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

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.

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.

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)