A Phase 1 Trial of a Single ProHema® CB Product for Pediatric Patients With Hematologic Malignancies

Study Overview
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Brief Summary
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This is an open-label, safety study of a single ProHema-CB product administered following myeloablative conditioning regimen in pediatric subjects with hematologic malignancies.

Detailed Description
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A maximum of 18 eligible male and female subjects (1 to 18 years old, inclusive) will be enrolled and treated in the trial at approximately 3 to 5 centers within the U.S. These 18 subjects will consist of 3 cohorts of 6 subjects each. The cohorts will be defined by age: 1 to 4 years; > 4 to 12 years; and > 12 to 18 years. These cohorts will be enrolled simultaneously. All subjects will be admitted to the hospital, per institutional practice, and will receive a myeloablative conditioning regimen, after which they will receive an HLA-matched or partially matched ProHema-CB unit on study Day 0.

Official Title
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A Phase 1 Trial of a Single ProHema® CB Product (Ex Vivo Modulated Human Cord Blood Cells) Following Myeloablative Conditioning for Pediatric Patients With Hematologic Malignancies

Conditions
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Hematologic Malignancies

Intervention / Treatment
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* Biological: Biological: ProHema-CB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects aged 1 to 18 years, inclusive. Subjects with hematologic malignancies for whom allogeneic stem cell transplantation is deemed clinically appropriate. Acute Myelogenous Leukemia (AML) in high risk 1st or subsequent CR Acute Lymphoblastic Leukemia (ALL) in CR NK cell lymphoblastic leukemia in any CR Biphenotypic or undifferentiated leukemia in 1st or subsequent CR Myelodysplastic Syndrome (MDS) at any stage. Chronic Myelogenous Leukemia (CML) All subjects with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for trial. Lack of 5-6/6 HLA matched related or 8/8 HLA A, B, C, DRß1 matched unrelated donor; or unrelated donor not available within appropriate timeframe, as determined by the transplant physician. Availability of suitable primary and secondary umbilical cord blood (UCB) units. Adequate performance status, defined as: Subjects ≥ 16 years: Karnofsky score ≥ 70%. Subjects < 16 years: Lansky score ≥ 70%. Cardiac: Left ventricular ejection fraction at rest must be > 40%, or shortening fraction > 26%. Pulmonary: Subjects > 10 years: DLCO (diffusion capacity) > 50% of predicted (corrected for hemoglobin) FEV1, FVC > 50% of predicted; Note: If unable to perform pulmonary tests, then O2 saturation > 92% on room air. Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) > 70mL/min/1.73m2. Hepatic: Bilirubin ≤ 2.5 mg/dL (except in the case of Gilbert's syndrome or ongoing hemolytic anemia); and ALT, AST and Alkaline Phosphatase ≤ 5 × ULN. Signed IRB approved Informed Consent Form (ICF). Exclusion Criteria: Female subjects that are pregnant or breastfeeding. Evidence of HIV infection or HIV positive serology. Current uncontrolled bacterial, viral or fungal infection. Prior allogeneic hematopoietic stem cell transplant. Autologous transplant < 12 months prior to enrollment. Prior autologous transplant for the disease for which the UCB transplant is being performed. Active malignancy other than the one for which the UCB transplant is being performed within 12 months of enrollment. Inability to receive TBI. Requirement of supplemental oxygen. HLA-matched related donor able to donate. Use of an investigational drug within 30 days prior to screening. Subject is unlikely to comply with the protocol requirements, instructions and study-related restrictions

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ProHema-CB<br>All subjects will receive treatment with ProHema-CB (ex-vivo modulated human cord blood cells) transplant. ProHema-CB (the prostaglandin derivative, 16,16-dimethyl prostaglandin E2 also referred to as FT1050) will be prepared and administered in one of two formulations, based upon subject weight: For subjects > 35 kg, ProHema-CB will be administered as 150 mL product in a blood bag via gravity infusion. It will be infused at 10 mL to 15 mL per minute, for a total infusion time of 10 to 15 min. For subject's ≤ 35 kg, ProHema-CB will be administered as a 50 mL product in a syringe via syringe pump.o It will be infused at 5 mL/kg per hour for a total infusion time of up to  1 hour. | Biological: Biological: ProHema-CB<br>* Each subject will receive one administration of ProHema-CB unit transplant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile, Primarily Assessed by Neutrophil Engraftment | To describe the safety profile of ProHema-CB after myeloablative conditioning in pediatric patients with hematologic malignancies. The safety profile will primarily be assessed by neutrophil engraftment. | Neutrophil engraftment by Day 42 |