Clinical trial NCT02765997: StemRegenin-1 Expanded vs Unexpanded UCB for High Risk Heme Malignancies
Official title: Single-Center, Open Label, Randomized Trial Comparing StemRegenin-1 Expanded Versus Unmanipulated Umbilical Cord Blood Transplantation In Patients With High-Risk Malignancy
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Acute Myeloid Leukemia
Acute Lymphocytic Leukemia
Chronic Myelogenous Leukemia
Myelodysplasia
Keywords: AML
ALL
MDS
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2016-05-09
Enrollment: 0
Sex: ALL
Minimum age (years): 2
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Neutrophil Recovery
timeFrame: Day 14 after transplantation
Secondary outcomes:
measure: Secondary Graft Failure
timeFrame: Day 100 after transplantation
measure: Platelet Recovery
timeFrame: Day 100 after transplantation
measure: Transplant-Related Mortality
timeFrame: 6 months after transplantation
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota Cancer Center
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: John Wagner, MD
role: PRINCIPAL_INVESTIGATOR
References: