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Study of KITE-197 in Participants With Relapsed or Refractory Large B-cell Lymphoma

Primary Purpose

Relapsed/Refractory Large B-cell Lymphoma

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
KITE-197
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 Relapsed/Refractory Large B-cell Lymphoma

Eligibility Criteria

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

Key Inclusion Criteria: Relapsed or Refractory Large B-cell Lymphoma At least 1 measurable lesion Adequate organ and bone marrow function Key Exclusion Criteria: History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease free for at least 2 years History of Richter's transformation of chronic leukemic lymphoma History of allogenic stem cell transplant (SCT) Autologous SCT within 6 weeks of planned KITE-197 infusion Prior CD19 targeted antibody, such as tafasitamab and loncastuximab with the exception of individuals who have previously achieved an objective response to such therapy and their tumor expresses CD19 by International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (IHC) at the time of screening. Individuals who meet these criteria may be eligible Prior treatment with bendamustine within 6 months of enrollment Prior CAR therapy or other genetically modified cell therapy Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management History of HIV infection or acute or chronic active hepatitis B or C infection History or presence of a clinically significant central nervous system (CNS) disorder Note: Prior or active CNS involvement by lymphoma is not an exclusion criterion. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac disease within 12 months before enrollment Presence of primary immunodeficiency History of autoimmune disease (eg, Crohn's disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years History of symptomatic deep vein thrombosis (DVT) or pulmonary embolism within 3 months before enrollment. Catheter induced DVT which has been treated for at least 6 weeks prior to enrollment is permitted Females of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    KITE-197

    Arm Description

    Phase 1a (Dose Escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-197 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-197. Phase 1b (Dose Expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-197 CAR-transduced autologous T cells at 1 or more dose-level deemed to be tolerable.

    Outcomes

    Primary Outcome Measures

    Phase 1a: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs)
    Phase 1b: Complete Remission (CR) Rate
    Complete remission rate is defined as the proportion of participants with complete remission, per international working group (IWG) Lugano classification, as assessed by the investigator.

    Secondary Outcome Measures

    Percentage of Participants Experiencing Adverse Events (AEs)
    Percentage of Participants Experiencing Serious Adverse Events (SAEs)
    Overall Response Rate (ORR)
    ORR is defined as the proportion of participants with best objective response of either a CR or a partial response (PR) during the trial prior to any new anti-lymphoma therapy, per the Lugano Classification, as determined by the investigator.
    Duration of Response (DOR)
    DOR is defined as the time from first objective response to disease progression or death from any cause among participants who have achieved CR or PR per the Lugano Classification, as determined by the investigator.
    Progression-Free Survival (PFS)
    PFS is defined as the time from KITE-197 infusion to disease progression per the Lugano Classification, as determined by investigator review or death from any cause.
    Event Free Survival (EFS)
    EFS is defined as the time from KITE-197 infusion to the earliest occurrence of death due to any cause, disease progression/relapse per investigator, or initiation of new anti-lymphoma therapy.
    Time to Next Treatment (TTNT)
    TTNT is defined as time from KITE-197 infusion to the start of subsequent new lymphoma therapy or death from any cause.
    Overall Survival (OS)
    OS is defined as the time from KITE-197 infusion to death from any cause.
    Number of KITE-197 CAR T Cells in Blood Over Time Post Infusion
    Proportion of Immune Cell Subsets in KITE-197

    Full Information

    First Posted
    October 6, 2023
    Last Updated
    October 23, 2023
    Sponsor
    Kite, A Gilead Company
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06079164
    Brief Title
    Study of KITE-197 in Participants With Relapsed or Refractory Large B-cell Lymphoma
    Official Title
    A Phase 1 Open-label, Single Arm, Multicenter Study Evaluating the Safety and Efficacy of KITE-197 in Subjects With Relapsed or Refractory Large B-cell Lymphoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 2023 (Anticipated)
    Primary Completion Date
    March 2025 (Anticipated)
    Study Completion Date
    December 2027 (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
    This study will have two Phases: Phase 1a and Phase 1b. The goal of Phase 1a of this clinical study is to learn more about the safety, tolerability and dosing of study drug KITE-197, in participants with relapsed or refractory large B-cell lymphoma (r/rLBCL). The goal of Phase 1b of this clinical study is learn about the effectiveness of the recommended dose of KITE-197 in participants with r/r LBCL. The primary objectives of this study are: Phase 1a: To evaluate the safety of KITE-197 in participants with r/r LBCL and determine the target dose level for Phase 1b. Phase 1b: To evaluate the efficacy of KITE-197 in participants with r/r LBCL as measured by the complete remission (CR) rate.
    Detailed Description
    Participants will be followed for approximately 24 months after the infusion of KITE-197 before transitioning to a separate Kite long-term follow-up study KT-US-982-5968, in which they will be followed for the remainder of the 15-year follow-up period.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Relapsed/Refractory Large B-cell Lymphoma

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    39 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    KITE-197
    Arm Type
    Experimental
    Arm Description
    Phase 1a (Dose Escalation): Participants with r/r large B-cell lymphoma will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single target starting dose of KITE-197 chimeric antigen receptor (CAR) transduced autologous T cells. Based on dose limiting toxicities (DLTs) observed in the first cohort, additional participants will be enrolled and administered escalating dose of KITE-197. Phase 1b (Dose Expansion): After completion of dose escalation, additional participants with r/r B-cell lymphoma across different disease indications will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single dose of KITE-197 CAR-transduced autologous T cells at 1 or more dose-level deemed to be tolerable.
    Intervention Type
    Drug
    Intervention Name(s)
    KITE-197
    Intervention Description
    A single infusion of CAR-transduced autologous T cells administered intravenously
    Intervention Type
    Drug
    Intervention Name(s)
    Cyclophosphamide
    Intervention Description
    Lymphodepleting chemotherapy administered intravenously
    Intervention Type
    Drug
    Intervention Name(s)
    Fludarabine
    Intervention Description
    Lymphodepleting chemotherapy administered intravenously
    Primary Outcome Measure Information:
    Title
    Phase 1a: Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs)
    Time Frame
    First infusion date of KITE-197 up to 28 days
    Title
    Phase 1b: Complete Remission (CR) Rate
    Description
    Complete remission rate is defined as the proportion of participants with complete remission, per international working group (IWG) Lugano classification, as assessed by the investigator.
    Time Frame
    Up to 24 months
    Secondary Outcome Measure Information:
    Title
    Percentage of Participants Experiencing Adverse Events (AEs)
    Time Frame
    Enrollment up to 24 months plus 30 days
    Title
    Percentage of Participants Experiencing Serious Adverse Events (SAEs)
    Time Frame
    Enrollment up to 24 months plus 30 days
    Title
    Overall Response Rate (ORR)
    Description
    ORR is defined as the proportion of participants with best objective response of either a CR or a partial response (PR) during the trial prior to any new anti-lymphoma therapy, per the Lugano Classification, as determined by the investigator.
    Time Frame
    Up to 24 months
    Title
    Duration of Response (DOR)
    Description
    DOR is defined as the time from first objective response to disease progression or death from any cause among participants who have achieved CR or PR per the Lugano Classification, as determined by the investigator.
    Time Frame
    Up to 24 months
    Title
    Progression-Free Survival (PFS)
    Description
    PFS is defined as the time from KITE-197 infusion to disease progression per the Lugano Classification, as determined by investigator review or death from any cause.
    Time Frame
    Up to 24 months
    Title
    Event Free Survival (EFS)
    Description
    EFS is defined as the time from KITE-197 infusion to the earliest occurrence of death due to any cause, disease progression/relapse per investigator, or initiation of new anti-lymphoma therapy.
    Time Frame
    Up to 24 months
    Title
    Time to Next Treatment (TTNT)
    Description
    TTNT is defined as time from KITE-197 infusion to the start of subsequent new 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 KITE-197 infusion to death from any cause.
    Time Frame
    Up to 24 months
    Title
    Number of KITE-197 CAR T Cells in Blood Over Time Post Infusion
    Time Frame
    Up to 24 months
    Title
    Proportion of Immune Cell Subsets in KITE-197
    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: Relapsed or Refractory Large B-cell Lymphoma At least 1 measurable lesion Adequate organ and bone marrow function Key Exclusion Criteria: History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (eg, cervix, bladder, breast) unless disease free for at least 2 years History of Richter's transformation of chronic leukemic lymphoma History of allogenic stem cell transplant (SCT) Autologous SCT within 6 weeks of planned KITE-197 infusion Prior CD19 targeted antibody, such as tafasitamab and loncastuximab with the exception of individuals who have previously achieved an objective response to such therapy and their tumor expresses CD19 by International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (IHC) at the time of screening. Individuals who meet these criteria may be eligible Prior treatment with bendamustine within 6 months of enrollment Prior CAR therapy or other genetically modified cell therapy Presence or suspicion of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management History of HIV infection or acute or chronic active hepatitis B or C infection History or presence of a clinically significant central nervous system (CNS) disorder Note: Prior or active CNS involvement by lymphoma is not an exclusion criterion. History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, New York Heart Association Class II or greater congestive heart failure, or other clinically significant cardiac disease within 12 months before enrollment Presence of primary immunodeficiency History of autoimmune disease (eg, Crohn's disease, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years History of symptomatic deep vein thrombosis (DVT) or pulmonary embolism within 3 months before enrollment. Catheter induced DVT which has been treated for at least 6 weeks prior to enrollment is permitted Females of childbearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant 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

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Links:
    URL
    https://www.gileadclinicaltrials.com/study?nctid=NCT06079164
    Description
    Gilead Clinical Trials Website

    Learn more about this trial

    Study of KITE-197 in Participants With Relapsed or Refractory Large B-cell Lymphoma

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