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) who have not previously received Bruton's tyrosine kinase inhibitor (BTKi).
Study KTE-C19-102 (NCT02601313) enrolled participants with r/r MCL who had been treated with up to 5 prior regimens, including a BTKi, in Cohorts 1 and 2. To fulfill an FDA postmarketing requirement, Cohort 3 is added to the study. Cohort 3 includes participants with r/r MCL who have been treated with up to five prior regimens but have not received prior therapy with a BTKi. The final analysis for Cohorts 1 and 2 has been completed. Data for Cohort 3 are analyzed separately. Therefore, this separate registration is only for Cohort 3. 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 (NCT05041309).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
95
Administered as intravenous infusion
Administered as intravenous infusion
Administered as intravenous infusion
Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 3
OR: complete metabolic response (CMR),complete radiological response (CRR), partial MR response (PMR),partial RR(PRR).CMR:score 1(no uptake above background)/2(uptake ≤mediastinum)/3(uptake \>mediastinum but ≤liver) with/without a residual mass on positron emission tomography 5-point scale;no new lesions.CRR:target nodes/nodal masses regressed to ≤1.5cm 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;bone marrow normal by morphology. PMR:score 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 the 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.
Time frame: Up to 4 years
Duration of Response (DOR) Per the Lugano Classification According to IRRC in Cohort 3
DOR: time from the first OR to progressive disease (PD)/death. It was determined using Kaplan-Meier (KM) estimates. PD: score 4 (uptake moderately \> liver)/ 5 (uptake markedly \>liver and/or new lesions) with an increase in intensity of uptake from baseline; new fluorodeoxyglucose (FDG)-avid foci consistent with lymphoma at interim/EOT assessment; new FDG-avid foci consistent with lymphoma rather than another etiology; new/recurrent FDG-avid foci in bone marrow; an individual node/lesion must be abnormal with: LDi \> 1.5 cm, increase by ≥ 50% from cross-product of LDi and perpendicular diameter (PPD) nadir, increase in LDi or shortest axis perpendicular to the LDi from nadir, the splenic length must increase by \> 50% of the extent of its prior increase beyond baseline. If no prior splenomegaly, the increase must be ≥ 2 cm from baseline; new/recurrent splenomegaly; new or clear progression of pre-existing NMLs; new lesion; new/recurrent bone marrow involvement.
Time frame: Up to 4 years
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Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
Stanford University
Palo Alto, California, United States
University California Los Angeles (UCLA)
Santa Monica, California, United States
Sarah Cannon- Denver
Denver, Colorado, United States
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Miami, Florida, United States
Moffitt Cancer Center
Tampa, Florida, United States
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Atlanta, Georgia, United States
University of Chicago
Chicago, Illinois, United States
Loyola University Medical Center
Maywood, Illinois, United States
Advocate Aurora Health - Advocate Lutheran General Hospital
Park Ridge, Illinois, United States
...and 30 more locations
Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 3
BOR consisted of complete response (CR), partial response (PR), stable disease (SD), PD, not done and not evaluable (NE). CR=CMR/CRR and PR=PMR/PRR were defined in Outcome Measure (OM) 1. SD/no metabolic response (NMR): a score 4 (uptake moderately greater than (\>) liver) or 5 (uptake markedly \>liver and/ or new lesions) with no significant change in FDG uptake compared to baseline (screening), at an interim time point or end of treatment; no new sites of disease should be observed. PD was defined in OM 2. Not done: no assessment at the time of analysis. Clopper-Pearson method was used for OM analysis. Percentages were rounded off.
Time frame: Up to 4 years
Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 3
OR was defined in OM #1. Percentages were rounded-off.
Time frame: Up to 4 years
Progression Free Survival (PFS) Per the Lugano Classification According to IRRC in Cohort 3
PFS was defined as the time from brexucabtagene autoleucel infusion date to the date of PD or death from any cause. PD was defined in OM #2. Kaplan-Meier (KM) estimates were used for analysis.
Time frame: Up to 4 years
Overall Survival (OS)
OS was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. KM estimates were used for analysis.
Time frame: Up to 4 years
Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participants. The event did not necessarily have a relationship with study treatment. AE included worsening of a pre-existing medical condition. Worsening indicated that the pre-existing medical condition had increased in severity, frequency, and/or duration or had an association with a worse outcome. A pre-existing condition that had not worsened during the study or involved an intervention such as elective cosmetic surgery or a medical procedure while on study, was not considered an AE. TEAE was defined as any AE with onset on or after the start of treatment.
Time frame: Up to 3 years
Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade
Laboratory results were graded according to National Cancer Institute Common Terminology Criteria for Adverse Event (CTCAE) version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.
Time frame: Up to 3 years
Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade
Laboratory results were graded according to National Cancer Institute CTCAE version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.
Time frame: Up to 3 years
Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade
Laboratory results were graded according to National Cancer Institute CTCAE version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.
Time frame: Up to 3 years
Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade
Laboratory results were graded according to National Cancer Institute CTCAE version 4.03. Grade 1 mild, Grade 2 moderate, Grade 3 severe, and Grade 4 life-threatening. Percentages were rounded-off.
Time frame: Up to 3 years
Percentage of Participants With Anti-CD19 CAR Antibodies
Time frame: Baseline up to Month 3
Maximum Number of CAR T Cells Measured Post-infusion
Time frame: Up to Month 36
Peak Serum Levels of C-Reactive Protein (CRP) in Blood
Peak was defined as the maximum post-baseline level of the cytokine.
Time frame: Baseline up to Week 4
Peak Serum Levels of C-X-C Motif Chemokine 10 (CXCL10), Granzyme B, Interferon-gamma (IFN-γ), Interleukin (IL)-1 Receptor Antagonist (RA), IL-2, IL-6, IL-7, IL-8, IL-10, IL-15 and Tumor Necrosis Factor (TNF)-α in Blood
Peak was defined as the maximum post-baseline level of the cytokine.
Time frame: Baseline up to Week 4
Peak Serum Levels of Ferritin, Intercellular Adhesion Molecule (ICAM)-1, IL-2 Receptor Alpha (Rα), Perforin and Vascular Cell Adhesion Molecule (VCAM)-1 in Blood
Peak was defined as the maximum post-baseline level of the cytokine.
Time frame: Baseline up to Week 4
Percentage of Participants With European Quality of Life-5 Dimensions (EQ-5D) Scale Score at Different Timepoints
The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) was a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant was asked for a three-level assessment of their health on the current day: "no problems" (1), "some problems" (2), "extreme problems" (3). EQ-5D health states, defined by the EQ-5D descriptive system, were converted into a single summary index by applying a formula that attaches values (also called QOL weights or QOL utilities) to each of the levels in each dimension. Percentage of participants with each scale score for all 5 dimensions are reported. Percentages were rounded-off.
Time frame: Day 0, Month 18 and Month 24
EQ-5D Visual Analogue Scale (VAS) Score at Different Timepoints
EQ-5D was a standardized participant completed questionnaire that measures health-related quality of life and translated the score into an index value or utility score. EQ-5D-consisted of two components: a health state profile and an optional visual analogue scale (VAS). The EQ-5D-VAS recorded the participant's self-rated health on a vertical visual analogue scale, where the endpoints were labelled 'The best health you can imagine' and 'The worst health you can imagine'. EQ-5D-VAS: range 0 to 100. A higher score indicated better self-reported health status.
Time frame: Day 0, Month 18 and Month 24
Percentage of Participants With Deterioration Scores From Screening in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30
EORTC QLQ-C30 included functional scales (physical, role, cognitive, emotional, and social), global health status/quality of life (QoL) scale, symptom scales (fatigue, pain, nausea/vomiting), and single items scales (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions use 4 point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale (1 'very poor' to 7 'Excellent'). Scores are averaged, transformed to 0-100 scale. Higher scores for functional scales and for the global health status/QoL scale indicate a higher level of functioning and a better health-related QoL, whereas higher scores in symptom scales represent a higher level of symptoms. Deterioration of score was defined as worsened by at least 1 level from screening. Participants with answer "Yes" to the EORTC functional scale questionnaire were reported.
Time frame: Screening Day -28 to Leukapheresis (Day -5), Day 0, Month 18 and Month 24