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

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

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.

Eligibility Criteria:
Inclusion Criteria:

1. Male and female subjects aged 1 to 18 years, inclusive.
2. Subjects with hematologic malignancies for whom allogeneic stem cell transplantation is deemed clinically appropriate.

   1. Acute Myelogenous Leukemia (AML) in high risk 1st or subsequent CR
   2. Acute Lymphoblastic Leukemia (ALL) in CR
   3. NK cell lymphoblastic leukemia in any CR
   4. Biphenotypic or undifferentiated leukemia in 1st or subsequent CR
   5. Myelodysplastic Syndrome (MDS) at any stage.
   6. Chronic Myelogenous Leukemia (CML) All subjects with evidence of CNS leukemia must be treated and be in CNS CR to be eligible for trial.
3. 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.
4. Availability of suitable primary and secondary umbilical cord blood (UCB) units.
5. Adequate performance status, defined as:

   1. Subjects ≥ 16 years: Karnofsky score ≥ 70%.
   2. Subjects \< 16 years: Lansky score ≥ 70%.
6. Cardiac: Left ventricular ejection fraction at rest must be \> 40%, or shortening fraction \> 26%.
7. Pulmonary:

   1. Subjects \> 10 years: DLCO (diffusion capacity) \> 50% of predicted (corrected for hemoglobin)
   2. FEV1, FVC \> 50% of predicted; Note: If unable to perform pulmonary tests, then O2 saturation \> 92% on room air.
8. 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.
9. 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.
10. Signed IRB approved Informed Consent Form (ICF).

Exclusion Criteria:

1. Female subjects that are pregnant or breastfeeding.
2. Evidence of HIV infection or HIV positive serology.
3. Current uncontrolled bacterial, viral or fungal infection.
4. Prior allogeneic hematopoietic stem cell transplant.
5. Autologous transplant \< 12 months prior to enrollment.
6. Prior autologous transplant for the disease for which the UCB transplant is being performed.
7. Active malignancy other than the one for which the UCB transplant is being performed within 12 months of enrollment.
8. Inability to receive TBI.
9. Requirement of supplemental oxygen.
10. HLA-matched related donor able to donate.
11. Use of an investigational drug within 30 days prior to screening.
12. Subject is unlikely to comply with the protocol requirements, instructions and study-related restrictions