A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (ZUMA-5)

A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL)

This study will enroll approximately 160 adult participants who have relapsed or refractory (r/r) iNHL to be infused with the study treatment, axicabtagene ciloleucel, to see if their disease responds to this experimental product and if this product is safe. Axicabtagene ciloleucel is made from the participants own white blood cells which are genetically modified and grown to fight cancer. An objective response rate of 70% is targeted.

Study Overview

• Status: Active, not recruiting
• Conditions: Follicular Lymphoma; Marginal Zone Lymphoma; Indolent Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: axicabtagene ciloleucel

Detailed Description

All enrolled participants will be screened for eligibility then will undergo leukapheresis to collect white blood cells for manufacturing. In preparation for the infusion with axicabtagene ciloleucel, participants will undergo conditioning chemotherapy with cyclophosphamide and fludarabine for 3 days to help the study treatment be effective. After the product is manufactured and conditioning chemotherapy period is complete, participants will be infused with axicabtagene ciloleucel and then monitored in a hospital for a minimum of 7 days. After completing at least 60 months (FL participants) or at least 24 months (MZL participants) of assessments in this study since the initial axicabtagene ciloleucel infusion and after agreement by the Sponsor, participants will transition to a long-term follow-up (LTFU) study, KT-US-982-5968 where they will complete the remainder of the 15 year follow-up assessments.

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Lille, France, 59037
    • Centre Hospitalier Regional Universitaire de Lille
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Banner MD Anderson Cancer Center
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown Lombardi Comprehensive Cancer Center
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Hospital and Clinics
    • Tampa, Florida, United States, 33612
      • H Lee Moffitt Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center - John Theurer Cancer Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center (URMC)
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Ohio State University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Individual has [follicular lymphoma or marginal zone lymphoma that has progressed after at least 2 lines of treatment with combination chemoimmunotherapy] (e.g. R-bendamustine, R-CHOP).
2. Individual has [measurable disease].
3. Individual has no known presence or history of central nervous system (CNS) involvement by lymphoma.
4. If individual is on conventional systemic therapy or systemic inhibitory/stimulatory immune checkpoint therapy, individual is able to stop conventional therapy 2 weeks or 5 half-lives, whichever is shorter, or immune checkpoint therapy 3 half-lives prior to planned leukapheresis.
5. Individual has Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and adequate renal, hepatic, pulmonary, and cardiac function
6. Individual is not pregnant or breastfeeding (female individuals only) and is willing to use birth control from the time of consent through 12 months following chimeric antigen receptor (CAR) T cell infusion (both male and female individuals).

Key Exclusion Criteria:

1. Transformed follicular lymphoma (FL) or marginal zone lymphoma (MZL)
2. Small lymphocytic lymphoma
3. Histological Grade 3b FL
4. Individual will have undergone autologous transplant within 6 weeks of planned leukapheresis or has undergone allogeneic transplant.
5. Individual has evidence of involvement of the heart by lymphoma or requirement for urgent therapy due to ongoing or impending oncologic emergency (e.g. mass effect, tumor lysis syndrome, etc.)

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: axicabtagene ciloleucel; Participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide, followed by a single infusion of CAR transduced autologous T cells.	Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Biological: axicabtagene ciloleucel; A single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered intravenously.; Other Names: Yescarta®; Axicab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate per central read	Complete response (CR) + partial response (PR) per the Lugano Classiciation (Cheson et al, 2014).	Up to 15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Treatment-Emergent Adverse Events		Up to 15 years
CR Rate per central read	CRR is defined as the incidence of CR as best response to treatment by the Lugano Classification (Cheson et al, 2014)	Up to 15 years
DOR	DOR is defined only for subjects who experience an objective response and is the time from the first objective response to disease progression per (Cheson et al, 2014) or disease-related death, whichever comes first.	Up to 15 years
PFS	PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per (Cheson et al, 2014) or death from any cause.	Up to 15 years
Overall Survival (OS)	OS is defined as the time from KTE-C19 infusion to the date of death.	Up to 15 years
Levels of anti-CD19 CAR T cells in blood		At enrollment, Day 7, Week 2, Week 4, Month 3, Month 6, Month 12, Month 18, Month 24, annually up to year 5.
Levels of cytokines in serum		At enrollment, prior to axicabtagene ciloleucel infusion on Day 0, Day 3, Day 7, Week 2, Week 4
Percentage of Participants experiencing anti-axicabtagene ciloleucel antibodies		At enrollment, Week 4, Month 3, every 3 months up to Month 12
Percentage of Participants Experiencing clinically significant changes in lab values		Up to 5 years
Time to next Therapy	Time from axi-cel infusion date to the start of the subsequent new lymphoma therapy or death from any cause.	Up to 15 years
Objective response rate among participants with 3 or more lines of prior therapy	Complete response (CR) + partial response (PR) per the Lugano Classiciation (Cheson et al, 2014) for participants with 3 or more lines of prior therapy.	Up to 15 years
Complete response rate among those participants with 3 or more lines of prior therapy	Complete response rate is defined as the incidence of CR as best response to treatment by the Lugano Classification (Cheson et al, 2014) for participants with 3 or more lines of prior therapy.	Up to 15 years
Objective Response Rate as Determined by the Investigator Read	ORR per investigator read is defined as the incidence of a CR or a PR by the Lugano Classification.	Up to 15 years
Best Objective Response per Central Read or Investigator Read	Best objective response is defined as the incidence of CR, PR, stable disease (SD), PD, or non-evaluable (NE) as best response to treatment by the Lugano Classification	Up to 15 years

Collaborators and Investigators

• Sponsor: Kite, A Gilead Company
• Investigators: Study Director: Kite Study Director, Kite, A Gilead Company

Publications and helpful links

General Publications

• Ghione P, Palomba ML, Patel AR, Bobillo S, Deighton K, Jacobson CA, Nahas M, Hatswell AJ, Jung AS, Kanters S, Snider JT, Neelapu SS, Ribeiro MT, Brookhart MA, Ghesquieres H, Radford J, Gribben JG. Comparative effectiveness of ZUMA-5 (axi-cel) vs SCHOLAR-5 external control in relapsed/refractory follicular lymphoma. Blood. 2022 Aug 25;140(8):851-860. doi: 10.1182/blood.2021014375.
• Jacobson CA, Chavez JC, Sehgal AR, William BM, Munoz J, Salles G, Munshi PN, Casulo C, Maloney DG, de Vos S, Reshef R, Leslie LA, Yakoub-Agha I, Oluwole OO, Fung HCH, Rosenblatt J, Rossi JM, Goyal L, Plaks V, Yang Y, Vezan R, Avanzi MP, Neelapu SS. Axicabtagene ciloleucel in relapsed or refractory indolent non-Hodgkin lymphoma (ZUMA-5): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2022 Jan;23(1):91-103. doi: 10.1016/S1470-2045(21)00591-X. Epub 2021 Dec 8.

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2017
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: April 3, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (Actual): April 7, 2017

Study Record Updates

• Last Update Posted (Actual): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, B-Cell; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell, Marginal Zone; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Cyclophosphamide; Fludarabine; Axicabtagene ciloleucel
• Other Study ID Numbers: KTE-C19-105; 2017-001912-13 (EudraCT Number); 2023-505169-10 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No