stemregenin-1 expanded vs unexpanded ucb for high risk heme malignancies

Conditions: Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Myelodysplasia

Summary: 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.


Eligibility criteria:
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.

Keywords: aml all mds