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

Phase 2

Terminated

Conditions: Myelodysplastic Syndromes
Acute Myeloid Leukemia

Interventions: Biological: rivogenlecleucel
Drug: Cyclophosphamide
Drug: rimiducid
Procedure: haplo-HSCT

Registration Number: NCT03699475

Lead Sponsor: Bellicum Pharmaceuticals

Brief 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.

Detailed 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 & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
phase 3 Arm A: Dose Determined in phase 2 group (never completed)	rimiducid	αβ T cell and CD19+ B cell-depleted, related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) plus rivogenlecleucel
phase 3 Arm B: dose determined in the phase 2 group (never completed)	haplo-HSCT	haplo-HSCT followed by post-transplant cyclophosphamide (PTCy) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)
phase 3 Arm A: Dose Determined in phase 2 group (never completed)	haplo-HSCT	αβ T cell and CD19+ B cell-depleted, related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) plus rivogenlecleucel
single-arm Phase II: 3 x 10E6 BPX-501 cell/kg	rivogenlecleucel	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
single-arm Phase II: 3 x 10E6 BPX-501 cell/kg	rimiducid	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
phase 3 Arm A: Dose Determined in phase 2 group (never completed)	rivogenlecleucel	αβ T cell and CD19+ B cell-depleted, related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) plus rivogenlecleucel
single-arm Phase II: 3 x 10E6 BPX-501 cell/kg	haplo-HSCT	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
phase 3 Arm B: dose determined in the phase 2 group (never completed)	Cyclophosphamide	haplo-HSCT followed by post-transplant cyclophosphamide (PTCy) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

Primary Outcome Measures

Name	Time	Method
Number of Subjects Experiencing 3 or More Dose Limiting Toxicities [Phase 2] Within a 100-day DLT Window After Receiving BPX-501	100 days	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)

Secondary Outcome Measures

Name	Time	Method

Trial Locations

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