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

Phase 3TerminatedNCT03699475

Bellicum Pharmaceuticals1 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemia Myelodysplastic Syndromes

Interventions

rivogenlecleucelBIOLOGICAL

Biological: T cells transduced with caspase 9 safety switch

rimiducidDRUG

administered to inactivate rivogenlecleucel in the event of GVHD

CyclophosphamideDRUG

GVHD prophylaxis

Eligibility

Sex: ALLMin age: 12 YearsMax age: 70 Years

Medical Language ↔ Plain English

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)

Locations (2)

TriStar Bone Marrow Transplant, LLC

Nashville, Tennessee, United States

Methodist Healthcare System of San Antonio Clinical Trials Office

San Antonio, Texas, United States

Outcomes

Primary Outcomes

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)

Time frame: 100 days

Data from ClinicalTrials.gov

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