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

• ClinicalTrials.gov Identifier: NCT05459571
• Recruitment Status: Recruiting
• First Posted: July 15, 2022
• Last Update Posted: May 9, 2023
• Sponsor: Kite, A Gilead Company
• Information provided by (Responsible Party): Gilead Sciences ( Kite, A Gilead Company )

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.

Condition or disease	Intervention/treatment	Phase
Relapsed or Refractory Large B-cell Lymphoma	Biological: Axicabtagene Ciloleucel; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Dexamethasone	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: August 10, 2022
• Estimated Primary Completion Date: March 2026
• Estimated Study Completion Date: March 2026

Arms and Interventions

Arm

Intervention/treatment

Experimental: Axicabtagene Ciloleucel; 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.

Biological: Axicabtagene Ciloleucel; Administered intravenously; Other Name: Yescarta®; Drug: Cyclophosphamide; Administered intravenously; Drug: Fludarabine; Administered intravenously; Drug: Dexamethasone; Administered orally or intravenously

Outcome Measures

Primary Outcome Measures :

1. Percentage and Severity of Participants with Treatment-emergent Cytokine Release Syndrome (CRS) and Neurologic Events [ Time Frame: Up to 24 months ]

Secondary Outcome Measures :

1. Time to Onset of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration [ Time Frame: First infusion date of axicabtagene ciloleucel up to 24 months ]
2. Duration of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration [ Time Frame: First infusion date of axicabtagene ciloleucel up to 24 months ]
3. 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 ]
4. 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 ]
5. 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 ]
6. 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 ]
7. Duration of Initial Hospitalization After Axicabtagene Ciloleucel Infusion [ Time Frame: First infusion date of axicabtagene ciloleucel up to 24 months ]
8. Proportion of Intensive Care Unit (ICU) Admitted Participants [ Time Frame: Up to 24 months ]
9. Duration of ICU Admission During First Hospitalization After Axicabtagene Ciloleucel Infusion [ Time Frame: Up to 24 months ]
10. Percentage of Participants Experiencing Treatment- Emergent Adverse Events [ Time Frame: First infusion date of axicabtagene ciloleucel up to 24 months ]
11. Percentage of Participants Experiencing Treatment- Emergent Serious Adverse Events [ Time Frame: First infusion date of axicabtagene ciloleucel up to 24 months ]
12. Change in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) From Baseline to Month 6 [ Time Frame: Baseline, 6 Months ]
    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.
13. Objective Response Rate (ORR) as Assessed by Investigator Assessment [ Time Frame: Up to 24 months ]
    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.
14. Complete Response (CR) Rate as Assessed by Investigator Assessment [ Time Frame: Up to 24 months ]
    CR rate is defined as the incident of complete response.
15. Duration of response (DOR) as Assessed by Investigator Assessment [ Time Frame: Up to 24 months ]
    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.
16. Progression-free Survival (PFS) as Assessed by Investigator Assessment [ Time Frame: Up to 24 months ]
    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.
17. Event Free Survival (EFS) as Assessed by Investigator Assessment [ Time Frame: Up to 24 months ]
    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.
18. Overall Survival (OS) [ Time Frame: Up to 24 months ]
    OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.
19. Peak Serum Levels of Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15 [ Time Frame: Up to 24 months ]
20. 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 [ Time Frame: Up to 24 months ]
    IFN-γ=Interferon-Gamma, IL-1RA=IL-1 Receptor Antagonist
21. Peak Serum Levels of Immune Effector Molecules: Granzyme A, Granzyme B, and Perforin [ Time Frame: Up to 24 months ]
22. 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 ]
23. 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 ]
24. Blood Levels of Axicabtagene Ciloleucel Chimeric Antigen Receptor (CAR) T-cells Over Time [ Time Frame: Up to 24 months ]

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:

• 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.

Contacts and Locations

Contacts

Contact: Medical Information; 844-454-5483(1-844-454-KITE); medinfo@kitepharma.com

Locations

United States, California

City of Hope (City of Hope National Medical Center, City of Hope Medical Center); Recruiting

Duarte, California, United States, 91010

UCLA; Recruiting

Los Angeles, California, United States, 90025

United States, Colorado

Colorado Blood Cancer Institute; Recruiting

Denver, Colorado, United States, 80218

United States, Illinois

Advocate Aurora Health - Advocate Lutheran General Hospital; Recruiting

Park Ridge, Illinois, United States, 60068

United States, Michigan

Barbara Ann Karmanos Cancer Institute; Recruiting

Detroit, Michigan, United States, 48201

United States, New Jersey

John Theurer Cancer Center at Hackensack University Medical Center; Recruiting

Hackensack, New Jersey, United States, 07601

United States, Tennessee

Tennessee Oncology, PLLC; Recruiting

Nashville, Tennessee, United States, 37203

Henry-Joyce Cancer Clinic; Recruiting

Nashville, Tennessee, United States, 37232

United States, Texas

Methodist Healthcare System of San Antonio; Recruiting

San Antonio, Texas, United States, 78229

United States, Utah

Intermountain Healthcare; Recruiting

Murray, Utah, United States, 84107

Huntsman Cancer Institute, University of Utah; Recruiting

Salt Lake City, Utah, United States, 84112

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 

• Responsible Party: Kite, A Gilead Company
• ClinicalTrials.gov Identifier: NCT05459571
• Other Study ID Numbers: KT-US-482-0137
• First Posted: July 15, 2022
• Last Update Posted: May 9, 2023
• Last Verified: May 2023

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, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Dexamethasone; 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; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists