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

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)