Clinical Trials /

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

NCT03699475

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Acute Myeloid Leukemia with Myelodysplasia-Related Changes
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Study of Haplo-HSCT + BPX-501 vs Haplo-HSCT + Post Transplant Cyclophosphamide in Patients With AML or MDS
  • Official Title: Randomized Phase 2/3 Study of αβ T-Cell-Depleted, Related Haploidentical Hematopoietic Stem Cell Transplant Plus BPX 501 T-Cell Infusion vs Haplo-HSCT Plus Post Transplant Cyclophosphamide in Patients With AML or MDS

Clinical Trial IDs

  • ORG STUDY ID: BPX501-301A
  • NCT ID: NCT03699475

Conditions

  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
rivogenlecleucel & rimiducidBPX-501 T cellsA:HSCT plus rivogenlecleucel & rimiducid
rimiducidAP1903A:HSCT plus rivogenlecleucel & rimiducid
CyclophosphamideCytoxanB: HSCT followed by cyclophosphamide

Purpose

This study compares the safety and effectiveness of giving rivogenlecleucel (BPX501 T cells) to patients with AML or MDS post haploidentical hematopoietic stem cell transplant.

Detailed Description

      Participants will undergo αβ T cell and CD19+ B cell depleted 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: 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.
    

Trial Arms

NameTypeDescriptionInterventions
A:HSCT plus rivogenlecleucel & rimiducidExperimentalαβ 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
  • rivogenlecleucel & rimiducid
  • rimiducid
B: HSCT followed by cyclophosphamideActive Comparatorhaploidentical stem cell transplantation followed by cyclophosphamide post-transplant
  • Cyclophosphamide

Eligibility Criteria

        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 Recommendations (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 1 MDS patients who failed a hypomethylating agent

        Deemed eligible (by investigator) for allogeneic stem cell transplantation

        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

          -  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)
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival
Time Frame:3 years
Safety Issue:
Description:Time from randomization to death due to any cause

Secondary Outcome Measures

Measure:Graft-versus host disease and relapse-free survival (GRFS)
Time Frame:3 years
Safety Issue:
Description:Time from randomization until Grade 3-4 acute GvHD; chronic GvHD requiring systemic immunosuppression; disease relapse or death, whichever comes first
Measure:Relapse free survival (RFS)
Time Frame:3 years
Safety Issue:
Description:The Andersen-Gill model will be used to evaluate the incidence of relapse-free survival
Measure:Non-relapse mortality (NRM)
Time Frame:3 years
Safety Issue:
Description:The Andersen-Gill model will be used to evaluate the incidence of NRM
Measure:Time to resolution of GVHD after administration of rimiducid
Time Frame:3 years
Safety Issue:
Description: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

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Bellicum Pharmaceuticals

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