StemRegenin-1 Expanded vs Unexpanded UCB for High Risk Heme Malignancies

Study Overview
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Brief Summary
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This is an open label, interventional, randomized phase II trial comparing StemRegenin-1 (SR-1) cultured umbilical cord blood (experimental arm) to unmanipulated umbilical cord blood (standard of care arm) transplantation after a myeloablative CY/FLU/TBI conditioning. A 2:1 randomization will be employed with a higher chance of being assigned to the experimental arm.

Official Title
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Single-Center, Open Label, Randomized Trial Comparing StemRegenin-1 Expanded Versus Unmanipulated Umbilical Cord Blood Transplantation In Patients With High-Risk Malignancy

Conditions
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Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Chronic Myelogenous Leukemia, Myelodysplasia

Intervention / Treatment
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* Biological: Unmanipulated UCB
* Biological: SR-1 UCB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have a partially HLA matched UCB unit with a pre-cryopreserved TNC dose >2.5 x 107 per kilogram recipient weight. HLA matching is initially based on 4 of 6 HLA-A and B (at low or intermediate resolution by molecular typing) and DRB1 (at high resolution by molecular typing). Eligible Diseases Acute myelogenous leukemia (AML) at the following stages: Intermediate to high risk leukemia in first complete remission (CR1) based on institutional criteria. Any second or subsequent CR. Secondary AML with prior malignancy that has been in remission for at least 12 months. Acute lymphocytic leukemia (ALL) at the following stages: High risk first remission. Ph+ ALL, or MLL rearrangement with slow early response at Day 14, or Hypodiploidy (< 44 chromosomes or DNA index < 0.81), or End of induction M3 bone marrow, or End of induction M2 with M2-3 at Day 42. High risk second CR based on institutional criteria (eg, for children, bone marrow relapse <36 months from induction or T-lineage bone marrow relapse or very early isolated central nervous system (CNS) relapse <6 months from diagnosis, or slow re-induction (stage M2-3 at day 28 after induction) regardless of length remission. Any third or subsequent CR. Biphenotypic/undifferentiated leukemia in CR Chronic myelogenous leukemia (CML) excluding refractory blast crisis Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia Other Inclusion Criteria Karnofsky score >70% (16 years and older) or a Lansky play score >70 (children <16 years) - appendix II Adequate organ function defined as: Renal: Serum creatinine within normal range for age, or if serum creatinine outside normal range for age, then renal function (creatinine clearance or GFR) >70 mL/min/1.73 m2. Hepatic: Bilirubin ≤2.5 x mg/dL; AST, ALT, alkaline phosphatase <5 x upper limit of normal, Pulmonary function: DLCO, FEV1, FEC (diffusion capacity) >50% of predicted (corrected for hemoglobin); if unable to perform pulmonary function tests, then normal O2 saturation on room air. Cardiac: Left ventricular ejection fraction at rest must be >45% Available 'back-up' HSPC graft (e.g, second partially HLA matched UCB unit, haploidentical related donor). Voluntary written consent signed (adult or parental) before performance of any study-related procedure not part of normal medical care Exclusion Criteria: Pregnant or breast feeding. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. Females of childbearing potential must have a blood test or urine study within 14 days prior to study enrollment to rule out pregnancy. Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology. Active bacterial, viral or fungal infection (currently taking medication and progression of clinical symptoms). Prior autologous or allogeneic transplant within past 12 months. Other active malignancy. Inability to receive TBI 1320 cGy (e.g., extensive prior therapy including >12 months alkylator therapy or >6 months alkylator therapy with extensive radiation. Or prior Y-90 ibritumomab (Zevalin) or I-131 tostumomab (Bexxar), as part of their salvage therapy.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 35 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Unmanipulated UCB<br>Subjects will receive unmanipulated umbilical cord blood transplantation after a myeloablative CY/FLU/TBI conditioning. | Biological: Unmanipulated UCB<br>* Unmanipulated UCB infusion given on Day 0. All patients will receive the same conditioning and immunoprophylaxis for the prevention of acute and chronic GVHD, previously demonstrated to offer the best outcomes in recipients of partially HLA matched UCB. Standard supportive care, including the use of Neupogen [G-CSF] and prophylactic anti-bacterial, protozoal, viral and fungal agents, will also be prescribed. Supportive care will be modified throughout the transplant course at the treating physician's judgement.<br>* Other names: Unmanipulated Umbilical Cord Blood;|
| Experimental: StemRegenin-1 UCB<br>Subjects will receive StemRegenin-1 (SR-1) cultured umbilical cord blood transplantation after a myeloablative CY/FLU/TBI conditioning. | Biological: SR-1 UCB<br>* SR-1 UCB infusion given on Day 0. All patients will receive the same conditioning and immunoprophylaxis for the prevention of acute and chronic GVHD, previously demonstrated to offer the best outcomes in recipients of partially HLA matched UCB. Standard supportive care, including the use of Neupogen [G-CSF] and prophylactic anti-bacterial, protozoal, viral and fungal agents, will also be prescribed. Supportive care will be modified throughout the transplant course at the treating physician's judgement.<br>* Other names: StemRegenin-1 cultured umbilical cord blood;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutrophil Recovery | Percentage of patients with neutrophil recovery | Day 14 after transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Graft Failure | Percentage of patients with secondary graft failure | Day 100 after transplantation | 
| Platelet Recovery | Percentage of patients with platelet recovery | Day 100 after transplantation | 
| Transplant-Related Mortality |  | 6 months after transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, ALL, MDS