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A Phase II Study of Axicabtagene Ciloleucel, an Anti-CD19 Chimeric Antigen Receptor (CAR) Tcell Therapy, in Combination With Radiotherapy (RT) in Relapsed/Refractory Follicular Lymphoma

Primary Purpose

Follicular Lymphoma

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Axicabtagene Ciloleucel
Cyclophosphamide
Fludarabine phosphate
Prednisone
Diphenhydramine
Acetaminophen
Sponsored by
M.D. Anderson Cancer Center
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

Inclusion Criteria: Eligible subjects will be considered for inclusion if they meet all of the following criteria: Men and women 18 years of age or older Histologically proven FL (Grade 1-3A) Relapsed or refractory following 2 or more prior lines of systemic therapy Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Medically appropriate for CAR-T cell therapy: adequate organ function CrCL >/= 45 mL/min/m2, hemoglobin level ≥ 8 g/dl, serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 x ULN if documented liver involvement, baseline oxygen saturation levels (SpO2) ≥92% on room air Have at least 2 measurable lesions on imaging, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) and ≥1 cm on CT, MRI, or clinical exam. At least one lesion will be omitted from the radiation treatment field. Prior radiation therapy is permitted provided normal tissue tolerance is not exceeded Female of child-bearing potential (FOCBP, defined below) must have a negative pregnancy test within 1 week of simulation for RT Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Histologic evidence of transformed follicular lymphoma, or follicular lymphoma grade 3B History of invasive malignancy requiring active therapy (systemic therapy, radiation, or surgery) within the past 3 years, excluding non-melanomatous skin cancer Women of childbearing potential who are pregnant Women who are breastfeeding and unwilling to discontinue prior to lymphodepleting chemotherapy and for 12 months following lymphodepleting chemotherapy and CAR-T cell infusion Urgent need for bridging chemotherapy or rituximab between apheresis and CAR T cell product infusion (steroids permitted) Additional RT would exceed standard organ at risk constraints History of severe, immediate hypersensitivity reaction attributed to aminoglycosides Uncontrolled fungal, bacterial, or viral infection requiring intravenous antimicrobials for management. Urinary tract infection and uncomplicated bacterial pharyngitis is permitted if responding to active treatment. Recent COVID19 infection is permitted if patient is deemed medically stable for CAR-T cell therapy.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Axicabtagene Ciloleuce

    Arm Description

    Participants will first have a procedure to collect your white blood cells that will be used to make axicabtagene ciloleucel. Then participatns will receive radiation therapy, followed by conditioning chemotherapy and 1 infusion of axicabtagene ciloleucel.

    Outcomes

    Primary Outcome Measures

    Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

    Secondary Outcome Measures

    Full Information

    First Posted
    September 12, 2023
    Last Updated
    September 21, 2023
    Sponsor
    M.D. Anderson Cancer Center
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06043323
    Brief Title
    A Phase II Study of Axicabtagene Ciloleucel, an Anti-CD19 Chimeric Antigen Receptor (CAR) Tcell Therapy, in Combination With Radiotherapy (RT) in Relapsed/Refractory Follicular Lymphoma
    Official Title
    A Phase II Study of Axicabtagene Ciloleucel, an Anti-CD19 Chimeric Antigen Receptor (CAR) Tcell Therapy, in Combination With Radiotherapy (RT) in Relapsed/Refractory Follicular Lymphoma
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 31, 2024 (Anticipated)
    Primary Completion Date
    September 1, 2026 (Anticipated)
    Study Completion Date
    September 1, 2028 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    M.D. Anderson Cancer Center

    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
    To learn about the safety of a drug called axicabtagene ciloleucel given in combination with radiation therapy to patients with relapsed/refractory FL.
    Detailed Description
    Primary Objectives: -The primary objective of this study is to determine the safety of standard of care axicabtagene ciloleucel with bridging radiotherapy (RT) in patients with relapsed/refractory follicular lymphoma, as assessed by the incidence of grade 3 or higher cytokine release syndrome (CRS) within 30 days after chimeric antigen receptor (CAR) T-cell infusion. Secondary Objectives: Establish the rates of CRS and ICANS in patients treated with CAR T-cell therapy and radiation Determine complete response rate (CR) at approximately 1 month post CAR T-cell ---therapy Determine the overall response rate (ORR) Determine the duration of response (DOR) Determine progression free survival (PFS) Determine overall survival (OS) Exploratory Objectives: -Assess the impact of tumor burden as measured by metabolic tumor volume and total lesion glycolysis on PET/CT on response following CAR T-cell infusion

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Follicular 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
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Axicabtagene Ciloleuce
    Arm Type
    Experimental
    Arm Description
    Participants will first have a procedure to collect your white blood cells that will be used to make axicabtagene ciloleucel. Then participatns will receive radiation therapy, followed by conditioning chemotherapy and 1 infusion of axicabtagene ciloleucel.
    Intervention Type
    Drug
    Intervention Name(s)
    Axicabtagene Ciloleucel
    Intervention Description
    Given by IV (vein)
    Intervention Type
    Drug
    Intervention Name(s)
    Cyclophosphamide
    Other Intervention Name(s)
    Cytoxan®, Neosar®
    Intervention Description
    Given by IV (vein)
    Intervention Type
    Drug
    Intervention Name(s)
    Fludarabine phosphate
    Intervention Description
    Given by IV (vein)
    Intervention Type
    Drug
    Intervention Name(s)
    Prednisone
    Intervention Description
    Given by IV (vein)
    Intervention Type
    Drug
    Intervention Name(s)
    Diphenhydramine
    Other Intervention Name(s)
    Benadryl®
    Intervention Description
    Given by IV (vein)
    Intervention Type
    Drug
    Intervention Name(s)
    Acetaminophen
    Other Intervention Name(s)
    Tylenol®, Dorcol®, Feverall, Panadol, APAP, N-Acetyl-P-Aminophenol, Paracetamo, Ofirmev™
    Intervention Description
    Given by IV (vein)
    Primary Outcome Measure Information:
    Title
    Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
    Time Frame
    through study completion; an average of 1 year

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Eligible subjects will be considered for inclusion if they meet all of the following criteria: Men and women 18 years of age or older Histologically proven FL (Grade 1-3A) Relapsed or refractory following 2 or more prior lines of systemic therapy Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 Medically appropriate for CAR-T cell therapy: adequate organ function CrCL >/= 45 mL/min/m2, hemoglobin level ≥ 8 g/dl, serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels ≤ 2.5 × upper limit of normal (ULN) or ≤ 5 x ULN if documented liver involvement, baseline oxygen saturation levels (SpO2) ≥92% on room air Have at least 2 measurable lesions on imaging, defined as lesions that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) and ≥1 cm on CT, MRI, or clinical exam. At least one lesion will be omitted from the radiation treatment field. Prior radiation therapy is permitted provided normal tissue tolerance is not exceeded Female of child-bearing potential (FOCBP, defined below) must have a negative pregnancy test within 1 week of simulation for RT Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Histologic evidence of transformed follicular lymphoma, or follicular lymphoma grade 3B History of invasive malignancy requiring active therapy (systemic therapy, radiation, or surgery) within the past 3 years, excluding non-melanomatous skin cancer Women of childbearing potential who are pregnant Women who are breastfeeding and unwilling to discontinue prior to lymphodepleting chemotherapy and for 12 months following lymphodepleting chemotherapy and CAR-T cell infusion Urgent need for bridging chemotherapy or rituximab between apheresis and CAR T cell product infusion (steroids permitted) Additional RT would exceed standard organ at risk constraints History of severe, immediate hypersensitivity reaction attributed to aminoglycosides Uncontrolled fungal, bacterial, or viral infection requiring intravenous antimicrobials for management. Urinary tract infection and uncomplicated bacterial pharyngitis is permitted if responding to active treatment. Recent COVID19 infection is permitted if patient is deemed medically stable for CAR-T cell therapy.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Susan Wu, MD
    Phone
    (281) 630-7607
    Email
    sywu1@mdanderson.org
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Susan Wu, MD
    Organizational Affiliation
    M.D. Anderson Cancer Center
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Links:
    URL
    http://www.mdanderson.org
    Description
    M D Anderson Cancer Center

    Learn more about this trial

    A Phase II Study of Axicabtagene Ciloleucel, an Anti-CD19 Chimeric Antigen Receptor (CAR) Tcell Therapy, in Combination With Radiotherapy (RT) in Relapsed/Refractory Follicular Lymphoma

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