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

Kite, A Gilead Company35 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Relapsed or Refractory Large B-cell Lymphoma

Interventions

Axicabtagene CiloleucelBIOLOGICAL

Administered intravenously

CyclophosphamideDRUG

Administered intravenously

FludarabineDRUG

Administered intravenously

Dexamethasone

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 1 or more lines of therapy. * 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: * 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.

Locations (16)

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

Duarte, California, United States

UCLA

Los Angeles, California, United States

Outcomes

Primary Outcomes

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

Time frame: Up to 24 months

Secondary Outcomes

Time to Onset of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration

Time frame: First infusion date of axicabtagene ciloleucel up to 24 months

Duration of CRS and Neurologic Events Following Axicabtagene Ciloleucel Administration

Time frame: First infusion date of axicabtagene ciloleucel up to 24 months

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

Rates of Hospitalization After Axicabtagene Ciloleucel Infusion as Measured by Proportion of Hospitalized Participants 3 Days After Infusion Date

Time frame: First infusion date of axicabtagene ciloleucel up to 3 days

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

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

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

Data from ClinicalTrials.gov

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Administered orally or intravenously

Colorado Blood Cancer Institute

Denver, Colorado, United States

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, United States

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Oncology Hematology Care Clinical Trials, LLC

Cincinnati, Ohio, United States

Prisma Health - Upstate

Greenville, South Carolina, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Henry-Joyce Cancer Clinic

Nashville, Tennessee, United States

...and 6 more locations

Duration of Initial Hospitalization After Axicabtagene Ciloleucel Infusion

Time frame: First infusion date of axicabtagene ciloleucel up to 24 months

Proportion of Intensive Care Unit (ICU) Admitted Participants

Time frame: Up to 24 months

Duration of ICU Admission During First Hospitalization After Axicabtagene Ciloleucel Infusion

Time frame: Up to 24 months

Percentage of Participants Experiencing Treatment- Emergent Adverse Events

Time frame: First infusion date of axicabtagene ciloleucel up to 24 months

Percentage of Participants Experiencing Treatment- Emergent Serious Adverse Events

Time frame: First infusion date of axicabtagene ciloleucel up to 24 months

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.

Time frame: Baseline, 6 Months

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.

Time frame: Up to 24 months

Complete Response (CR) Rate as Assessed by Investigator Assessment

CR rate is defined as the incident of complete response.

Time frame: Up to 24 months

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.

Time frame: Up to 24 months

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.

Time frame: Up to 24 months

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.

Time frame: Up to 24 months

Overall Survival (OS)

OS is defined as the time from axicabtagene ciloleucel infusion to the date of death.

Time frame: Up to 24 months

Peak Serum Levels of Homeostatic/Proliferative Cytokines: Interleukin (IL)-2, IL-7, and IL-15

Time frame: Up to 24 months

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

Time frame: Up to 24 months

Peak Serum Levels of Immune Effector Molecules: Granzyme A, Granzyme B, and Perforin

Time frame: Up to 24 months

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

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

Blood Levels of Axicabtagene Ciloleucel Chimeric Antigen Receptor (CAR) T-cells Over Time

Time frame: Up to 24 months