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.

Study Overview

• Status: Withdrawn
• Conditions: Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Chronic Myelogenous Leukemia; Myelodysplasia
• Intervention / Treatment: Biological: Unmanipulated UCB; Biological: SR-1 UCB

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 35 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Unmanipulated UCB; Subjects will receive unmanipulated umbilical cord blood transplantation after a myeloablative CY/FLU/TBI conditioning.	Biological: Unmanipulated UCB; 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.; Other Names: Unmanipulated Umbilical Cord Blood
Experimental: StemRegenin-1 UCB; Subjects will receive StemRegenin-1 (SR-1) cultured umbilical cord blood transplantation after a myeloablative CY/FLU/TBI conditioning.	Biological: SR-1 UCB; 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.; Other Names: StemRegenin-1 cultured umbilical cord blood

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: John Wagner, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2017
• Primary Completion (Anticipated): June 1, 2020
• Study Completion (Anticipated): June 1, 2022

Study Registration Dates

• First Submitted: May 5, 2016
• First Submitted That Met QC Criteria: May 5, 2016
• First Posted (Estimate): May 9, 2016

Study Record Updates

• Last Update Posted (Actual): December 5, 2017
• Last Update Submitted That Met QC Criteria: December 3, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: AML; ALL; MDS
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia, Lymphoid; Leukemia; Leukemia, Myeloid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Other Study ID Numbers: 2016LS006; MT2016-01 (Other Identifier: University of Minnesota Masonic Cancer Center)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No