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

Acute Myeloid Leukemia Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03699475
• Other study ID #: BPX501-301A
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: December 27, 2018
• Est. completion date: July 23, 2019

Study information

• Verified date: September 2023
• Source: Bellicum Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: July 23, 2019
• Est. primary completion date: July 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 70 Years

Eligibility

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 ßHCG 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)

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Myelodysplastic Syndromes

Intervention

Biological:
• rivogenlecleucel
Biological: T cells transduced with caspase 9 safety switch

Drug:
• rimiducid
administered to inactivate rivogenlecleucel in the event of GVHD
• Cyclophosphamide
GVHD prophylaxis

Procedure:
• haplo-HSCT
treatment for disease

Locations

Country	Name	City	State
United States	TriStar Bone Marrow Transplant, LLC	Nashville	Tennessee
United States	Methodist Healthcare System of San Antonio Clinical Trials Office	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Bellicum Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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