovascular accident within 3 months before Screening
* Prior exposure to sotatercept or luspatercept or has had an allergic reaction to any of their excipients
DRUG: Sotatercept
Pulmonary Arterial Hypertension
Effectiveness of Nontraditional Hydroxyurea Algorithms: Novel and Clinical Evaluations (ENHANCE) (ENHANCE)
Charles T. Quinn, M.D., M.S. - charles.quinn@cchmc.org
ALL
6 month(s) and over
PHASE4
NCT07177300
Inclusion Criteria:
* Diagnosis of sickle cell anemia (HbSS) or sickle-β0-thalassemia (HbSβ0)
* Age 6 months at the time of enrollment
* Clinical decision by patient, family, and healthcare provider to initiate hydroxyurea therapy
Exclusion Criteria:
* Current treatment with regularly scheduled blood transfusions
* Sickle-hemoglobin C disease (HbSC), sickle-β+-thalassemia (HbSβ+) DRUG: PK-optimized oral hydroxyurea at MTD until 15 years of age.
Sickle Cell Anemia (HbSS), Sickle-β0-thalassemia (HbSβ0)
sickle cell anemia, SCD, sickle cell, hydroxyurea
Lorlatinib for Newly-Diagnosed High-Grade Glioma With ROS or ALK Fusion
- cancer@cchmc.org
ALL
1 year to 21 years old
EARLY_PHASE1
NCT06333899
Inclusion Criteria:
• Patients must be ≥ 12 months and ≤ 21 years of age at the time of study enrollment on TarGeT-SCR.
• Diagnosis: Patients with newly diagnosed high-grade glioma (HGG), including diffuse intrinsic pontine gliomas (DIPG), whose tumors harbor an ALK or ROS-1 fusion alteration are eligible. Patients must have had histologically verified high-grade glioma from diagnostic biopsy or resection. For the diagnosis of DIPG, patients must have a tumor with pontine epicenter and diffuse involvement of at least 2/3 of the pons, with histopathology consistent with diffuse WHO Grade 2-4. All other HGGs must be Grade 3 or 4.
• Disease Status: Patients with disseminated DIPG or HGG are eligible only if the patient is to receive chemotherapy only, i.e. no craniospinal RT is intended to be given. MRI of spine must be performed if disseminated disease is suspected clinically by the treating physicians. Patients with primary spinal tumors are eligible only if the patient is to receive either chemotherapy or focal radiation therapy, i.e., no craniospinal RT is intended to be given. Patients with leptomeningeal disease only, with no definitive identifiable primary tumor, and documented ALK or ROS-1 fusion, must be discussed with the Study Chair on a case-by-case basis.
• Performance Level: Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age (See Appendix I). Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
• Prior Therapy: * Patients must not have received any prior anti-cancer chemotherapy. * Prior use of corticosteroids is allowed (see below Exclusion Criteria)
• Organ Function Requirements 6.1 Adequate Bone Marrow Function Defined as: * Peripheral absolute neutrophil count (ANC) ≥ 1000/μL * Platelet count ≥ 100,000/μL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment) * Hemoglobin \>8 g/dL (may receive transfusions) 6.2 Adequate Renal Function Defined as: * Serum creatinine within normal institutional limits OR Creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73 m2 6.3 Adequate Liver Function Defined as: * Total bilirubin ≤ 2 × institutional upper limit of normal * AST(aspartate aminotransferase)/ALT(alanine transaminase) ≤ 2.5 × institutional upper limit of normal 6.4 Adequate Pulmonary Function Defined as: Pulse oximetry \> 94% on room air if there is clinical indication for determination (e.g. dyspnea at rest).
• 5Adequate Cardiac Function Defined as: QTc ≤ 470 msec (by Bazett formula) 6.6 Adequate Neurologic Function Defined as: Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
• 7 Informed Consent: All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines
Exclusion Criteria:
• Pregnant or breast-feeding women will not be entered on this study due to unknown risks of fetal and teratogenic adverse events as seen in animal/human studies. Pregnancy tests must be obtained in girls who are post-menarchal. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. Females of reproductive potential must use an effective non-hormonal method of contraception, since lorlatinib can render hormonal contraceptives ineffective, during study treatment and for at least 6 months after the final dose. Males with female partners of reproductive potential must use effective contraception during treatment with lorlatinib and for 3 months after the final dose.
• Concomitant Medications * Investigational Agents/Drugs: Patients who have previously received or are currently receiving another investigational drug are not eligible. * Anti-cancer Agents: Patients who have previously received or are currently receiving other anti-cancer agents, including chemotherapy, immunotherapy, monoclonal antibodies, biologic or targeted therapy, are not eligible
• Infection: Patients must not have any active, uncontrolled systemic bacterial, viral or fungal infection.
• Patients who have received prior solid organ transplantation are not eligible.
• Patients must not have malabsorption syndrome or other condition affecting oral absorption.
• Patients must not be receiving any treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor or inducer. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to treatment with loraltinib. Moderate inducers of CYP3A4 should be avoided
• Avoid concomitant use of lorlatinib with certain CYP3A substrates, for which minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.
• P-glycoprotein (P-gp) substrates: Lorlatinib is considered a moderate P-gp inducer. Co-administration of lorlatinib with P-gp substrates including but not limited to digoxin should be avoided as the concentration of these drugs may be reduced by lorlatinib.
• Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.
• Patients with a known personal history of acute or chronic severe psychiatric disorders or current history of suicidal ideation and history of suicide attempt.
DRUG: Lorlatinib, DRUG: Lorlatinib with chemotherapy1, DRUG: Lorlatinib with chemotherapy 2, DRUG: Lorlatinib post Radiation
High Grade Glioma, Diffuse Intrinsic Pontine Glioma, Anaplastic Astrocytoma, Infant Type Hemispheric Glioma, Glioblastoma, Glioblastoma Multiforme, WHO Grade III Glioma, WHO Grade IV Glioma, Diffuse Midline Glioma, H3K27-altered
ALK fusion, ROS fusion, High Grade Glioma, Diffuse Intrinsic Pontine Glioma
BEATRIX: A Study to Learn About a Group B Streptococcus Vaccine in Healthy Pregnant Women and Their Babies
Natalie Brinkmann - natalie.brinkmann@cchmc.org
ALL
1 day to 49 years old
PHASE3
NCT07160244
Key Inclusion criteria- Maternal:
* Healthy pregnant women ≤49 years of age who are between 24 0/7 and 36 0/7 weeks of gestation on the day of planned vaccination, with an uncomplicated, singleton pregnancy, and who have no known increased risk of complications.
* Had a fetal anomaly ultrasound examination with no significant fetal abnormalities observed.
* Documented negative human immunodeficiency virus (HIV) antibody test, syphilis test, and hepatitis B virus (HBV) surface antigen test during this pregnancy and prior to randomization.
* Capable of giving personal signed informed consent.
* Willing to give informed consent for her infant to participate in the study.
Key Exclusion criteria- Maternal:
* Prepregnancy body mass index (BMI) of \>40 kg/m2.
* Current pregnancy complications or abnormalities that may increase the risk associated with the participation in and completion of the study.
* Prior pregnancy complications or abnormalities that, based on the investigator's judgment, may increase the risk associated with the participation in and completion of the study.
* History of microbiologically proven invasive disease caused by GBS in the current pregnancy.
* A known or suspected infection during the current pregnancy that may increase the risk of complications in pregnancy (eg, active tuberculosis, syphilis, primary genital herpes simplex, malaria).
Key Inclusion criteria- Infant Participants
\- Evidence of a signed and dated ICD signed by the parent(s)/legally authorized representative or legal guardian
Key Exclusion Criteria - Infant Participants:
\- Children or grandchildren who are direct descendants of investigator site staff or sponsor and sponsor delegate employees directly involved in the conduct of the study.
Key Exclusion Criteria - Infant immunogenicity subset Participants:
\- Children with a known or suspected contraindication to any vaccine administered in the infant vaccine immunogenicity subset.
Refer to the study contact for further eligibility details
BIOLOGICAL: Multivalent Group B streptococcus vaccine, BIOLOGICAL: Placebo, BIOLOGICAL: Infanrix hexa, BIOLOGICAL: Prevenar 20, BIOLOGICAL: Pediarix, BIOLOGICAL: Prevnar 20, BIOLOGICAL: Infanrix
Healthy
group B streptococcus, maternal immunization, vaccine
Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS (TRIPS)
Abigayle Gibson - abigayle.gibson@cchmc.org
ALL
1 day to 17 years old
PHASE2
NCT05267821
Inclusion Criteria:
* ≥ 40 weeks corrected gestational age to \< 18 years; AND
* Admission to the PICU or CICU; AND
* Onset of ≥ 2 new organ dysfunctions within the last 3 calendar days (compared to pre-sepsis baseline) as measured by the modified Proulx criteria; AND
* Documented or suspected infection as the MODS inciting event.
Exclusion Criteria:
* Weight \<3kg; OR
* Limitation of care order at the time of screening; OR
* Patients at high likelihood of progression to brain death in opinion of the clinical team; OR
* Moribund condition in which the patient is unlikely to survive the next 48 hours in opinion of the clinical team; OR
* Current or prior diagnosis of hemophagocytic lymphohistiocytosis or macrophage activation syndrome; OR
* Peripheral white blood cell count \< 1,000 cells/mm3 as the result of myeloablative therapy OR receipt of myeloablative therapy within the previous 14 days; OR
* Known allergy to anakinra, or E. coli-derived products; OR
* Known pregnancy; OR
* Lactating females; OR
* Receipt of anakinra within the previous 28 days; OR
* Resolution of MODS by MODS Day 2; OR
* Previous enrollment in the TRIPS study. DRUG: Anakinra, DRUG: Placebo
Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)
A Study to Investigate Efficacy and Safety of Teplizumab Compared With Placebo in Participants 1 to 25 Years of Age With Stage 3 Type 1 Diabetes (βETA PRESERVE)
Cierra Farrell - cierra.farrell@cchmc.org
ALL
1 year to 25 years old
PHASE3
NCT07088068
Inclusion Criteria:
* Participants are eligible to be included in the study only if all of the following criteria apply:
* Participant must be 1 to 25 years of age inclusive, at the time of signing the informed consent.
* Participants diagnosed with T1D Stage 3 according to American Diabetes Association 2025 criteria
* Participants able to be randomized and initiate study drug within 8 weeks (56 days) of the Stage 3 T1D diagnosis
* Participants must be positive for at least one T1D autoantibody at screening:
* Glutamic acid decarboxylase (GAD-65),
* Insulinoma Antigen-2 (IA-2),
* Zinc-transporter 8 (ZnT8), or
* Insulin (if obtained not later than 14 days after exogenous insulin therapy initiation).
* Islet cell cytoplasmic autoantibodies (ICAs)
* Have random C-peptide level ≥0.2 nmol/L obtained at screening
* Enter Inclusion Criteria Sex
* Both male and female participants are eligible.
* Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* A female participant is eligible to participate if she is not pregnant, and one of the following conditions applies:
* Is a woman of nonchildbearing potential (WONCBP) OR
* Is a woman of childbearing potential (WOCBP) and agrees to use a contraceptive method that is highly effective, with a failure rate of \<1% during the study intervention period (to be effective before starting the intervention) and for at least 30 days after the last administration of study intervention.
* A WOCBP must have a negative highly sensitive pregnancy test at screening (serum) and within 24 hours (urine or serum as required by local regulations) before the first administration of study intervention.
* Lactating woman must interrupt breastfeeding and pump and discard breast milk during and for 20 days after last administration of study intervention.
* Capable of giving signed informed consent as described in Appendix 1 of the protocol which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in the protocol.
Note: For minor participants, a specific ICF must also be signed by the participant's legally authorized representative (LAR).
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
* Participant has diabetes other than autoimmune T1D that includes but is not limited to genetic forms of diabetes, maturity-onset diabetes of the young (MODY), diabetes secondary to medications or surgery and type 2 diabetes by judgement of the Investigator.
* Participant has an active serious infection and/or fever ≥38.5°C (101.3°F) within the 48 hours prior to the first dose (except if localized skin infection), or has chronic, recurrent or opportunistic infectious disease.
* At screening, participant has laboratory or clinical evidence of acute or clinically active infection with Epstein-Barr virus (EBV), cytomegalovirus (CMV).
* At screening, participant has positive serology for human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C (HCV).
* Participant has evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior anterior and lateral), and/or TB testing. Blood testing (eg, QuantiFERON® TB Gold test) is strongly preferred; if not available, any local approved TB test is allowed.
* Has other autoimmune diseases, (eg, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, multiple sclerosis, systemic lupus erythematosus etc), except clinically stable autoimmune thyroid disease, or controlled celiac disease (at discretion of Investigator).
* Any clinically significant abnormality identified either in medical/surgical history or during screening evaluation (eg, physical examination, laboratory tests, vital signs), or any adverse event (AE) during screening period which, in the judgment of the investigator, would preclude safe completion of the study or constrains efficacy assessment.
* Participant has recent or planned vaccinations as follows:
* Live-attenuated (live) vaccines (eg, varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, and smallpox) within the 8 weeks before first dose of the investigational medicinal product (IMP) or planned/required administration during treatment or up to 26 weeks after last IMP administration in any treatment course
* Inactivated or mRNA vaccines within 2 weeks before the first dose of IMP or planned required administration during treatment or up to 6 weeks after last IMP administration in any treatment course.
* Current or prior use (within 30 days before screening) of any anti-hyperglycemic agents other than insulin
* Past (within 30 days prior to screening) or current administration of any treatment that is known to cause a significant, ongoing change in the course of T1D or immunologic status, including but not limited to systemic corticosteroids (ie, oral, high doses of inhaled or injectable) with duration \>14 days, adrenocorticotropic hormone, verapamil).
* Past systemic immunosuppression medicine or immune modulatory biologic therapy (such as monoclonal antibodies), within 3 months or 5 half-lifes (whichever is longer) prior to dosing.
* Current or prior (within 30 days before screening) use of any medication known to significantly influence glucose tolerance (eg, atypical antipsychotics, diphenylhydantoin, niacin).
* Participant has previously received teplizumab or other anti-CD3 treatment.
* Other medications not compatible or interfering with IMP at discretion of Investigator.
* Current enrollment OR past participation in another investigational study in which an investigational intervention (eg, drug, vaccine, invasive device) was administered within the last 8 weeks or 5 half-lifes, whichever is longer, prior to screening.
* Participant has any of the following laboratory parameters, at screening prior to first dose:
* Lymphocyte count: \<1000/µL,
* Neutrophil count: \<1500/µL (\< 1000 /µL in participants with documented Duffy-null genotype),
* Platelet count: \<150,000 platelets/µL,
* Hemoglobin: \<10 g/dL,
* Aspartate aminotransferase (AST) \>2.0 × upper limit of normal (ULN),
* Alanine aminotransferase (ALT) \>2.0 × ULN,
* Total bilirubin \>1.5 × ULN with the exception of participants with the diagnosis of Gilbert's syndrome who may be eligible provided they have no other causes leading to hyperbilirubinemia
The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial. DRUG: Teplizumab, OTHER: Placebo
Type 1 Diabetes Mellitus
Checkpoint Inhibition In Pediatric Hepatocellular Carcinoma
- cancer@cchmc.org
ALL
0 years to 30 years old
PHASE2
NCT04134559
Inclusion Criteria:
* Age: Patients must be \<30 years of age at the time of study enrollment.
* Diagnosis: Patients must have relapsed/refractory, histologically confirmed HCC to be eligible for enrollment. Patients with hepatocellular neoplasm not otherwise specified (HCN NOS) will also be eligible.
* Disease Status: Participants must have measurable disease by RECIST criteria, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) measured at ≥20 mm with conventional technique or ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. See Section 10 for the evaluation of measurable disease.
* Performance Level: Karnofsky performance status ≥ 60% for patients ≥ 16 years of age or Lansky ≥ 60% for patients \< 16 years of age.
* Prior Therapy: Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy.
* Patients must not have received standard or targeted treatment regimens within 14 days of initiation of treatment with pembrolizumab.
* Patients must not have received prior radiotherapy within 7 days of initiation of treatment with pembrolizumab. Patients who have experienced radiation-induced adverse events must recover to a grade 1 prior to enrollment.
* Organ Function Requirements: Participants must have normal organ and marrow function as defined below:
* Adequate Bone Marrow Function defined as:
* Peripheral absolute neutrophil count (ANC) ≥ 750/μL
* Platelet count ≥ 75,000/μL (can be transfused)
* Adequate Liver Function defined as:
* Total bilirubin \< 1.5 x institutional upper limit of normal (ULN)
* AST(SGOT) ≤ 2.5 x ULN
* ALT(SGPT) ≤ 2.5 x ULN
* If liver function studies are more elevated than the thresholds above, and if if this elevation is felt secondary to tumor, patients may still be eligible for enrollment after discussion with the study PI.
* Adequate Renal and Metabolic Function defined as:
* A serum creatinine based on age/gender as follows:
* 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
* OR
* Creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels above institutional normal.
* Amylase ≤ 1.5 x ULN
* Lipase ≤ 1.5 x ULN
* If liver function studies are more elevated than the thresholds above, and if this elevation is felt secondary to tumor, patients may still be eligible for enrollment after discussion with the study PI.
\-- Adequate Thyroid Function defined as:
\--- TSH ≤1.5 ULN. Patients can be receiving thyroid supplementation.
* Confirmation of Insurance Pre-authorization approval for Pembrolizumab.
* Patients, their parent, and/or legally authorized representative must be able to understand and be willing to sign a written informed consent document. Assent for participants \< 18 years will follow institutional guidelines. The protocol will require approval by each institution's Institutional Review Board.
* The effects of pembrolizumab on the developing human fetus are unknown. For this reason, patients of child-bearing and child-fathering potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 4 months after completion of pembrolizumab administration. Should a female become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of pembrolizumab administration.
* Women of child bearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours of each treatment.
* A tumor sample must be available for submission to the central laboratory (Dana-Farber Cancer Institute, see Section 9). If surgery was performed at the time of recurrence, this sample, in addition to a diagnostic sample should be submitted. If no re-operation was performed, archived tissue from diagnosis or the most recent procedure should be submitted (see section 9 for further details regarding tissue specifications).
Exclusion Criteria:
* Participants who are receiving any other investigational agents are not eligible.
* Participants who have received checkpoint inhibitors (PD-1, PD-L1, and CTLA-4 inhibitors) are not eligible.
* Participants who have received antibody-based therapies are not eligible if they are within 3 half-lives of receipt of the last antibody dose.
* Participants who are receiving chronic steroids are not eligible.Chronic steroids are defined as either \> or = 2mg/kg/day of body weight or \> or = 20mg/day of prednisone or equivalent for persons who weigh \> or = 10kg administered for \> or = 14 consecutive days.
* Participants who are receiving anti-inflammatory or immunosuppressive medications are not eligible.
* Participants with known autoimmune disease, with the exceptions of childhood asthma or atopic dermatitis, are not eligible.
* Patients with a history of a positive test for human immunodeficiency virus or acquired immunodeficiency syndrome are not eligible.
* Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to pembrolizumab are not eligible. History of severe allergy to monoclonal antibody therapies (i.e. anaphylaxis) are likewise an exclusion.
* Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements are not eligible.
* Patients with prior solid organ transplantation are not eligible. DRUG: Pembrolizumab
Hepatocellular Carcinoma, Childhood, Fibrolamellar Carcinoma, Liver Cancer, Liver Cancer, Pediatric
Hepatocellular Carcinoma Childhood, Fibrolamellar Carcinoma, Liver Cancer, Liver Cancer Pediatric
A Study to Compare Standard Chemotherapy to Therapy With CPX-351 and/or Gilteritinib for Patients With Newly Diagnosed AML With or Without FLT3 Mutations
- cancer@cchmc.org
ALL
6 months to 21 years old
PHASE3
NCT04293562
Inclusion Criteria:
* All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831. Bone marrow and/or blood must have been submitted to the BPC via APEC14B1 for testing of FLT3 markers. Patients without samples submitted for FLT3 testing are not eligible
* Patients must be at least 6 months of age and less than 22 years of age at the time of study enrollment
* Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
* Patient must have 1 of the following:
* \>= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
* In cases where extensive fibrosis may result in a dry tap, blast count can be obtained from touch imprints or estimated from an adequate bone marrow core biopsy
* \< 20% bone marrow blasts with one or more of the genetic abnormalities associated with childhood/young adult AML as provided in the protocol (sample obtained within 14 days prior to enrollment)
* A complete blood count (CBC) documenting the presence of at least 1,000/uL (i.e., a white blood cell \[WBC\] count \>= 10,000/uL with \>= 10% blasts or a WBC count of \>= 5,000/uL with \>= 20% blasts) circulating leukemic cells (blasts) if a bone marrow aspirate or biopsy is pending or cannot be performed (performed within 7 days prior to enrollment)
* ARM C: Patient must be \>= 2 years of age at the time of Late Callback
* ARM C: Patient must have FLT3/ITD allelic ratio \> 0.1 as reported by Molecular Oncology
* ARM C: Patient does not have any congenital long QT syndrome or congenital heart block
* ARM C: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
* ARM C: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
* ARM C: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
* ARM D: Patient must be \>= 2 years of age at the time of Late Callback
* ARM D: Patient must have one of the clinically relevant non-ITD FLT3 activating mutations as reported by Foundation Medicine
* ARM D: Females of reproductive potential must agree to use effective contraception during treatment and for at least 6 months after the last dose of gilteritinib
* ARM D: Lactating women must agree not to breastfeed during treatment with gilteritinib and for 2 months after the last dose of gilteritinib
* ARM D: Males of reproductive potential must agree to use effective contraception during treatment and for at least 4 months after the last dose of gilteritinib
* NEUROPSYCHOLOGICAL TESTING: Patient must be enrolled on Arm A or Arm B. Patients who transfer to Arm C or Arm D are not eligible
* NEUROPSYCHOLOGICAL TESTING: Patient must be 5 years or older at the time of enrollment
* NEUROPSYCHOLOGICAL TESTING: English-, French- or Spanish-speaking
* NEUROPSYCHOLOGICAL TESTING: No known history of neurodevelopmental disorder prior to diagnosis of AML (e.g., Down syndrome, fragile X, William syndrome, mental retardation)
* NEUROPSYCHOLOGICAL TESTING: No significant visual or motor impairment that would prevent computer use or recognition of visual test stimuli
* 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
Exclusion Criteria:
* Fanconi anemia
* Shwachman Diamond syndrome
* Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
* Telomere disorders
* Germline predispositions known, or suspected by the treating physician to increase risk of toxicity with AML therapy
* Any concurrent malignancy
* Juvenile myelomonocytic leukemia (JMML)
* Philadelphia chromosome positive AML
* Mixed phenotype acute leukemia
* Acute promyelocytic leukemia
* Acute myeloid leukemia arising from myelodysplasia
* Therapy-related myeloid neoplasms
* Patients with persistent cardiac dysfunction prior to enrollment, defined as ejection fraction (EF) \< 50% (preferred method Biplane Simpson's EF) or if EF unavailable, shortening fraction (SF) \< 24%. \*Note: if clinically safe and feasible, repeat echocardiogram is strongly advised in order to confirm cardiac dysfunction following clinical stabilization, particularly if occurring in the setting of sepsis or other transient physiologic stressor. If the repeat echocardiogram demonstrates an EF \>= 50%, the patient is eligible to enroll and may receive an anthracycline-containing Induction regimen
* Administration of prior anti-cancer therapy except as outlined below:
* Hydroxyurea
* All-trans retinoic acid (ATRA)
* Corticosteroids (any route)
* Intrathecal therapy given at diagnosis
* In particular, strong inducers of CYP3A4 and/or P-glycoprotein (P-gp) should be avoided from the time of enrollment until it is determined whether the patient will receive gilteritinib. Patients receiving gilteritinib will be required to avoid strong CYP3A4 inducers and/or strong P-gp inducers for the duration of the study treatment
* Patients \< 8.3 kg at study enrollment are not eligible
* 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
* ARM D: Patient does not have any congenital long QT syndrome or congenital heart block PROCEDURE: Allogeneic Hematopoietic Stem Cell Transplantation, DRUG: Asparaginase Erwinia chrysanthemi, PROCEDURE: Biospecimen Collection, PROCEDURE: Bone Marrow Aspiration, PROCEDURE: Bone Marrow Biopsy, PROCEDURE: Computed Tomography, DRUG: Cytarabine, DRUG: Daunorubicin Hydrochloride, DRUG: Dexrazoxane Hydrochloride, DRUG: Etoposide, OTHER: Fludeoxyglucose F-18, DRUG: Gemtuzumab Ozogamicin, DRUG: Gilteritinib Fumarate, DRUG: Liposome-encapsulated Daunorubicin-Cytarabine, PROCEDURE: Magnetic Resonance Imaging, DRUG: Methotrexate, DRUG: Mitoxantrone Hydrochloride, PROCEDURE: Positron Emission Tomography, OTHER: Questionnaire Administration, DRUG: Therapeutic Hydrocortisone
Acute Myeloid Leukemia
KiteLock 4% EDTA Lock Solution for the Prevention of Occlusions in Children With Intestinal Failure
Crystal Slaughter - crystal.slaughter@cchmc.org
ALL
4 weeks to 18 years old
NA
NCT05879835
Inclusion Criteria:
• Patients managed by the intestinal rehabilitation program at one of the participating centers.
• Diagnosis of intestinal failure defined as need for PN support for \>60 days in previous 74 days for primary intestinal disease (short bowel syndrome, primary motility disorder, mucosal enteropathy).
• Expectation of the treating physician that the patient will require PN for at least 6 months following enrollment.
• Age less than 18 years at diagnosis but greater than 4 weeks chronological age or 40 weeks estimated gestational age, whichever is greater.
• Stable TPN cycling (4 hours off TPN minimum per day) enabling home TPN management
• Presence of a tunneled central venous catheter (CVC), port-a-catheter, or peripherally inserted central catheter (PICC).
• Clinical stability for at least 4 weeks and no acute medical comorbidities.
• A minimum dwell time of 4 consecutive hours daily.
• Care provider willing to provide informed consent to participate in the trial and willing to comply with randomization and study protocol.
Exclusion Criteria:
• A temporary CVC (jugular or femoral) or peripheral catheter.
• Patients receiving long-term PN, but not due to a primary intestinal disorder (i.e., oncology patients or premature neonates on PN due to intestinal immaturity).
• Known hypersensitivity, allergy, or reaction to EDTA.
• Pregnancy or nursing mother.
• Participation in another investigational device or drug trial within 30 days prior to enrollment (unless approved by the principal investigators of the trial).
• Severe coagulopathy (platelets \<50,000, or INR \> 1.5).
• Diagnosis of immunodeficiency disorder.
• Unstable medical condition requiring hospital admission
• Received antibiotic therapy for CLABSI within last 14 days.
DEVICE: KiteLock 4% Sterile Catheter Lock Solution, DEVICE: Heparin Lock Solution
Pediatric Intestinal Failure
catheter lock solution, pediatric intestinal failure, intestinal failure, central venous catheter, KiteLock 4%, heparin, total parenteral nutrition, parenteral nutrition
A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD) (AGAVE-201)
Sara Loveless - sara.loveless@cchmc.org
ALL
2 years and over
PHASE2
NCT04710576
Inclusion Criteria:
• Participants must be 2 years of age or older, at the time of signing the informed consent.
• Participants who are allogeneic hematopoietic stem cell transplantation (HSCT) recipients with active cGVHD requiring systemic immune suppression. Active cGVHD is defined as the presence of signs and symptoms of cGVHD per 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
• Participants with refractory or recurrent active cGVHD despite at least 2 lines of systemic therapy. * Refractory disease defined as meeting any of the following criteria: * The development of 1 or more new sites of disease while being treated for cGVHD. * Progression of existing sites of disease despite at least 1 month of standard or investigation therapy for cGVHD. * Participants who have not achieved a response within 3 months on their prior therapy for cGVHD and for whom the treating physician believes a new systemic therapy is required. * Recurrent cGVHD is active, symptomatic disease (after an initial response to prior therapy) as defined, based on the NIH 2014 consensus criteria, by organ-specific or global assessment or for which the physician believes that a new line of systemic therapy is required.
• Participants may have persistent, active acute and cGVHD manifestations (overlap syndrome), as defined by 2014 NIH Consensus Development Project on Criteria for Clinical trials in cGVHD.
• Karnofsky Performance Scale of ≥60 (if aged 16 years or older); Lansky Performance Score of ≥60 (if aged \<16 years)
• Adequate organ and bone marrow functions evaluated during the 14 days prior to randomization.
• Creatinine clearance (CrCl) ≥30 milliliter/minute based on the Cockcroft-Gault formula in adult participants and Schwartz formula in pediatric participants.
• Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• Concomitant use a of systemic corticosteroid is allowed but not required. Topical and inhaled corticosteroid agents are allowed. If a participant is taking corticosteroids at study randomization, they must be on a stable dose of corticosteroids for at least 2 weeks prior to Cycle 1 Day 1.
• Concomitant use of CNI or mammalian target of repamycin (mTOR) inhibitors (sirolimus or everolimus) is allowed but not required.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and protocol. A parent/guardian should provide consent for pediatric participants unable to provide consent themselves; in addition, where applicable pediatric participants should sign their own assent form.
Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
• Has acute GVHD without manifestations of cGVHD.
• Any evidence (histologic, cytogenetic, molecular, hematologic, or mixed) of relapse of the underlying cancer or post-transplant lymphoproliferative disease at the time of screening.
• History of acute or chronic pancreatitis.
• History of myositis.
• History or other evidence of severe illness, uncontrolled infection or any other conditions that would make the participant, in the opinion of the Investigator, unsuitable for the study.
• Participants with acquired immune deficiency syndrome (AIDS).
• Hepatitis B (defined as hepatitis B virus \[HBV\] surface antigen positive and HBV core antibody positive, with positive HBV deoxyribonucleic acid \[DNA\], or HBV positive core antibody alone with positive HBV DNA. Hepatitis C (defined as positive hepatitis C \[HCV\] antibody with positive HCV ribonucleic acid \[RNA\]).
• Diagnosed with another malignancy (other than malignancy for which transplant was performed) within 3 years of randomization, unless previously treated with curative intent and approved by Sponsor's Medical Monitor (for example, completely resected basal cell or squamous cell carcinoma of the skin, resected in situ cervical malignancy, resected breast ductal carcinoma in situ, or low-risk prostate cancer after curative resection).
• Female participant who is pregnant or breastfeeding.
• Previous exposure to CSF1-R targeted therapies.
• Taking agents for treatment of cGVHD other than corticosteroids or either a CNI or mTOR inhibitor is prohibited.
• For approved or commonly used agents, other than corticosteroids, CNI and mTOR inhibitor, a washout of 2 weeks or 5 half-lives, whichever is shorter, is required at study enrollment.
• Receiving another investigational treatment within 28 days of randomization.
• Participants should not be participating in any other interventional study. Pediatric participants are encouraged to also participate in the ongoing developmental studies of the Pediatric cGVHD Symptom Scale (PCSS).
DRUG: Axatilimab
Chronic Graft-versus-host-disease
cGVHD, AGAVE-201, GVHD, graft versus host disease, graft-versus-host-disease
Pediatric Pulmonary Hypertension Network (PPHNet) Informatics Registry (PPHNet)
Sarah Speed - sarah.speed@cchmc.org
ALL
1 day to 21 years old
NCT02249923
Inclusion Criteria:
* The subject's age of onset of pulmonary hypertension must be prior to age 18 years
* The person providing consent must be able to read either Spanish or English.
* The subject (and/or parent/legal guardian) must be able to provide informed consent
Exclusion Criteria:
* Diagnosed with pulmonary hypertension after age 18
* Refusal to sign informed consent Pulmonary Vascular Disease, Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension (PAH), Pulmonary Vascular Disease (PVD), Registry, Pediatric
Evaluation of Analgesia for Spine Fusion Elective Surgery in Children (PRECISE)
Kristie Geisler - kristie.geisler@cchmc.org
ALL
10 years to 18 years old
PHASE3
NCT06626503
Inclusion Criteria:
• Age 10 - \< 18 years
• American Society of Anesthesiologists (ASA) Physical Status 1 or 2
• Undergoing PSF for idiopathic scoliosis
• Participant or legal guardian can speak and read English or Spanish
Exclusion Criteria:
• Pregnant patients
• Methadone allergy
• Preoperative prolonged QTc more than 460 msec (-30 days to 0 day)
• Subjects undergoing concomitant treatment with known cytochrome P450 inhibitors included in methadone labeling (i.e. macrolides (e.g. erythromycin), azole-antifungal agents (e.g. ketoconazole, voriconazole), protease inhibitors (e.g. ritonavir), fluconazole, SSRIs (e.g. sertraline, fluvoxamine)
• Preoperative opioid use within 30 days before surgery
• History of severe sleep apnea, defined as a prior sleep study demonstrating an apnea-hypopnea index (AHI) greater than 10.
• Significant liver, kidney, neurological disease, developmental delay, or any other co-existing medical condition per discretion of the clinical investigator
DRUG: Methadone based ERAS, DRUG: Non-methadone based group
Idiopathic Scoliosis
A Study to Evaluate the Safety, Efficacy, PK, PD and Immunogenicity of Cipaglucosidase Alfa/Miglustat in IOPD Subjects Aged 0 to <18 (ROSSELLA)
Laurie Bailey - laurie.bailey@cchmc.org
ALL
Up to 17 years old
PHASE3
NCT04808505
Inclusion Criteria:
Cohort 1:
• Male or female subjects who are aged 6 months to \< 18 years on Day 1
• Subject must have documentation of IOPD genotype
• Subject must have had hypertrophic cardiomyopathy at the time of diagnosis
• Subject must have received ERT for at least 6 months immediately before enrollment. For subjects whose ERT dosage has been modified, the subject must have been on the modified dosage and regimen for at least 3 months before enrollment
• Subjects aged ≥ 12 to \< 18 years must perform one valid 6-minute walk test (6MWT) (≥ 75 meters) at screening; Subjects aged ≥ 5 to \< 12 years must perform one valid 6MWT (≥ 40 meters) at screening; Subjects aged 18 months to \< 5 years must be ambulatory and assessed to be likely to be able to perform 6MWT (≥ 40 meters) when they turn 5 years old
• Subjects must have experienced a clinical decline on their current rhGAA dose and frequency Cohort 2:
• Male or female subjects who are aged 0 to \<6 months at Day 1
• Subject must have documentation of IOPD genotype
• Subject must have had hypertrophic cardiomyopathy at the time of diagnosis
• Subject is ERT-naïve Long-term Extension (Cohort 1 or Cohort 2): 1\. Subject must have, in the opinion of the investigator, benefited from therapy with cipaglucosidase alfa/miglustat during the 104-week primary treatment period with no significant safety concerns.
Exclusion Criteria:
Cohort 1 and Cohort 2, unless specified
• Subject requires invasive ventilation (eg, tracheostomy)
• Subject is CRIM negative and has not received prophylactic immunomodulation (Cohort 1); Subject is CRIM negative and will not be receiving prophylactic immunomodulation (Cohort 2)
• Subject has a history of life-threatening IARs/hypersensitivity (eg, anaphylaxis and severe cutaneous reactions) to ERT (eg, alglucosidase alfa, cipaglucosidase alfa, miglustat) or other iminosugars, or to any of the excipients, where rechallenge was unsuccessful
• Subject has prior history of illness or condition known to affect motor function
• Female subject is pregnant (or intends to get pregnant) or breastfeeding at screening (Cohort 1)
BIOLOGICAL: Cipaglucosidase alfa, DRUG: Miglustat
Glycogen Storage Disease Type II Infantile Onset
Motor Training for Infants With Cerebral Palsy
Karen L Harpster, PhD, OTR/L - karen.harpster@cchmc.org
ALL
3 months to 8 months old
NA
NCT04886895
Inclusion Criteria:
* Age at enrollment: between 3-8 months corrected age
* Caregivers fluent in English
* Preterm infants with objectively defined severe diffuse white matter abnormality on MRI at term OR
* High-risk infants (e.g., preterm, neonatal hypoxic-ischemic encephalopathy, perinatal stroke) with moderate-severe injury on structural MRI or cranial ultrasound (e.g., basal ganglia/thalamic signal intensity, cystic periventricular leukomalacia, encephalomalacia, large stroke, and/or severe intraventricular/periventricular hemorrhage) at around term-equivalent age or before Neonatal Intensive Care Unit discharge AND either:
* "Absent" fidgety movements based on the Prechtl General Movement Assessment (GMA) between 3-4 months corrected age OR
* A score of 56 or below on the Hammersmith Infant Neuromotor Examination (HINE) between 3-6 months corrected age (31)
Exclusion Criteria:
* Medical conditions that restrict active participation such as oxygen dependence
* Infants with significant visual deficits defined by the inability to track an object horizontally
* Living in a remote location prohibiting drives to the hospital every other week. OTHER: Let's Move Motor Intervention
Cerebral Palsy
motor skills, occupational therapy, physical therapy
A-LiNK: Improving Outcomes in Autoimmune Liver Disease (ALINK)
Cyd M Castro-Rojas, PhD - Cyd.CastroRojas@cchmc.org
ALL
NCT05750498
Inclusion Criteria:
* Clinical diagnosis of autoimmune hepatitis (AIH)
* Clinical diagnosis of primary sclerosing cholangitis (PSC)
* Clinical diagnosis of autoimmune sclerosing cholangitis (ASC)
Exclusion Criteria:
• History of liver transplant OTHER: No interventions
Autoimmune Hepatitis, Primary Sclerosing Cholangitis
Pediatrics, Autoimmune Hepatitis, Primary Sclerosing Cholangitis, Autoimmune Sclerosing Cholangitis, Chronic Liver Disease, End-stage Liver Disease, Clinical Registry, Research Registry, Quality Improvement, Outcomes Research, Comparative Effectiveness Research, Patient Reported Outcomes, Health Services Research
A Study About How Blood Cell Growth Patterns Relate to Heart Health After Treatment for Hodgkin Lymphoma
- cancer@cchmc.org
ALL
7 years and over
NCT05705531
Inclusion Criteria:
* Patient must be \>= 7 years of age at the time of enrollment (age to perform an MRI without sedation).
* History of pathologically confirmed classical Hodgkin Lymphoma (cHL) initially diagnosed when the patient was \>= 2 and \< 22 years of age.
* As part of frontline therapy for cHL, the patient must have received a cumulative doxorubicin equivalent anthracycline dose of ≥ 200 mg/m\^2 as estimated in doxorubicin isotoxic equivalents dose conversion calculation.
* Note: History of COG therapeutic trial participation is not required. Institutional records (e.g., clinic note, treatment summary, chemotherapy roadmap) can be used as reference documentation of receipt of anthracycline dose.
* All systemic cancer treatment must have been completed ≥ 2 years prior to study enrollment.
* Not known to have had a primary event (relapse/second malignancy/death).
* Note: Subjects treated at another institution are eligible if they are now being followed at the current COG institution, if the study procedures can be performed and the data accessible by a COG institution where the study is open.
* Patient must have access to cardiac MRI at the enrolling institution and must be able to complete cardiac MRI without sedation.
Exclusion Criteria:
* Medical contraindication to undergoing a non-contrast cardiac MRI.
* Patients with nodular lymphocyte-predominant HL.
* Received cancer therapy in addition to that for primary Hodgkin Disease (e.g., for disease progression or recurrence, or subsequent malignant neoplasm).
* History of CTCAE grade 3 or higher cardiovascular disease or condition known to exist prior to the patient's initial diagnosis of cHL.
* Note: exceptions are made for congenital conditions considered fully resolved by surgery and chronic conditions such as hypertension or hypercholesterolemia that are managed with medical intervention.
* History of an immunodeficiency that existed prior to cHL diagnosis, such as primary immunodeficiency syndromes, organ transplant recipients and conditions requiring systemic immunosuppressive agents. PROCEDURE: Archive Sample Retrieval, PROCEDURE: Biospecimen Collection, OTHER: Electronic Health Record Review, PROCEDURE: Magnetic Resonance Imaging, OTHER: Survey Administration
Cardiovascular Disorder, Classic Hodgkin Lymphoma, Clonal Hematopoiesis