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 )

Tracking Information

• First Submitted Date: April 3, 2017
• First Posted Date: April 7, 2017
• Last Update Posted Date: February 26, 2024
• Actual Study Start Date: June 20, 2017
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 19, 2018)

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).

Original Primary Outcome Measures (submitted: April 3, 2017)

Objective response rate [ Time Frame: 6 months ]

Complete response (CR) + partial response (PR) per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma (Cheson 2007) as determined by the study investigators.

Current Secondary Outcome Measures (submitted: April 18, 2023)

• 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)
• 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.
• 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.
• Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 15 years ]
• Overall Survival (OS) [ Time Frame: Up to 15 years ]
  OS is defined as the time from KTE-C19 infusion to the date of death.
• 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. ]
• 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 ]
• Percentage of Participants experiencing anti-axicabtagene ciloleucel antibodies [ Time Frame: At enrollment, Week 4, Month 3, every 3 months up to Month 12 ]
• Percentage of Participants Experiencing clinically significant changes in lab values [ Time Frame: Up to 5 years ]
• 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.
• 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.
• 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.
• 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.
• 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

Original Secondary Outcome Measures (submitted: April 3, 2017)

• Progression Free Survival [ Time Frame: 12 months ]
  The time from the axicabtagene ciloleucel infusion date to the date of disease progression per the revised IWG Response Criteria for Malignant Lymphoma (Cheson 2007) or death from any cause.
• Overall Survival [ Time Frame: 12 months ]
  Defined as the time from axicabtagene ciloleucel infusion to the date of death.
• Incidences of AEs [ Time Frame: 12 months ]
  The frequency of any AEs that occurred during study participation.
• Clinical significant changes in lab values. [ Time Frame: 12 months ]
  The occurrence of any changes in lab values deemed to be clinically significant during study participation.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
• Official Title: A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL)
• 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.
• 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
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Follicular Lymphoma
• Marginal Zone Lymphoma
• Indolent Non-Hodgkin Lymphoma

Intervention

• 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

Study Arms

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.

Interventions:

• Biological: axicabtagene ciloleucel
• Drug: Cyclophosphamide
• Drug: Fludarabine

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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 24, 2022): 159
• Original Estimated Enrollment (submitted: April 3, 2017): 50
• Estimated Study Completion Date: January 2025
• Estimated Primary Completion Date: January 2025 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, United States

Administrative Information

• NCT Number: NCT03105336
• Other Study ID Numbers: KTE-C19-105; 2017-001912-13 ( EudraCT Number ); 2023-505169-10 ( Other Identifier: European Medicines Agency )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Gilead Sciences ( Kite, A Gilead Company )
• Original Responsible Party: Same as current
• Current Study Sponsor: Kite, A Gilead Company
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Gilead Sciences
• Verification Date: February 2024