Hematologic Malignancies
Conditions
Brief summary
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
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.
Interventions
BIOLOGICALBiological: ProHema-CB
Each subject will receive one administration of ProHema-CB unit transplant.
Sponsors
Fate Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Profile, Primarily Assessed by Neutrophil Engraftment | Neutrophil engraftment by Day 42 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ProHema-CB 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: ProHema-CB: Each subject will receive one administration of ProHema-CB unit transplant. | 3 |
| Total | 3 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | ProHema-CB |
|---|---|
| Age, Continuous | 15.7 Years STANDARD_DEVIATION 3.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 3 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 3 Participants |
| Weight (kg) | 73.4 kg STANDARD_DEVIATION 28.8 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 2 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
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.
Time frame: Neutrophil engraftment by Day 42
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| ProHema-CB | Safety Profile, Primarily Assessed by Neutrophil Engraftment | 3 Participants |