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

Follicular Lymphoma Clinical Trial

— ZUMA-5  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03105336
• Other study ID #: KTE-C19-105
• Secondary ID: 2017-001912-1320
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 20, 2017
• Est. completion date: January 2025

Study information

• Verified date: February 2024
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 159
• Est. completion date: January 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Follicular Lymphoma
• Indolent Non-Hodgkin Lymphoma
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Non-Hodgkin
• Marginal Zone Lymphoma

Intervention

Biological:
• axicabtagene ciloleucel
A single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered intravenously.

Drug:
• Cyclophosphamide
Administered intravenously
• Fludarabine
Administered intravenously

Locations

Country	Name	City	State
France	Centre Hospitalier Régional Universitaire de Lille	Lille
France	Centre Hospitalier Lyon Sud	Pierre Benite
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Ohio State University Medical Center	Cleveland	Ohio
United States	Banner MD Anderson Cancer Center	Gilbert	Arizona
United States	Hackensack University Medical Center - John Theurer Cancer Center	Hackensack	New Jersey
United States	MD Anderson Cancer Center	Houston	Texas
United States	University of California Los Angeles	Los Angeles	California
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	University of Miami Hospital and Clinics	Miami	Florida
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center	New York	New York
United States	Fox Chase Cancer Center	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	University of Rochester Medical Center (URMC)	Rochester	New York
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	H Lee Moffitt Cancer Center	Tampa	Florida
United States	Georgetown Lombardi Comprehensive Cancer Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Kite, A Gilead Company

Countries where clinical trial is conducted

United States,  France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events		Up to 15 years
Secondary	Overall Survival (OS)	OS is defined as the time from KTE-C19 infusion to the date of death.	Up to 15 years
Secondary	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.
Secondary	Levels of cytokines in serum		At enrollment, prior to axicabtagene ciloleucel infusion on Day 0, Day 3, Day 7, Week 2, Week 4
Secondary	Percentage of Participants experiencing anti-axicabtagene ciloleucel antibodies		At enrollment, Week 4, Month 3, every 3 months up to Month 12
Secondary	Percentage of Participants Experiencing clinically significant changes in lab values		Up to 5 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

External Links

•   Gilead Clinical Trials Website