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

NCT04002401 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: KT-US-471-01142019-004803-11
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Refractory Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate Per the International Working Group (IWG) Lugano Classification as Determined by Study Investigators

  CR rate is defined as the incidence of a CR per the IWG Lugano Classification as determined by study investigators. CR rate: percentage of participants with CR \[complete metabolic response (CMR); complete radiological response (CRR)\]. CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake \> mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology. 95% confidence interval (CI) was calculated by Clopper-Pearson method.

  First infusion date up to maximum duration of 32.7 months

Secondary Outcomes (10)

• Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)

  First infusion date up to maximum duration of 27 months

• Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value

  First infusion date up to maximum duration of 27 months

• Objective Response Rate (ORR) Per the IWG Lugano Classification as Determined by Study Investigators

  First infusion date up to maximum duration of 32.7 months

• Duration of Response (DOR) Per the IWG Lugano Classification as Determined by Study Investigators

  From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (up to approximately 32.7 months)

• Progression-Free Survival (PFS) Per the IWG Lugano Classification as Determined by Study Investigators

  First infusion date up to disease progression or death regardless of cause (up to approximately 32.7 months)

Study Arms (1)

Axicabtagene Ciloleucel and Rituximab Combination

EXPERIMENTAL

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.

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

Interventions

Axicabtagene Ciloleucel BIOLOGICAL

A single infusion of CAR-transduced autologous T cells administered intravenously

Also known as: Yescarta®

Axicabtagene Ciloleucel and Rituximab Combination

Rituximab DRUG

Administered intravenously

Also known as: RITUXAN®

Axicabtagene Ciloleucel and Rituximab Combination

Fludarabine DRUG

Administered according to package insert

Axicabtagene Ciloleucel and Rituximab Combination

Cyclophosphamide DRUG

Administered according to package insert

Axicabtagene Ciloleucel and Rituximab Combination

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Kite, A Gilead Company: lead

Study Sites (14)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

City of Hope National Medical Center

Duarte, California, 91010-3012, United States

Location

Stanford Cancer Institute

Palo Alto, California, 94305, United States

Location

UCLA Hematology/Oncology

Santa Monica, California, 90404, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Columbia University Medical Center, New York Presbyterian Hospital

New York, New York, 10032, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

St. David's South Austin Medical Center

Austin, Texas, 78704, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Related Publications (2)

• Strati P, Leslie L, Shiraz P, Budde LE, Oluwole OO, Ulrickson M, Ramakrishnan A, Zhang T, Sun J, Milletti F, Kanska J, Shen R, Neumann F, Xu H, Patel K. Axicabtagene ciloleucel in combination with rituximab for refractory large B cell lymphoma: the phase 2, single-arm ZUMA-14 trial. Nat Cancer. 2026 Jan 5. doi: 10.1038/s43018-025-01102-1. Online ahead of print.

  PMID: 41492094 DERIVED

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

  PMID: 34515338 DERIVED

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

axicabtagene ciloleucel; Rituximab; fludarabine; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Medical Information
• Organization: Kite, A Gilead Company

medinfo@kitepharma.com

844-454-5483 (1-844-454-KITE)

Study Officials

• Kite Study Director

  Kite, A Gilead Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2019
• First Posted: June 28, 2019
• Study Start: November 5, 2019
• Primary Completion: January 30, 2023
• Study Completion: January 30, 2023
• Last Updated: February 20, 2024
• Results First Posted: February 20, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

US (14)