Clinical trial NCT02601313: Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 1 and Cohort 2)
Official title: A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects With Relapsed/Refractory Mantle Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsed/Refractory Mantle Cell Lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2015-11-10
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical study is to test how well the study drug, brexucabtagene autoleucel (KTE-X19), works in participants with relapsed/refractory (r/r) mantle cell lymphoma (MCL).

Detailed description: Study KTE-C19-102 enrolled participants with r/r MCL who have been treated with up to 5 prior regimens including a Bruton's tyrosine kinase inhibitor (BTKi) in Cohort 1 and Cohort 2. However, to fulfill FDA Postmarketing Requirement, Cohort 3 is added to the study. It will include participants with r/r MCL who have been treated with up to 5 prior regimens but have not received prior therapy with a BTKi.

The primary analysis in Cohort 1 and Cohort 2 is already completed. Data for Cohort 3 will be analyzed separately. Therefore, details for Cohort 3 were registered separately (NCT04880434) on ClinicalTrials.gov as this cohort will not be part of the main study analysis.

After the end of KTE-C19-102, subjects who received an infusion of anti-CD19 CAR T cells will complete the remainder of the 15-year follow-up assessments in a separate long-term follow-up study, KT-US-982-5968

Eligibility criteria: Key Inclusion Criteria:

Up to 5 prior regimens for Mantle cell lymphoma. Prior therapy must have included:

* Anthracycline or bendamustine-containing chemotherapy and
* Anti-CD20 monoclonal antibody therapy and
* Ibrutinib or acalabrutinib

At least 1 measurable lesion

Platelet count ≥ 75,000/uL

Creatinine clearance (as estimated by Cockcroft Gault) \> or = to 60 mL/min

Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings

Baseline oxygen saturation \>92% on room air.

Key Exclusion Criteria:

* Known history of infection with human immunodeficiency virus (HIV) or hepatitis B (HBsAG positive) or hepatitis C virus (anti-HCV positive). A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per standard serological and genetic testing
* History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, posterior reversible encephalopathy syndrome, or any autoimmune disease with central nervous system (CNS) involvement
* Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 1
timeFrame: Up to 7.8 years
measure: Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 2
timeFrame: Up to 7.8 years
Secondary outcomes:
measure: Duration of Response (DOR) in Cohort 1 as Per Investigator Response
timeFrame: Up to 7.8 years
measure: Duration of Response (DOR) in Cohort 2 as Per Investigator Response
timeFrame: Up to 7.8 years
measure: Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by International Working Group (IWG) 2007 Criteria in Cohort 1
timeFrame: Up to 7.8 years
measure: Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 2
timeFrame: Up to 7.8 years
measure: Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by International Working Group (IWG) 2007 Criteria in Cohort 1
timeFrame: Up to 7.8 years
measure: Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 2
timeFrame: Up to 7.8 years
measure: Progression Free Survival (PFS) in Cohort 1 as Per Investigator Response.
timeFrame: Up to 7.8 years
measure: Progression Free Survival (PFS) in Cohort 2 as Per Investigator Response.
timeFrame: Up to 7.8 years
measure: Overall Survival in Cohort 1
timeFrame: Up to 7.8 years
measure: Overall Survival in Cohort 2
timeFrame: Up to 7.8 years
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAE)
timeFrame: Up to 5 years
measure: Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade
timeFrame: Up to 5 years
measure: Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade
timeFrame: Up to 5 years
measure: Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade
timeFrame: Up to 5 years
measure: Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade
timeFrame: Up to 5 years
measure: Percentage of Participants With Anti-CD19 CAR Antibodies
timeFrame: Baseline up to Month 3
measure: Maximum Number of CAR T Cells Measured Post-infusion
timeFrame: Up to Month 24
measure: Peak Serum Levels of C-Reactive Protein (CRP) in Blood
timeFrame: Baseline up to Week 4
measure: Peak Serum Levels of C-X-C Motif Chemokine 10 (CXCL10), Granzyme B, Interferon-Gamma (IFN-γ), Interleukin-1 Receptor Antagonist (IL-1RA), Interleukin (IL)-2, IL-6, IL-7, IL-8,IL-10, IL-15, and Tumor Necrosis Factor-Alpha (TNF-α) in Blood
timeFrame: Baseline up to Week 4
measure: Peak Serum Levels of Ferritin, Interleukin-2 Receptor Alpha (IL-2Rα), Intercellular Adhesion Molecule-1 (ICAM-1), Perforin, Vascular Cell Adhesion Molecule-1 (VCAM-1) in Blood
timeFrame: Baseline up to Week 4
measure: Percentage of Participants With Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Mobility Scale Score
timeFrame: Baseline, Week 4, Month 3, and Month 6
measure: Percentage of Participants With Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Self-Care Scale Score
timeFrame: Baseline, Week 4, Month 3, and Month 6
measure: Percentage of Participants With Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Usual Activity Scale Score
timeFrame: Baseline, Week 4, Month 3, and Month 6
measure: Percentage of Participants With Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Pain / Discomfort Activity Scale Score
timeFrame: Baseline, Week 4, Month 3, and Month 6
measure: Percentage of Participants With Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Anxiety / Depression Activity Scale Score
timeFrame: Baseline, Week 4, Month 3, and Month 6
measure: Change Over Time in EQ-5D Visual Analogue Scale (VAS) Score
timeFrame: Baseline, Week 4, Month 3, and Month 6
Other outcomes:
Locations:
city: Gilbert
country: United States
facility: Banner MD Anderson
state: Arizona
city: Duarte
country: United States
facility: City of Hope
state: California
city: Santa Monica
country: United States
facility: University California Los Angeles (UCLA)
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Denver
country: United States
facility: Sarah Cannon
state: Colorado
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University Chicago
state: Illinois
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Portland
country: United States
facility: Robert W. Franz Cancer Research Center
state: Oregon
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Dallas
country: United States
facility: Baylor Charles A. Sammons Cancer Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Bordeaux
country: France
facility: Centre Hospitalier Universitaire (CHU)
city: Paris
country: France
facility: Hospital Saint Louis
city: Pessac
country: France
facility: Hopital Haut-Leveque
city: Dresden
country: Germany
facility: Universitätsklinik Dresden
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
affiliation: Kite, A Gilead Company
name: Kite Study Director
role: STUDY_DIRECTOR
References:
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