Study of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma (Cohort 3)

Study Overview
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Brief Summary
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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
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Study KTE-C19-102 (NCT02601313) 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, 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

Official Title
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A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects With Relapsed/Refractory Mantle Cell Lymphoma

Conditions
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Relapsed/Refractory Mantle Cell Lymphoma

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Cyclophosphamide
* Biological: Brexucabtagene autoleucel


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Up to 5 prior regimens for MCL. Prior therapy must have included anthracycline- or bendamustine-containing chemotherapy and anti-CD20 monoclonal antibody therapy. Individuals must not have received prior therapy with a BTKi. At least 1 measurable lesion Platelet count ≥ 75,000/uL Creatinine clearance (as estimated by Cockcroft Gault) ≥ to 60 cc/min Cardiac ejection fraction ≥ 50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO) or multigated acquisition (MUGA), 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). Individuals with a history of hepatitis infection must have cleared their infection as determined by 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brexucabtagene autoleucel (KTE-X19)<br>Participants with relapsed/refractory mantle cell lymphoma will receive conditioning chemotherapy consisting of fludarabine 30 mg/m^2/day and cyclophosphamide 500 mg/m^2/day intravenous (IV) infusion for 3 days followed by a single infusion of brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg, with a maximum flat dose of 2 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 3. | Drug: Fludarabine<br>* Administered intravenously<br>Drug: Cyclophosphamide<br>* Administered intravenously<br>Biological: Brexucabtagene autoleucel<br>* A single infusion of brexucabtagene autoleucel (KTE-X19) anti-CD 19 CAR T cells<br>* Other names: TECARTUS™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) Per Lugano Classification as Determined by the Independent Radiology Review Committee (IRRC) | ORR is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification as determined by IRRC. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DOR is defined as the time from their first objective response to disease progression or death. | Up to 7 years | 
| Percentage of Participants With Best Objective Response (BOR) | Best objective response is defined as the incidence of complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD), or unevaluable as best response to treatment. | Up to 7 years | 
| Objective Response Rate (ORR) per Lugano Classification as Determined by Investigators | ORR, as determined by investigators, is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification. | Up to 7 years | 
| Progression Free Survival (PFS) |  | Up to 7 years | 
| Overall Survival |  | Up to 7 years | 
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events |  | Up to 7 years | 
| Percentage of Participants With Clinically Significant Changes in Laboratory Values |  | Up to 7 years | 
| Percentage of Participants Who Develop Anti-CD19 CAR Antibodies |  | Up to 7 years | 
| Levels of Anti-CD19 CAR T Cells in Blood |  | Up to 7 years | 
| Levels of Cytokines in Serum |  | Up to 7 years | 
| Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Scale Score | The European Quality of Life-5 Dimensions Health Questionnaire (EQ-5D) is a participant-answered questionnaire scoring 5 dimensions of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. For each dimension the participant is 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, are 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. EQ-5D Summary Index values range from -0.11 (worst health state) to 1.00 (perfect health state). Positive numbers indicate improvement from baseline. | Baseline and up to 24 months | 
| Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Visual Analogue Scale (VAS) Score | EQ-5D is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-consists of two components: a health state profile and an optional visual analogue scale (VAS). The EQ5D-VAS records the participant's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. EQ-5D-VAS: range 0 to 100. A higher score indicates better self-reported health status. | Baseline and up to 24 months | 
| Changes in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score from Baseline Over Time | EORTC QLQ-C30 includes functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting), and single items (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 score indicate high QoL. A positive change from baseline indicates better quality of life. | Baseline and up to 6 months |