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THRIVE: Study of Haplo-HSCT + Rivogenlecleucel vs Haplo-HSCT + Post Transplant Cyclophosphamide in Patients With AML or MDS

Sponsor
Bellicum Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT03699475
Collaborator
(none)
1
Enrollment
2
Locations
2
Arms
6.8
Actual Duration (Months)
0.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study compares the safety and effectiveness of giving rivogenlecleucel (BPX-501 T cells) to patients with AML or MDS post haploidentical hematopoietic stem cell transplant compared to post-transplant cyclophosphamide.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Detailed Description

In the Phase 2 portion, participants will undergo αβ T cell and CD19+ B cell depleted haploidentical HSCT followed by an infusion of a fixed dose of rivogenlecleucel (BPX-501 T cells) per kg. These participants will be evaluated for prespecified dose limiting toxicities (DLTs) for a 100-day dose limiting toxicity window.

Following completion of the Phase 2 portion, participants will be enrolled and randomized to one of two treatment arms in the Phase 3 portion.

  • Arm A:αβ T-cell and CD19+ B-cell-depleted haplo-HSCT plus treatment with rivogenlecleucel

  • Arm B: haplo-HSCT plus post transplant cyclophosphamide

Pediatric patients ages 12-17 will also be included in US only.

Study Design

Study Type:
Interventional
Actual Enrollment :
1 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II/III Study of αβ T Cell-Depleted, Related, Haploidentical Hematopoietic Stem Cell Transplant (Haplo-HSCT) Plus Rivogenlecleucel vs. Haplo-HSCT Plus Post-Transplant Cyclophosphamide (PTCy) in Patients With AML or MDS
Actual Study Start Date :
Dec 27, 2018
Actual Primary Completion Date :
Jul 23, 2019
Actual Study Completion Date :
Jul 23, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: A: haplo-HSCT plus rivogenlecleucel

αβ T-cell and CD19+ B-cell-depleted haploidentical stem cell transplantation plus rivogenlecleucel Rimiducid will be administered to inactivate rivogenlecleucel in the event of GVHD not responsive to standard of care treatment

Biological: rivogenlecleucel
Biological: T cells transduced with caspase 9 safety switch
Other Names:
  • BPX-501 T cells

    • Drug: rimiducid
    administered to inactivate rivogenlecleucel in the event of GVHD
    Other Names:
  • AP1903

    • Procedure: haplo-HSCT
    treatment for disease
    Active Comparator: B: haplo-HSCT followed by cyclophosphamide

    haploidentical stem cell transplantation followed by cyclophosphamide post-transplant

    Drug: Cyclophosphamide
    GVHD prophylaxis
    Other Names:
  • Cytoxan

    • Procedure: haplo-HSCT
    treatment for disease

    Outcome Measures

    Primary Outcome Measures

    1. Maximum Allowable Dose/Schedule [Phase 2] [100 days]

      Determine the maximum allowable dose/schedule of rivogenlecleucel and the recommended Phase 3 dose of rivogenlecleucel

    2. Rimiducid Activity [Phase 2] [24 months]

      Assess the activity of Rimiducid in subjects who develop GVHD post rivogenlecleucel administration

    3. Overall survival [Phase 3] [3 years]

      Time from randomization to death due to any cause

    Secondary Outcome Measures

    1. Relapse free survival (RFS) [Phase 3] [3 years]

      Time from randomization to relapse or death from any cause

    2. Graft-versus host disease and relapse-free survival (GRFS) [Phase 3] [3 years]

      Time from randomization until Grade 3-4 acute GVHD; chronic GVHD requiring systemic immunosuppression; disease relapse or death, whichever comes first

    3. Non-relapse mortality (NRM) [Phase 3] [3 years]

      Time from randomization to death without relapse/disease progression

    4. Time to resolution of GVHD after administration of rimiducid [Phase 3] [3 years]

      Resolution of GVHD after administration of rimiducid is defined as complete response or improvement of at least one grade of acute GVHD in patients receiving 1-3 doses of rimiducid

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    Signed informed consent

    Meeting institutional criteria to undergo allogenic HSCT

    Age 18-70 y/o (12-70 y/o in US only)

    Patients with AML or MDS as defined below:

    AML Patients Patients with intermediate to adverse AML as defined by ELN (Dohner, 2017).

    • AML in first complete remission (CR1) with high-risk features defined as > 1 cycle of induction therapy required to achieve remission OR preceding MDS or myeloproliferative disease

    • AML in CR1 with intermediate-risk features

    • AML in second or subsequent complete response

    • AML with myelodysplasia-related changes (AML-MRC)

    • Therapy related AML in first or subsequent complete remission

    • De novo AML in second or subsequent complete remission

    MDS Patients

    • High or very-high risk MDS by IPSS-R classification

    • Intermediate risk or higher MDS patients who failed a hypomethylating agent

    Lack of suitable conventional donor (i.e. HLA 10/10 related or unrelated donor)

    At least a 5/10 genotypic identical haplotype match

    The donor and recipient must be identical, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1

    Patients with adequate organ function

    Eastern Cooperative Oncology Group (ECOG) performance status: 0-2

    Exclusion Criteria:

    • HLA 10/10 allele matched (HLA-A,-B,-C,-DRBl, and DQB1) related donor or unrelated donor

    • Autologous hematopoietic stem cell transplant ≤ 3 months before enrollment

    • Prior allogeneic transplantation

    • Active CNS involvement by malignant cells (less than 2 months from the conditioning)

    • Current uncontrolled clinically active bacterial, viral or fungal infection

    • Positive HIV serology or viral RNA

    • Pregnancy (positive serum or urine βHCG test) or breast-feeding

    • Fertile men or women unwilling to use effective forms of birth control or abstinence for a year after transplantation

    • Radiographic, histologic, or known history of cirrhosis

    • Overlapping MDS and myeloproliferative neoplasms (MPN) disease

    • Patients with acute promyelocytic leukemia (APL)

    • Known hypersensitivity to dimethyl sulfoxide (DMSO)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 TriStar Bone Marrow Transplant, LLC Nashville Tennessee United States 37203
    2 Methodist Healthcare System of San Antonio Clinical Trials Office San Antonio Texas United States 78229

    Sponsors and Collaborators

    • Bellicum Pharmaceuticals

    Investigators

    • Study Director: Bellicum Pharmaceuticals, Bellicum Pharmaceuticals, Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Bellicum Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03699475
    Other Study ID Numbers:
    • BPX501-301A
    First Posted:
    Oct 9, 2018
    Last Update Posted:
    Nov 16, 2020
    Last Verified:
    Nov 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Myelodysplastic Syndromes
    Cyclophosphamide

    Study Results

    No Results Posted as of Nov 16, 2020