Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3) (ZUMA-2)

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Relapsed/Refractory Mantle Cell Lymphoma

Treatments: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Brexucabtagene autoleucel

Study type: Interventional

Funder types: Industry

Identifiers

NCT04880434

2023-506641-35 (Other Identifier)

2015-005008-27 (EudraCT Number)

KTE-C19-102 (Cohort 3)

Details and patient eligibility

About

The goal of this clinical study is to test how well the study drug, brexucabtagene autoleucel (KTE-X19), works in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL) who have not previously received Bruton's tyrosine kinase inhibitor (BTKi).

Full description

Study KTE-C19-102 (NCT02601313) enrolled participants with r/r MCL who had been treated with up to 5 prior regimens, including a BTKi, in Cohorts 1 and 2. To fulfill an FDA postmarketing requirement, Cohort 3 is added to the study. Cohort 3 includes participants with r/r MCL who have been treated with up to five prior regimens but have not received prior therapy with a BTKi.

The final analysis for Cohorts 1 and 2 has been completed. Data for Cohort 3 are analyzed separately. Therefore, this separate registration is only for Cohort 3.

After the end of KTE-C19-102, subjects who received an infusion of anti-CD19 CAR T cells will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968 (NCT05041309).

Enrollment: 95 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Up to 5 prior regimens for mantle cell lymphoma (MCL). Prior therapy must have included anthracycline- or bendamustine-containing chemotherapy and anti-cluster of differentiation 20 (CD20) monoclonal antibody therapy. Individuals must not have received prior therapy with a Bruton's tyrosine kinase inhibitor (BTKi).
• At least 1 measurable lesion
• Platelet count ≥ 75,000/μL
• Creatinine clearance (as estimated by Cockcroft Gault) ≥ to 60 cc/min
• Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA), and no clinically significant electrocardiogram (ECG) findings
• Baseline oxygen saturation > 92% on room air

Key Exclusion Criteria:

• Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAG positive) or anti-hepatitis C virus (HCV) positive. Individuals with a history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing
• History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with central nervous system (CNS) involvement
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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95 participants in 1 patient group

Brexucabtagene autoleucel (KTE-X19)

Experimental group

Description:

Participants with relapsed or refractory (r/r) mantle cell lymphoma (MCL) who have been treated with up to 5 prior regimens but have not received prior therapy with a Bruton's tyrosine kinase inhibitor (BTKi) will receive the following treatment during the study: * A conditioning chemotherapy regimen of fludarabine 30 mg/m\^2/day and cyclophosphamide 500 mg/m\^2/day for 3 days (Day -5 to Day -3). * A single infusion of brexucabtagene autoleucel at a target dose of 2×10\^6 anti-cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) transduced autologous T cells/kg, with a maximum flat dose of 2 x 10\^8 anti-CD19 CAR T cells for participants \> 100 kg on Day 0.

Treatment:

Biological: Brexucabtagene autoleucel

Drug: Cyclophosphamide

Drug: Fludarabine