Relapsed/Refractory Mantle Cell Lymphoma
Conditions
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 (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
Interventions
DRUGFludarabine
Administered intravenously
DRUGCyclophosphamide
Administered intravenously
BIOLOGICALBrexucabtagene autoleucel
A single infusion of brexucabtagene autoleucel (KTE-X19) anti-CD 19 CAR T cells
Sponsors
Kite, A Gilead Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Per Lugano Classification as Determined by the Independent Radiology Review Committee (IRRC) | Up to 4 years | ORR is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification as determined by IRRC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Best Objective Response (BOR) | Up to 4 years | 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. |
| Objective Response Rate (ORR) per Lugano Classification as Determined by Investigators | Up to 4 years | ORR, as determined by investigators, is defined as the incidence of either a complete response (CR) or partial response (PR) per the Lugano Classification. |
| Progression Free Survival (PFS) | Up to 4 years | — |
| Overall Survival | Up to 4 years | — |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events | Up to 4 years | — |
| Percentage of Participants With Clinically Significant Changes in Laboratory Values | Up to 4 years | — |
| Duration of Response (DOR) | Up to 4 years | DOR is defined as the time from their first objective response to disease progression or death. |
| Levels of Anti-CD19 CAR T Cells in Blood | Up to 4 years | — |
| Levels of Cytokines in Serum | Up to 4 years | — |
| Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Scale Score | Baseline and up to 24 months | 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. |
| Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Visual Analogue Scale (VAS) Score | Baseline and up to 24 months | 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. |
| Changes in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) Score from Baseline Over Time | Baseline and up to 6 months | 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. |
| Percentage of Participants Who Develop Anti-CD19 CAR Antibodies | Up to 4 years | — |
Countries
France, Germany, Netherlands, Spain, United Kingdom, United States
Outcome results
None listed