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

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia; Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Cyclophosphamide; Biological: rivogenlecleucel; Drug: rimiducid; Procedure: haplo-HSCT

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 Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2; Phase 3

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • TriStar Bone Marrow Transplant, LLC
  • Texas
    • San Antonio, Texas, United States, 78229
      • Methodist Healthcare System of San Antonio Clinical Trials Office

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: phase 3 Arm A: Dose Determined in phase 2 group (never completed); αβ T cell and CD19+ B cell-depleted, related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) plus rivogenlecleucel	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: phase 3 Arm B: dose determined in the phase 2 group (never completed); haplo-HSCT followed by post-transplant cyclophosphamide (PTCy) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)	Drug: Cyclophosphamide; GVHD prophylaxis; Other Names: Cytoxan; Procedure: haplo-HSCT; treatment for disease
Experimental: single-arm Phase II: 3 x 10E6 BPX-501 cell/kg; Determining the safety of maximum allowable Dose for BPX-501 starting at 3 x 10E6 cells/kg 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects Experiencing 3 or More Dose Limiting Toxicities [Phase 2] Within a 100-day DLT Window After Receiving BPX-501	If any of the following adverse events that occur within the DLT window they will be considered a DLT: Grade III or IV acute GVHD attributable to rivogenlecleucel and non-responsive to > 1 dose of rimiducid treatment (plus standard doses (at least 1 mg/kg) of methylprednisone or dose equivalent of other corticosteroids, and/or calcineurin inhibitor) within 14 days; Grade 3-4 neurologic events attributable to rivogenlecleucel; Death due to any cause other than underlying disease; Any CTCAE Grade 3-5 adverse events related to rivogenlecleucel (including allergic reactions, infusion reactions, and any other related adverse reactions whether expected or unexpected). in case 3 or more DLTs are observed with 3 x 10E6 dose, another cohort would have been enrolled to receive the 1 x 10E6 cell dose (never happened as study terminated early)	100 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse free survival (RFS) [Phase 3]	Time from randomization to relapse or death from any cause	3 years
Graft-versus host disease and relapse-free survival (GRFS) [Phase 3]	Time from randomization until Grade 3-4 acute GVHD; chronic GVHD requiring systemic immunosuppression; disease relapse or death, whichever comes first	3 years
Non-relapse mortality (NRM) [Phase 3]	Time from randomization to death without relapse/disease progression	3 years
Time to resolution of GVHD after administration of rimiducid [Phase 3]	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	3 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2018
• Primary Completion (Actual): July 23, 2019
• Study Completion (Actual): July 23, 2019

Study Registration Dates

• First Submitted: October 5, 2018
• First Submitted That Met QC Criteria: October 5, 2018
• First Posted (Actual): October 9, 2018

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Myelodysplastic Syndromes; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: BPX501-301A

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No