Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma

Kite, A Gilead Company27 enrolled

Overview

The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.

Following at least 24 months of assessments after axicabtagene ciloleucel infusion, participants will be asked to rollover to a separate long-term follow-up study (Study KT-US-982-5968). Participants will complete the remainder of the 15-year follow-up assessments in the KT-US-982-5968 study.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Refractory Large B-cell Lymphoma

Interventions

Axicabtagene CiloleucelBIOLOGICAL

A single infusion of CAR-transduced autologous T cells administered intravenously

RituximabDRUG

Administered intravenously

FludarabineDRUG

Administered according to package insert

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * Histologically confirmed large B-cell lymphoma * Chemotherapy-refractory disease, defined as one or more of the following: * No response to first-line therapy (primary refractory disease) * No response to second or greater lines of therapy OR * Refractory after autologous stem cell transplant (ASCT) * At least 1 measureable lesion according to the Lugano Classification (Cheson 2014). * Individuals must have received adequate prior therapy, including at a minimum: * Anti-CD20 monoclonal antibody * An anthracycline-containing chemotherapy regimen * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Adequate renal, hepatic, pulmonary, and cardiac function Key Exclusion Criteria: * Known CD19 negative or CD20 negative tumor * History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL) * Prior CAR therapy or other genetically modified T-cell therapy * Prior organ transplantation including prior allogeneic stem cell transplant (SCT) * Prior CD19 targeted therapy * Clinically significant infection or cardiopulmonary disease * Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed) * History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases * History of autoimmune disease * History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (14)

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

City of Hope National Medical Center

Duarte, California, United States

Outcomes

Primary Outcomes

Complete Response (CR) Rate Per the International Working Group (IWG) Lugano Classification as Determined by Study Investigators

CR rate is defined as the incidence of a CR per the IWG Lugano Classification as determined by study investigators. CR rate: percentage of participants with CR \[complete metabolic response (CMR); complete radiological response (CRR)\]. CMR: positron emission tomography (PET) 5-point scale (5-PS) scores of 1 (no uptake above background), 2 (uptake ≤ mediastinum), 3 (uptake \> mediastinum but ≤ liver) with/without a residual mass); no new lesions; and no evidence of fluorodeoxyglucose (FDG)-avid disease in bone marrow (BM). CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in longest transverse diameter of lesion (LDi); no extralymphatic sites of disease; absent non-measured lesion (NMLs); organ enlargement regress to normal; no new sites; and bone marrow normal by morphology. 95% confidence interval (CI) was calculated by Clopper-Pearson method.

Time frame: First infusion date up to maximum duration of 32.7 months

Secondary Outcomes

Percentage of Participants Who Experienced Treatment Emergent Adverse Events (TEAEs)

An AE is defined as any untoward medical occurrence in a clinical trial participant that does not necessarily have a relationship with study treatment or worsening of a pre-existing medical condition. TEAEs are any AEs with onset on or after axicabtagene ciloleucel infusion or worsening of a pre-existing medical condition that occurs on or after axicabtagene ciloleucel infusion.

Time frame: First infusion date up to maximum duration of 27 months

Percentage of Participants Who Experienced Laboratory Toxicity Grade Shifts to Grade 3 or Higher Resulting From Increased Parameter Value

Grading categories were determined by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Laboratory parameters with only non-zero values are presented.

Time frame: First infusion date up to maximum duration of 27 months

Objective Response Rate (ORR) Per the IWG Lugano Classification as Determined by Study Investigators

Data from ClinicalTrials.gov

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Administered according to package insert

Stanford Cancer Institute

Palo Alto, California, United States

UCLA Hematology/Oncology

Santa Monica, California, United States

Mayo Clinic Florida

Jacksonville, Florida, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Mayo Clinic

Rochester, Minnesota, United States

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, United States

Columbia University Medical Center, New York Presbyterian Hospital

New York, New York, United States

...and 4 more locations

ORR: percentage of participants with CR \[CMR;CRR\] or PR \[partial metabolic response (PMR); partial radiologic response (PRR)\].CMR: PET 5PS scores of 1 (no uptake above background, 2 (uptake ≤ mediastinum), 3 (uptake \> mediastinum but ≤ liver) with/without a residual mass; no new lesions; no evidence of FDG-avid disease in BM. CRR: target nodes/nodal masses regressed to ≤ 1.5 cm in LDi;no extralymphatic sites of disease;absent NMLs;organ enlargement regress to normal;no new sites;bone marrow morphology normal. PMR: scores 4 (uptake moderately \> liver), 5 (uptake markedly \> liver, new lesions) with reduced uptake compared with baseline and residual mass; no new lesions; responding disease at interim/residual disease at end of treatment (EOT). PRR: ≥ 50% decrease in sum of the product of perpendicular diameters (SPD) of up to 6 target measurable nodes and extra-nodal sites; absent/normal, regressed, but no increase of NMLs; spleen regressed by \> 50% in length beyond normal; no new sites.

Time frame: First infusion date up to maximum duration of 32.7 months

Duration of Response (DOR) Per the IWG Lugano Classification as Determined by Study Investigators

DOR is defined only for participants who experience an objective response and is the time from the first objective response to disease progression \[progressive metabolic disease (PMD); progressive radiologic disease (PRD)\] or death from any cause. Objective response is defined in outcome measure (OM) 4. PMD: scores 4 (uptake moderately \> liver), 5 (uptake markedly \> liver, new lesions) with increased uptake compared with baseline; new fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma rather than another etiology; new or recurrent FDG-avid foci in bone marrow. PRD: LDi \>1.5 cm; ≥ 50% increase from cross product of LDi and perpendicular diameter (PPD); increase in LDi or shortest axis perpendicular to the LDi (SDi) of 0.5 cm for lesions ≤1.5 cm and 1 cm for lesions \>2 cm; spleen increased by \>50% in length beyond normal; new or recurrent splenomegaly, bone marrow involvement; new lesions; progression of pre-existing lesions. Kaplan-Meier (KM) estimate of median was reported.

Time frame: From the date of first confirmed objective response (CR or PR) to disease progression or death regardless of cause (up to approximately 32.7 months)

Progression-Free Survival (PFS) Per the IWG Lugano Classification as Determined by Study Investigators

PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression (PMD; PRD) or death from any cause. PMD: scores 4 (uptake moderately \> liver), 5 (uptake markedly \> liver, new lesions) with increased uptake compared with baseline; new FDG-avid foci consistent with lymphoma rather than another etiology; new or recurrent FDG-avid foci in bone marrow. PRD: LDi \>1.5 cm; ≥ 50% increase from cross product of LDi and PPD; increase in LDi or SDi of 0.5 cm for lesions ≤1.5 cm and 1 cm for lesions \>2 cm; spleen increased by \>50% in length beyond normal; new or recurrent splenomegaly, bone marrow involvement; new lesions; progression of pre-existing lesions. KM estimate of median was reported.

Time frame: First infusion date up to disease progression or death regardless of cause (up to approximately 32.7 months)

Overall Survival (OS)

OS is defined as the time from axicabtagene ciloleucel infusion to the date of death from any cause. KM estimate of median was reported.

Time frame: First infusion date up to death regardless of cause (up to approximately 32.7 months)

Peak Level of Anti-CD19 CAR T Cells in Blood

Peak was defined as the maximum number of CAR T cells in blood measured after infusion.

Time frame: Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24

Level of Anti-CD19 CAR T Cells in Blood by Visit

Time frame: Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24

Area Under the Curve of CAR T Cells From Day 0 to Day 28 (AUC0-28)

AUC0-28 is defined as the area under curve in a plot of number of CAR T cells against scheduled visit from Day 0 to Day 28.

Time frame: Baseline (Day 0), post-infusion on Days 7, 14, 21, and 28

Time to Peak Level of Anti-CD19 CAR T Cells in Blood

Time to peak was defined as the number of days from the date of the axicabtagene ciloleucel infusion to the date of peak level defined as the maximum number of CAR T cells in blood measured after infusion.

Time frame: Baseline (Day 0), post-infusion on Days 7, 14, 21, 28, 49, 105, 180, Months 9, 12, 15, 18, and 24