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

Primary Purpose

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

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
axicabtagene ciloleucel
Cyclophosphamide
Fludarabine
Sponsored by
Kite, A Gilead Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Follicular Lymphoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 6 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.

Sites / Locations

  • Banner MD Anderson Cancer Center
  • USC Norris Comprehensive Cancer Center
  • University of California Los Angeles
  • Georgetown Lombardi Comprehensive Cancer Center
  • University of Miami Hospital and Clinics
  • H Lee Moffitt Cancer Center
  • Dana Farber Cancer Institute
  • Hackensack University Medical Center - John Theurer Cancer Center
  • Columbia University Medical Center
  • University of Rochester Medical Center (URMC)
  • Ohio State University Medical Center
  • Fox Chase Cancer Center
  • UPMC Hillman Cancer Center
  • Sarah Cannon Research Institute
  • Vanderbilt University Medical Center
  • MD Anderson Cancer Center
  • Fred Hutchinson Cancer Research Center
  • Centre Hospitalier Régional Universitaire de Lille
  • Centre Hospitalier Lyon Sud

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

axicabtagene ciloleucel

Arm Description

Participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide, followed by a single infusion of CAR transduced autologous T cells.

Outcomes

Primary Outcome Measures

Objective response rate per central read
Complete response (CR) + partial response (PR) per the Lugano Classiciation (Cheson et al, 2014).

Secondary Outcome Measures

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)
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.
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.
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Overall Survival (OS)
OS is defined as the time from KTE-C19 infusion to the date of death.
Levels of anti-CD19 CAR T cells in blood
Levels of cytokines in serum
Percentage of Participants experiencing anti-axicabtagene ciloleucel antibodies
Percentage of Participants Experiencing clinically significant changes in lab values
Time to next Therapy
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
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
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
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
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

Full Information

First Posted
April 3, 2017
Last Updated
September 15, 2023
Sponsor
Kite, A Gilead Company
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1. Study Identification

Unique Protocol Identification Number
NCT03105336
Brief Title
A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma
Acronym
ZUMA-5
Official Title
A Phase 2 Multicenter Study of Axicabtagene Ciloleucel in Subjects With Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (iNHL)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 20, 2017 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Kite, A Gilead Company

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Follicular Lymphoma, Marginal Zone Lymphoma, Indolent Non-Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
159 (Actual)

8. Arms, Groups, and Interventions

Arm Title
axicabtagene ciloleucel
Arm Type
Experimental
Arm Description
Participants will receive a conditioning chemotherapy regimen of fludarabine and cyclophosphamide, followed by a single infusion of CAR transduced autologous T cells.
Intervention Type
Biological
Intervention Name(s)
axicabtagene ciloleucel
Other Intervention Name(s)
Axicab, Yescarta®
Intervention Description
A single infusion of axicabtagene ciloleucel CAR transduced autologous T cells administered intravenously.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Administered intravenously
Primary Outcome Measure Information:
Title
Objective response rate per central read
Description
Complete response (CR) + partial response (PR) per the Lugano Classiciation (Cheson et al, 2014).
Time Frame
Up to 15 years
Secondary Outcome Measure Information:
Title
CR Rate per central read
Description
CRR is defined as the incidence of CR as best response to treatment by the Lugano Classification (Cheson et al, 2014)
Time Frame
Up to 15 years
Title
DOR
Description
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.
Time Frame
Up to 15 years
Title
PFS
Description
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.
Time Frame
Up to 15 years
Title
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame
Up to 15 years
Title
Overall Survival (OS)
Description
OS is defined as the time from KTE-C19 infusion to the date of death.
Time Frame
Up to 15 years
Title
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.
Title
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
Title
Percentage of Participants experiencing anti-axicabtagene ciloleucel antibodies
Time Frame
At enrollment, Week 4, Month 3, every 3 months up to Month 12
Title
Percentage of Participants Experiencing clinically significant changes in lab values
Time Frame
Up to 5 years
Title
Time to next Therapy
Description
Time from axi-cel infusion date to the start of the subsequent new lymphoma therapy or death from any cause.
Time Frame
Up to 15 years
Title
Objective response rate among participants with 3 or more lines of prior therapy
Description
Complete response (CR) + partial response (PR) per the Lugano Classiciation (Cheson et al, 2014) for participants with 3 or more lines of prior therapy.
Time Frame
Up to 15 years
Title
Complete response rate among those participants with 3 or more lines of prior therapy
Description
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.
Time Frame
Up to 15 years
Title
Objective Response Rate as Determined by the Investigator Read
Description
ORR per investigator read is defined as the incidence of a CR or a PR by the Lugano Classification.
Time Frame
Up to 15 years
Title
Best Objective Response per Central Read or Investigator Read
Description
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
Time Frame
Up to 15 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: 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). Individual has [measurable disease]. Individual has no known presence or history of central nervous system (CNS) involvement by lymphoma. 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. Individual has Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and adequate renal, hepatic, pulmonary, and cardiac function 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: Transformed follicular lymphoma (FL) or marginal zone lymphoma (MZL) Small lymphocytic lymphoma Histological Grade 3b FL Individual will have undergone autologous transplant within 6 weeks of planned leukapheresis or has undergone allogeneic transplant. 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kite Study Director
Organizational Affiliation
Kite, A Gilead Company
Official's Role
Study Director
Facility Information:
Facility Name
Banner MD Anderson Cancer Center
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
USC Norris Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of California Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Georgetown Lombardi Comprehensive Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
University of Miami Hospital and Clinics
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
H Lee Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Hackensack University Medical Center - John Theurer Cancer Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Rochester Medical Center (URMC)
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Ohio State University Medical Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
UPMC Hillman Cancer Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Centre Hospitalier Régional Universitaire de Lille
City
Lille
ZIP/Postal Code
59037
Country
France
Facility Name
Centre Hospitalier Lyon Sud
City
Pierre Benite
ZIP/Postal Code
69495
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
35679476
Citation
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.
Results Reference
derived
PubMed Identifier
34895487
Citation
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.
Results Reference
derived
Links:
URL
https://www.gileadclinicaltrials.com/study/?id=KTE-C19-105
Description
Gilead Clinical Trials Website

Learn more about this trial

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

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