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

Primary Purpose

Acute Myeloid Leukemia, Myelodysplastic Syndromes

Status

Terminated

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

rivogenlecleucel

rimiducid

Cyclophosphamide

haplo-HSCT

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia

Eligibility Criteria

12 Years - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

TriStar Bone Marrow Transplant, LLC
Methodist Healthcare System of San Antonio Clinical Trials Office

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

single-arm Phase II: 3 x 10E6 BPX-501 cell/kg

phase 3 Arm A: Dose Determined in phase 2 group (never completed)

phase 3 Arm B: dose determined in the phase 2 group (never completed)

Arm Description

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

αβ T cell and CD19+ B cell-depleted, related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) plus rivogenlecleucel

haplo-HSCT followed by post-transplant cyclophosphamide (PTCy) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Full Information

NCT ID

NCT03699475

First Posted

October 5, 2018

Last Updated

September 22, 2023

Sponsor

Bellicum Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT03699475

Brief Title

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

Acronym

THRIVE

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Terminated

Why Stopped

Funding, portfolio re-prioritization

Study Start Date

December 27, 2018 (Actual)

Primary Completion Date

July 23, 2019 (Actual)

Study Completion Date

July 23, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bellicum Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Myeloid Leukemia, Myelodysplastic Syndromes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

single-arm Phase II: 3 x 10E6 BPX-501 cell/kg

Arm Type

Experimental

Arm Description

Arm Title

phase 3 Arm A: Dose Determined in phase 2 group (never completed)

Arm Type

Experimental

Arm Description

αβ T cell and CD19+ B cell-depleted, related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) plus rivogenlecleucel

Arm Title

phase 3 Arm B: dose determined in the phase 2 group (never completed)

Arm Type

Active Comparator

Arm Description

haplo-HSCT followed by post-transplant cyclophosphamide (PTCy) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

Intervention Type

Biological

Intervention Name(s)

rivogenlecleucel

Other Intervention Name(s)

BPX-501 T cells

Intervention Description

Biological: T cells transduced with caspase 9 safety switch

Intervention Type

Drug

Intervention Name(s)

rimiducid

Other Intervention Name(s)

AP1903

Intervention Description

administered to inactivate rivogenlecleucel in the event of GVHD

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan

Intervention Description

GVHD prophylaxis

Intervention Type

Procedure

Intervention Name(s)

haplo-HSCT

Intervention Description

treatment for disease

Primary Outcome Measure Information:

Title

Number of Subjects Experiencing 3 or More Dose Limiting Toxicities [Phase 2] Within a 100-day DLT Window After Receiving BPX-501

Description

Time Frame

100 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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 (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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bellicum Pharmaceuticals

Organizational Affiliation

Bellicum Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

TriStar Bone Marrow Transplant, LLC

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37203

Country

United States

Facility Name

Methodist Healthcare System of San Antonio Clinical Trials Office

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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