Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Refractory Large B-cell Lymphoma

Treatments: Biological: Axicabtagene Ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Rituximab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04002401

KT-US-471-0114

2019-004803-11 (EudraCT Number)

Details and patient eligibility

About

The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.

Full description

Following at least 24 months of assessments after axicabtagene ciloleucel infusion, participants will be asked to rollover to a separate long-term follow-up study (Study KT-US-982-5968). Participants will complete the remainder of the 15-year follow-up assessments in the KT-US-982-5968 study.

Enrollment: 27 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Histologically confirmed large B-cell lymphoma

• Chemotherapy-refractory disease, defined as one or more of the following:

  • No response to first-line therapy (primary refractory disease)
  • No response to second or greater lines of therapy OR
  • Refractory after autologous stem cell transplant (ASCT)

• At least 1 measureable lesion according to the Lugano Classification (Cheson 2014).

• Individuals must have received adequate prior therapy, including at a minimum:

  • Anti-CD20 monoclonal antibody
  • An anthracycline-containing chemotherapy regimen

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Adequate renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria:

• Known CD19 negative or CD20 negative tumor
• History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL)
• Prior CAR therapy or other genetically modified T-cell therapy
• Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
• Prior CD19 targeted therapy
• Clinically significant infection or cardiopulmonary disease
• Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed)
• History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases
• History of autoimmune disease
• History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months

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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27 participants in 1 patient group

Axicabtagene Ciloleucel and Rituximab Combination

Experimental group

Description:

Participants will receive rituximab 375 mg/m\^2, once on Day -5 along with conditioning chemotherapy (fludarabine 30 mg/m\^2 over 30 minutes and cyclophosphamide 500 mg/m\^2 over 60 minutes) once on Days -5 to -3, followed by axicabtagene ciloleucel 2 x 10\^6 anti-cluster of differentiate 19 (CD19) chimeric antigen receptor (CAR) T cells/kg once on Day 0 and additional rituximab 375 mg/m\^2 of 5 doses, once every 28 days starting from Day 21 up to Day 133.

Treatment:

Drug: Fludarabine

Biological: Axicabtagene Ciloleucel

Drug: Rituximab

Drug: Cyclophosphamide