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Study of Axicabtagene Ciloleucel Given With Steroids In Participants With Relapsed Or Refractory Large B-Cell Lymphoma (ZUMA-24)

Primary Purpose

Relapsed or Refractory Large B-cell Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Axicabtagene Ciloleucel
Cyclophosphamide
Fludarabine
Dexamethasone
Sponsored by
Kite, A Gilead Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed or Refractory Large B-cell Lymphoma

Eligibility Criteria

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

Key Inclusion Criteria:

  • Histologically confirmed large B-cell lymphoma (LBCL), including the following types defined by World Health Organization (WHO) 2016 classification, by local pathology laboratory assessment, are eligible as defined below:

    • Diffuse large B-cell lymphoma (DLBCL) not otherwise specified.
    • High-grade B-cell lymphoma (HGBL) with or without MYC and BCL2 and/or BCL6 rearrangement.
    • DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV) + DLBCL.
    • Primary mediastinal (thymic) LBCL.
    • Primary cutaneous DLBCL, leg type.
    • Transformation of follicular lymphoma to DLBCL will also be included.
  • Relapsed or refractory disease after first-line chemotherapy.

  • Individuals must have received adequate prior therapy including:

    • Anti-CD20 monoclonal antibody AND
    • An anthracycline-containing chemotherapy regimen.
  • At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Individual agrees to outpatient treatment setting and to adhere to the prespecified clinical monitoring requirements.

Key Exclusion Criteria:

  • Received more than 1 line of therapy for LBCL.
  • History of autologous or allogeneic stem cell transplant.
  • Prior cluster of differentiation (CD)19 targeted therapy.
  • Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy.
  • Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor.
  • Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma. DLBCL epidural involvement should be considered as positive CNS disease.
  • In the investigator's judgment, the individual is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation.

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

Sites / Locations

  • City of Hope (City of Hope National Medical Center, City of Hope Medical Center)Recruiting
  • UCLARecruiting
  • Colorado Blood Cancer InstituteRecruiting
  • Advocate Aurora Health - Advocate Lutheran General Hospital
  • University of Maryland Greenebaum Comprehensive Cancer CenterRecruiting
  • Barbara Ann Karmanos Cancer InstituteRecruiting
  • John Theurer Cancer Center at Hackensack University Medical CenterRecruiting
  • Oncology Hematology Care Clinical Trials, LLCRecruiting
  • Prisma Health - UpstateRecruiting
  • Tennessee Oncology, PLLCRecruiting
  • Henry-Joyce Cancer ClinicRecruiting
  • Methodist Healthcare System of San AntonioRecruiting
  • Intermountain HealthcareRecruiting
  • Huntsman Cancer Institute, University of UtahRecruiting
  • University of Virginia Health SystemRecruiting
  • Virginia Oncology AssociatesRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Axicabtagene Ciloleucel

Arm Description

Participant will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m^2 and fludarabine 30 mg/m^2 ) over 3 days (Days -5, -4, and -3) followed by prophylactic corticosteroid treatment with 10 mg dexamethasone on Day 0 (prior to axicabtagene ciloleucel), Day 1, and Day 2. Participant will receive axicabtagene ciloleucel consisting of a single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells on Day 0 (following dexamethasone 10 mg) at a target dose of 2 x 10^6 cells/kg.

Outcomes

Primary Outcome Measures

Percentage and Severity of Participants with Treatment-emergent Cytokine Release Syndrome (CRS) and Neurologic Events

Secondary Outcome Measures

Time to Onset of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration
Duration of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration
Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 72 hours
Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 7 days
Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 14 days
Rates of Hospitalization After Axicabtagene ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 30 days
Duration of Initial Hospitalization After Axicabtagene Ciloleucel Infusion
Proportion of Intensive Care Unit (ICU) Admitted Participants
Duration of ICU Admission During First Hospitalization After Axicabtagene Ciloleucel Infusion
Percentage of Participants Experiencing Treatment- Emergent Adverse Events
Percentage of Participants Experiencing Treatment- Emergent Serious Adverse Events
Change in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) From Baseline to Month 6
The EQ-5D-5 levels (EQ-5D-5L) is a standardized measure of health status of the participant that provides a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of 2 components: a descriptive system of the participant's health and a rating of his or her current health state on a 0-100 VAS. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.
Objective Response Rate (ORR) as Assessed by Investigator Assessment
ORR is defined as the incidence of either a complete response or a partial response by the revised international working group (IWG) response criteria for malignant lymphoma.
Complete Response (CR) Rate as Assessed by Investigator Assessment
CR rate is defined as the incident of complete response.
Duration of response (DOR) as Assessed by Investigator Assessment
DOR is defined as the time from first objective response to disease progression per the revised IWG response criteria for malignant lymphoma or death from any cause.
Progression-free Survival (PFS) as Assessed by Investigator Assessment
PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per the revised IWG response criteria for malignant lymphoma or death from any cause.
Event Free Survival (EFS) as Assessed by Investigator Assessment
EFS is defined as the time from infusion to the earliest date of disease progression per the revised IWG response criteria for malignant lymphoma, commencement of new anti-lymphoma therapy, or death from any cause.
Overall Survival (OS)
OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
Peak Serum Levels of Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15
Peak Serum Levels of Inflammatory and Immune Modulating Cytokines: IFN-γ, IL-1, IL-6, IL- 13, IL-17, IL-1, IL-1RA, Granulocyte-macrophage Colony Stimulating Factor (GM-CSF), Tumor Necrosis Factor-Alpha (TNF-α), and IL-12p40/p70
IFN-γ=Interferon-Gamma, IL-1RA=IL-1 Receptor Antagonist
Peak Serum Levels of Immune Effector Molecules: Granzyme A, Granzyme B, and Perforin
Peak Serum Levels of the Acute Phase Response Proteins: C-Reactive Protein (CRP), Serum Amyloid A (SAA), Soluble IL-2 Receptor Alpha (sIL-1Ra), Ferritin
Peak Serum Levels of Chemokines: IL-8, C-X-C Motif Chemokine Ligand-10 (CXCL-10), and Monocyte Chemotactic Protein-1 (MCP-1).
Blood Levels of Axicabtagene Ciloleucel Chimeric Antigen Receptor (CAR) T-cells Over Time

Full Information

First Posted
July 13, 2022
Last Updated
October 23, 2023
Sponsor
Kite, A Gilead Company
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1. Study Identification

Unique Protocol Identification Number
NCT05459571
Brief Title
Study of Axicabtagene Ciloleucel Given With Steroids In Participants With Relapsed Or Refractory Large B-Cell Lymphoma
Acronym
ZUMA-24
Official Title
A Phase 2 Open-Label, Multicenter Study Evaluating The Safety And Efficacy of Axicabtagene Ciloleucel Concomitant With Prophylactic Steroids In Subjects With Relapsed Or Refractory Large B-Cell Lymphoma In The Outpatient Setting
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 9, 2022 (Actual)
Primary Completion Date
March 2026 (Anticipated)
Study Completion Date
March 2026 (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
No

5. Study Description

Brief Summary
The goal of this clinical study is to learn more about the study drug, axicabtagene ciloleucel, in participants with relapsed or refractory large B-cell lymphoma (LBCL) in the outpatient setting.
Detailed Description
Participants who complete at minimum 24 months follow up will be transitioned to a separate long-term follow-up study (study KT-US-982-5968) to 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
Relapsed or Refractory Large B-cell 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
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Axicabtagene Ciloleucel
Arm Type
Experimental
Arm Description
Participant will receive lymphodepleting chemotherapy (cyclophosphamide 500 mg/m^2 and fludarabine 30 mg/m^2 ) over 3 days (Days -5, -4, and -3) followed by prophylactic corticosteroid treatment with 10 mg dexamethasone on Day 0 (prior to axicabtagene ciloleucel), Day 1, and Day 2. Participant will receive axicabtagene ciloleucel consisting of a single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells on Day 0 (following dexamethasone 10 mg) at a target dose of 2 x 10^6 cells/kg.
Intervention Type
Biological
Intervention Name(s)
Axicabtagene Ciloleucel
Other Intervention Name(s)
Yescarta®
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Fludarabine
Intervention Description
Administered intravenously
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Administered orally or intravenously
Primary Outcome Measure Information:
Title
Percentage and Severity of Participants with Treatment-emergent Cytokine Release Syndrome (CRS) and Neurologic Events
Time Frame
Up to 24 months
Secondary Outcome Measure Information:
Title
Time to Onset of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration
Time Frame
First infusion date of axicabtagene ciloleucel up to 24 months
Title
Duration of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration
Time Frame
First infusion date of axicabtagene ciloleucel up to 24 months
Title
Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 72 hours
Time Frame
First infusion date of axicabtagene ciloleucel up to 72 hours
Title
Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 7 days
Time Frame
First infusion date of axicabtagene ciloleucel up to 7 days
Title
Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 14 days
Time Frame
First infusion date of axicabtagene ciloleucel up to 14 days
Title
Rates of Hospitalization After Axicabtagene ciloleucel Infusion as Measured by Proportion of Hospitalized Participants Within 30 days
Time Frame
First infusion date of axicabtagene ciloleucel up to 30 days
Title
Duration of Initial Hospitalization After Axicabtagene Ciloleucel Infusion
Time Frame
First infusion date of axicabtagene ciloleucel up to 24 months
Title
Proportion of Intensive Care Unit (ICU) Admitted Participants
Time Frame
Up to 24 months
Title
Duration of ICU Admission During First Hospitalization After Axicabtagene Ciloleucel Infusion
Time Frame
Up to 24 months
Title
Percentage of Participants Experiencing Treatment- Emergent Adverse Events
Time Frame
First infusion date of axicabtagene ciloleucel up to 24 months
Title
Percentage of Participants Experiencing Treatment- Emergent Serious Adverse Events
Time Frame
First infusion date of axicabtagene ciloleucel up to 24 months
Title
Change in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) From Baseline to Month 6
Description
The EQ-5D-5 levels (EQ-5D-5L) is a standardized measure of health status of the participant that provides a simple, generic measure of health for clinical and economic appraisal. EQ-5D-5L consists of 2 components: a descriptive system of the participant's health and a rating of his or her current health state on a 0-100 VAS. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.
Time Frame
Baseline, 6 Months
Title
Objective Response Rate (ORR) as Assessed by Investigator Assessment
Description
ORR is defined as the incidence of either a complete response or a partial response by the revised international working group (IWG) response criteria for malignant lymphoma.
Time Frame
Up to 24 months
Title
Complete Response (CR) Rate as Assessed by Investigator Assessment
Description
CR rate is defined as the incident of complete response.
Time Frame
Up to 24 months
Title
Duration of response (DOR) as Assessed by Investigator Assessment
Description
DOR is defined as the time from first objective response to disease progression per the revised IWG response criteria for malignant lymphoma or death from any cause.
Time Frame
Up to 24 months
Title
Progression-free Survival (PFS) as Assessed by Investigator Assessment
Description
PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per the revised IWG response criteria for malignant lymphoma or death from any cause.
Time Frame
Up to 24 months
Title
Event Free Survival (EFS) as Assessed by Investigator Assessment
Description
EFS is defined as the time from infusion to the earliest date of disease progression per the revised IWG response criteria for malignant lymphoma, commencement of new anti-lymphoma therapy, or death from any cause.
Time Frame
Up to 24 months
Title
Overall Survival (OS)
Description
OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
Time Frame
Up to 24 months
Title
Peak Serum Levels of Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15
Time Frame
Up to 24 months
Title
Peak Serum Levels of Inflammatory and Immune Modulating Cytokines: IFN-γ, IL-1, IL-6, IL- 13, IL-17, IL-1, IL-1RA, Granulocyte-macrophage Colony Stimulating Factor (GM-CSF), Tumor Necrosis Factor-Alpha (TNF-α), and IL-12p40/p70
Description
IFN-γ=Interferon-Gamma, IL-1RA=IL-1 Receptor Antagonist
Time Frame
Up to 24 months
Title
Peak Serum Levels of Immune Effector Molecules: Granzyme A, Granzyme B, and Perforin
Time Frame
Up to 24 months
Title
Peak Serum Levels of the Acute Phase Response Proteins: C-Reactive Protein (CRP), Serum Amyloid A (SAA), Soluble IL-2 Receptor Alpha (sIL-1Ra), Ferritin
Time Frame
Up to 24 months
Title
Peak Serum Levels of Chemokines: IL-8, C-X-C Motif Chemokine Ligand-10 (CXCL-10), and Monocyte Chemotactic Protein-1 (MCP-1).
Time Frame
Up to 24 months
Title
Blood Levels of Axicabtagene Ciloleucel Chimeric Antigen Receptor (CAR) T-cells Over Time
Time Frame
Up to 24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria: Histologically confirmed large B-cell lymphoma (LBCL), including the following types defined by World Health Organization (WHO) 2016 classification, by local pathology laboratory assessment, are eligible as defined below: Diffuse large B-cell lymphoma (DLBCL) not otherwise specified. High-grade B-cell lymphoma (HGBL) with or without MYC and BCL2 and/or BCL6 rearrangement. DLBCL associated with chronic inflammation; Epstein-Barr virus (EBV) + DLBCL. Primary mediastinal (thymic) LBCL. Primary cutaneous DLBCL, leg type. Transformation of follicular lymphoma to DLBCL will also be included. Relapsed or refractory disease after first-line chemotherapy. Individuals must have received adequate prior therapy including: Anti-CD20 monoclonal antibody AND An anthracycline-containing chemotherapy regimen. At least 1 measurable lesion according to the Lugano Response Criteria for Malignant Lymphoma. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Individual agrees to outpatient treatment setting and to adhere to the prespecified clinical monitoring requirements. Key Exclusion Criteria: Received more than 1 line of therapy for LBCL. History of autologous or allogeneic stem cell transplant. Prior cluster of differentiation (CD)19 targeted therapy. Prior chimeric antigen receptor therapy or other genetically modified T-cell therapy. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection and uncomplicated bacterial pharyngitis are permitted if responding to active treatment and after consultation with the Kite medical monitor. Individuals with detectable cerebrospinal fluid malignant cells, brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma. DLBCL epidural involvement should be considered as positive CNS disease. In the investigator's judgment, the individual is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation. Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Medical Information
Phone
844-454-5483(1-844-454-KITE)
Email
medinfo@kitepharma.com
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
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Individual Site Status
Recruiting
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Name
Advocate Aurora Health - Advocate Lutheran General Hospital
City
Park Ridge
State/Province
Illinois
ZIP/Postal Code
60068
Country
United States
Individual Site Status
Withdrawn
Facility Name
University of Maryland Greenebaum Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Name
Barbara Ann Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Name
John Theurer Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Recruiting
Facility Name
Oncology Hematology Care Clinical Trials, LLC
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Individual Site Status
Recruiting
Facility Name
Prisma Health - Upstate
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29615
Country
United States
Individual Site Status
Recruiting
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
Henry-Joyce Cancer Clinic
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Name
Methodist Healthcare System of San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
Intermountain Healthcare
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Individual Site Status
Recruiting
Facility Name
Huntsman Cancer Institute, University of Utah
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84112
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Virginia Health System
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22908
Country
United States
Individual Site Status
Recruiting
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.gileadclinicaltrials.com/study/?id=KT-US-482-0137
Description
Gilead Clinical Trials Website

Learn more about this trial

Study of Axicabtagene Ciloleucel Given With Steroids In Participants With Relapsed Or Refractory Large B-Cell Lymphoma

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