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

NCT03699475 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: BPX501-301A
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 2

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.

Conditions

Acute Myeloid Leukemia; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (3)

single-arm Phase II: 3 x 10E6 BPX-501 cell/kg

EXPERIMENTAL

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; Drug: rimiducid; Procedure: haplo-HSCT

phase 3 Arm A: Dose Determined in phase 2 group (never completed)

EXPERIMENTAL

αβ T cell and CD19+ B cell-depleted, related haploidentical hematopoietic stem cell transplantation (haplo-HSCT) plus rivogenlecleucel

Biological: rivogenlecleucel; Drug: rimiducid; Procedure: haplo-HSCT

phase 3 Arm B: dose determined in the phase 2 group (never completed)

ACTIVE COMPARATOR

haplo-HSCT followed by post-transplant cyclophosphamide (PTCy) in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS)

Drug: Cyclophosphamide; Procedure: haplo-HSCT

Interventions

rivogenlecleucel BIOLOGICAL

Biological: T cells transduced with caspase 9 safety switch

Also known as: BPX-501 T cells

phase 3 Arm A: Dose Determined in phase 2 group (never completed); single-arm Phase II: 3 x 10E6 BPX-501 cell/kg

rimiducid DRUG

administered to inactivate rivogenlecleucel in the event of GVHD

Also known as: AP1903

phase 3 Arm A: Dose Determined in phase 2 group (never completed); single-arm Phase II: 3 x 10E6 BPX-501 cell/kg

Cyclophosphamide DRUG

GVHD prophylaxis

Also known as: Cytoxan

phase 3 Arm B: dose determined in the phase 2 group (never completed)

haplo-HSCT PROCEDURE

treatment for disease

phase 3 Arm A: Dose Determined in phase 2 group (never completed); phase 3 Arm B: dose determined in the phase 2 group (never completed); single-arm Phase II: 3 x 10E6 BPX-501 cell/kg

Eligibility Criteria

• Age: 12 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• Bellicum Pharmaceuticals: lead

Study Sites (2)

TriStar Bone Marrow Transplant, LLC

Nashville, Tennessee, 37203, United States

Location

Methodist Healthcare System of San Antonio Clinical Trials Office

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

AP 1903 reagent; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Bellicum

clinicaltrials@bellicum.com

(832) 384-1100

Study Officials

• Bellicum Pharmaceuticals

  Bellicum Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: October 5, 2018
• First Posted: October 9, 2018
• Study Start: December 27, 2018
• Primary Completion: July 23, 2019
• Study Completion: July 23, 2019
• Last Updated: September 29, 2023
• Results First Posted: September 1, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)