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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Acute Myeloid Leukemia, Myelodysplastic Syndromes

Intervention / Treatment
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* Biological: rivogenlecleucel
* Drug: rimiducid
* Drug: Cyclophosphamide
* Procedure: haplo-HSCT


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: single-arm Phase II: 3 x 10E6 BPX-501 cell/kg<br>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 | Biological: rivogenlecleucel<br>* Biological: T cells transduced with caspase 9 safety switch<br>* Other names: BPX-501 T cells;Drug: rimiducid<br>* administered to inactivate rivogenlecleucel in the event of GVHD<br>* Other names: AP1903;Procedure: haplo-HSCT<br>* treatment for disease<br>|
| Experimental: phase 3 Arm A: Dose Determined in phase 2 group (never completed)<br>αβ T cell and CD19+ B cell-depleted, related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) plus rivogenlecleucel | Biological: rivogenlecleucel<br>* Biological: T cells transduced with caspase 9 safety switch<br>* Other names: BPX-501 T cells;Drug: rimiducid<br>* administered to inactivate rivogenlecleucel in the event of GVHD<br>* Other names: AP1903;Procedure: haplo-HSCT<br>* treatment for disease<br>|
| Active Comparator: phase 3 Arm B: dose determined in the phase 2 group (never completed)<br>haplo-HSCT followed by post-transplant cyclophosphamide (PTCy) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) | Drug: Cyclophosphamide<br>* GVHD prophylaxis<br>* Other names: Cytoxan;Procedure: haplo-HSCT<br>* treatment for disease<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |