Study of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Participants With Relapsed/Refractory Follicular Lymphoma (ZUMA-22)

Gilead Sciences

Status and phase: Active, not recruiting; Phase 3

Conditions: Relapsed/Refractory Follicular Lymphoma

Treatments: Drug: Cyclophosphamide; Drug: Vincristine; Drug: Rituximab; Drug: Doxorubicin; Drug: Fludarabine; Drug: Lenalidomide; Drug: Prednisone; Biological: Axicabtagene Ciloleucel; Drug: Bendamustine

Study type: Interventional

Funder types: Industry

Identifiers

NCT05371093

2024-511594-30 (Other Identifier)

2021-003260-28 (EudraCT Number)

KT-US-473-0133

Details and patient eligibility

About

The goal of this clinical study is test how well the study drug, axicabtagene ciloleucel, works in participants with relapsed/refractory follicular lymphoma

Full description

Five years after the last study participant is randomized, participants who have received axicabtagene ciloleucel will transition to a separate Long-term Follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.

Enrollment: 230 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Histologically-confirmed follicular lymphoma (FL) (Grade 1, 2, or 3a)
• Relapsed/refractory (R/r) disease after first-line chemoimmunotherapy and high-risk disease with relapse or progression within 24 months of the initial course of chemoimmunotherapy (ie, POD24), Or r/r disease after ≥ 2 prior systemic lines of therapy
• Clinical indication for treatment.
• At least 1 measurable lesion per the Lugano Classification {Cheson 2014}
• Adequate renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria:

• Presence of large B cell lymphoma or transformed FL
• Small lymphocytic lymphoma
• Lymphoplasmacytic lymphoma
• Full-thickness involvement of the gastric wall by lymphoma
• FL Grade 3b
• Prior CD19-targeted therapy
• Prior CAR therapy or other genetically modified T-cell therapy
• Uncontrolled fungal, bacterial, viral, or other infection
• Active Infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus
• History or presence of a clincially significant central nervous system (CNS) disorder.
• History of autoimmune disease
• Known history or CNS lymphoma involvement
• Cardiac lymphoma involvement
• History of clinically significant cardiac disease 6 months before randomization
• Neuropathy greater than grade 2
• Females who are pregnant or breastfeeding
• Individuals of both genders who are not willing to practice birth control
• Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, G/J-tube, pleural/peritoneal/pericardial catheter, or Ommaya reservoirs). Dedicated central venous access catheters such as Port-a-Cath or Hickman catheter are permitted.

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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230 participants in 2 patient groups

Axicabtagene Ciloleucel

Experimental group

Description:

Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepleting chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells will be administered.

Treatment:

Biological: Axicabtagene Ciloleucel

Drug: Fludarabine

Drug: Cyclophosphamide

Standard of Care Therapy

Active Comparator group

Description:

Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus lenalidomide (R\^2) for 12 cycles (28-day cycle) * Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m\^2 on Day 1, Day 8, Day 15, and Day 22 * Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1 * Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21 * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle) * rituximab 375 mg/m\^2 on Day 1 * cyclophosphamide 750 mg/m\^2 on Day 1 * doxorubicin 50 mg/m\^2 on Day 1 * vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * prednisone 40 mg/m\^2 on Day 1 through Day 5 * Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle) * rituximab 375 mg/m\^2 on Day 1 * bendamustine 90 mg/m\^2 on Day 1 and Day 2

Treatment:

Drug: Bendamustine

Drug: Prednisone

Drug: Lenalidomide

Drug: Doxorubicin

Drug: Rituximab

Drug: Vincristine

Drug: Cyclophosphamide