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

• ClinicalTrials.gov Identifier: NCT03105336
• Recruitment Status: Active, not recruiting
• First Posted: April 7, 2017
• Last Update Posted: February 26, 2024
• Sponsor: Kite, A Gilead Company
• Information provided by (Responsible Party): Gilead Sciences ( Kite, A Gilead Company )

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Follicular Lymphoma; Marginal Zone Lymphoma; Indolent Non-Hodgkin Lymphoma	Biological: axicabtagene ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 159 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL)
• Actual Study Start Date: June 20, 2017
• Estimated Primary Completion Date: January 2025
• Estimated Study Completion Date: January 2025

Arms and Interventions

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.	Biological: axicabtagene ciloleucel; A single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered intravenously.; Other Names: Axicab; Yescarta®; Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States, 85234

United States, California

USC Norris Comprehensive Cancer Center

Los Angeles, California, United States, 90033

University of California Los Angeles

Los Angeles, California, United States, 90095

United States, District of Columbia

Georgetown Lombardi Comprehensive Cancer Center

Washington, District of Columbia, United States, 20007

United States, Florida

University of Miami Hospital and Clinics

Miami, Florida, United States, 33136

H Lee Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Massachusetts

Dana Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, New Jersey

Hackensack University Medical Center - John Theurer Cancer Center

Hackensack, New Jersey, United States, 07601

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

University of Rochester Medical Center (URMC)

Rochester, New York, United States, 14642

United States, Ohio

Ohio State University Medical Center

Cleveland, Ohio, United States, 44106

United States, Pennsylvania

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States, 19111

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

Vanderbilt University Medical Center

Nashville, Tennessee, United States, 37232

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

United States, Washington

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States, 98109

France

Centre Hospitalier Régional Universitaire de Lille

Lille, France, 59037

Centre Hospitalier Lyon Sud

Pierre Benite, France, 69495

Sponsors and Collaborators

Kite, A Gilead Company

Investigators

• Study Director: Kite Study Director; Kite, A Gilead Company

More Information

Additional Information:

Gilead Clinical Trials Website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Kite, A Gilead Company
• ClinicalTrials.gov Identifier: NCT03105336
• Other Study ID Numbers: KTE-C19-105; 2017-001912-13 ( EudraCT Number ); 2023-505169-10 ( Other Identifier: European Medicines Agency )
• First Posted: April 7, 2017
• Last Update Posted: February 26, 2024
• Last Verified: February 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell, Marginal Zone; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Cyclophosphamide; Fludarabine; Axicabtagene ciloleucel; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological