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

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

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.

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.

      1. Ph+ ALL, or
      2. MLL rearrangement with slow early response at Day 14, or
      3. Hypodiploidy (< 44 chromosomes or DNA index < 0.81), or
      4. End of induction M3 bone marrow, or
      5. 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.