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

University of Minnesota (UMN)

Status and phase

Withdrawn

Phase 2

Conditions

Acute Lymphocytic Leukemia

Myelodysplasia

Chronic Myelogenous Leukemia

Acute Myeloid Leukemia

Treatments

Biological: SR-1 UCB

Biological: Unmanipulated UCB

Study type

Interventional

Funder types

Other

Identifiers

NCT02765997

MT2016-01 (Other Identifier)

2016LS006

Details and patient eligibility

About

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.

Sex

All

Ages

2 to 35 years old

Volunteers

No Healthy Volunteers

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.