Study of Zola-cel (BMS-986353), in Participants With Autoimmune Cytopenia (Breakfree-AiCE)

Official title

A Phase 2, Multicenter, Open-Label Study of Zolacabtagene Autoleucel (BMS-986353), CD19-Targeted NEX-T CAR T Cells, in Participants With Chronic Immune Thrombocytopenia (cITP) and Autoimmune Hemolytic Anemia (AIHA)

Overview

The purpose of this study is to evaluate the safety and efficacy of Zola-cel (BMS-986353), in participants with chronic immune thrombocytopenia (cITP) and autoimmune hemolytic anemia (AIHA).

Interventions

• Biological BMS-986353
  Specified dose of specified days
• Drug Fludarabine Phosphate
  Specified dose of specified days
• Drug Cyclophosphamide
  Specified dose on specified days

Primary outcome measures

• Cohort 1 Part A: Number of participants with treatment-emergent adverse events (TEAEs) [Time frame: Up to approximately Month 36]
• Cohort 1 Part A: Number of participants with serious AEs (SAEs) [Time frame: Up to approximately Month 36]
• Cohort 1 Part A: Number of participants with AEs of special interest (AESI) [Time frame: Up to approximately Month 36]
• Cohort 1 Part A: Number of participants with clinically significant laboratory abnormalities [Time frame: Up to approximately Month 36]
• Cohort 1 Part B: Hematologic Complete Response (CR) [Time frame: Up to approximately Month 6]

Secondary outcome measures (12)

• Cohort 1 PART B: Hematologic Overall Response (OR) [Time frame: Up to approximately Month 6]
• Cohort 1 PART A and Cohort 2: Hematologic CR and OR [Time frame: Up to approximately Month 6]
• Cohort 1 PART B and Cohort 2: Number of participants with TEAEs [Time frame: Up to approximately Month 36]
• Cohort 1 PART B and Cohort 2: Number of participants with SAEs [Time frame: Up to approximately Month 36]
• Cohort 1 PART B and Cohort 2: Number of participants with AESIs [Time frame: Up to approximately Month 36]
• Cohort 1 PART B and Cohort 2: Number of participants with clinically significant laboratory abnormalities [Time frame: Up to approximately Month 36]
• Number of participants with Hematologic PR [Time frame: Up to approximately Month 6]
• Number of participants with Hematologic CR [Time frame: Up to approximately Month 36]
• Number of participants with Hematologic PR [Time frame: Up to approximately Month 36]
• Number of participants with Hematologic OR [Time frame: Up to approximately Month 36]
• Number of participants with Best Overall Response (BOR) [Time frame: Up to approximately Month 36]
• Number of participants with durable CR, PR and OR [Time frame: Up to approximately 12 months from Zola-cel infusion]

Eligibility criteria

Inclusion criteria

Inclusion Criteria for ITP

• Documented clinical diagnosis of chronic ITP (cITP) without other clinical manifestations of systemic autoimmune disease.
• Has relapsed after or is intolerant to corticosteroids (with or without intravenous immunoglobulin (IVIG) or anti-Rh0(D) Ig) AND has failed, relapsed after, or is intolerant to therapies with ≥ 2 mechanisms of action, with at least one being immunosuppressive or immunomodulatory.

Platelet count < 30 × 109/L. For participants on thrombopoietin receptor agonist (TPO-RA): platelet count < 50 × 109/L.

Inclusion Criteria for AIHA

• Documented clinical diagnosis of AIHA (including warm autoimmune hemolytic anemia (wAIHA), cold agglutinin disease (CAD), or mixed AIHA) without other clinical manifestations of systemic autoimmune disease.

o wAIHA and mixed warm and cold AIHA: Failed, relapsed after, or is intolerant to at least 2 prior lines of treatment with 2 mechanisms of action (not including corticosteroids or IVIG), one of which is an anti-CD20 monoclonal antibody unless there is a documented contraindication.

o CAD (all of the following must apply): Failed, relapsed after, or is intolerant to at least 2 prior lines of treatment with 2 mechanisms of action, one of which is an anti-CD20 monoclonal antibody with or without chemotherapy unless there is a documented contraindication.

• Hb <10 g/dL without red blood cell transfusion, or transfusion dependent
• Documented hemolysis

Exclusion criteria

Medical Conditions

• ITP or AIHA associated with: Evans syndrome, other systemic autoimmune disease or single organ autoimmune disease requiring systemic immunosuppressive therapy, hepatitis C virus, HIV, drug induced (eg, non-steroidal anti-inflammatory drug (NSAIDS), trimethoprim/sulfamethoxazole (TMP-SMX), anticonvulsants), surgical procedures, or hematologic malignancies.
• COVID-19 Vaccine-induced immune thrombotic thrombocytopenia
• Prior history of solid organ malignancies, unless the participant has been free of the disease for ≥ 2 years.

Laboratory Test Findings

• Peripheral blood ANC < 1.5 × 109/L or requiring G-CSF or GM-CSF support o ALT/AST: ITP: ALT/AST: > 3 × ULN AIHA: ALT > 3 ULN. AST up to 5 × ULN may be permitted. o Bilirubin: ITP: total bilirubin > 1.5 × ULN AIHA: direct bilirubin > 1.5 × ULN o International normalized ratio (INR) > 1.5 × ULN

Other protocol-defined inclusion/exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

• Local Institution - 101 — Boston
• Local Institution - 103 — Houston
• Local Institution - 102 — Seattle

Germany · 2 centers

• Local Institution - 301 — Magdeburg
• Local Institution - 302 — Erlangen

United Kingdom · 2 centers

• Local Institution - 401 — London
• Local Institution - 402 — Sheffield

Denmark · 1 center

• Local Institution - 201 — Odense

Identifiers

NCT: NCT07603557 · CA061-1040

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗