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) who have not previously received Bruton's tyrosine kinase inhibitor (BTKi).
Detailed description
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).
Interventions
DRUGFludarabine
Administered as intravenous infusion
DRUGCyclophosphamide
Administered as intravenous infusion
BIOLOGICALBrexucabtagene autoleucel
Administered as intravenous infusion
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 mantle cell lymphoma (MCL). Prior therapy must have included anthracycline- or bendamustine-containing chemotherapy and anti-cluster of differentiation 20 (CD20) monoclonal antibody therapy. Individuals must not have received prior therapy with a Bruton's tyrosine kinase inhibitor (BTKi). * At least 1 measurable lesion * Platelet count ≥ 75,000/μL * 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 anti-hepatitis C virus (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 |
|---|---|---|
| Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 3 | Up to 4 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Per the Lugano Classification According to IRRC in Cohort 3 | Up to 4 years | 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. |
| Overall Survival (OS) | Up to 4 years | OS was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. KM estimates were used for analysis. |
| Duration of Response (DOR) Per the Lugano Classification According to IRRC in Cohort 3 | Up to 4 years | 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. |
| Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 3 | Up to 4 years | 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. |
| Percentage of Participants Experiencing Treatment-Emergent Adverse Events (TEAEs) | Up to 3 years | 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. |
| Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade | Up to 3 years | 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. |
| Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade | Up to 3 years | 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. |
| Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade | Up to 3 years | 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. |
| Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade | Up to 3 years | 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. |
| Percentage of Participants With Anti-CD19 CAR Antibodies | Baseline up to Month 3 | — |
| Maximum Number of CAR T Cells Measured Post-infusion | Up to Month 36 | — |
| Peak Serum Levels of C-Reactive Protein (CRP) in Blood | Baseline up to Week 4 | Peak was defined as the maximum post-baseline level of the cytokine. |
| 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 | Baseline up to Week 4 | Peak was defined as the maximum post-baseline level of the cytokine. |
| 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 | Baseline up to Week 4 | Peak was defined as the maximum post-baseline level of the cytokine. |
| Percentage of Participants With European Quality of Life-5 Dimensions (EQ-5D) Scale Score at Different Timepoints | Day 0, Month 18 and Month 24 | 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. |
| EQ-5D Visual Analogue Scale (VAS) Score at Different Timepoints | Day 0, Month 18 and Month 24 | 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. |
| Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 3 | Up to 4 years | OR was defined in OM #1. Percentages were rounded-off. |
| 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 | Screening Day -28 to Leukapheresis (Day -5), Day 0, Month 18 and Month 24 | 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. |
Countries
France, Germany, Netherlands, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORKite Study Director
Kite, A Gilead Company
Participant flow
Recruitment details
Participants were enrolled at study sites in France, Germany, Netherlands, Spain, the United Kingdom, and the United States.
Pre-assignment details
Out of 254 participants screened for the overall KTE-C19-102 study, 95 participants were enrolled for Cohort 3 of this study. Results for KTE-C19-102, Cohorts 1 and 2 were reported in NCT02601313, and results for Cohort 3 (NCT04880434) are reported in this study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 42 Participants |
| Age, Categorical Between 18 and 65 years | 44 Participants |
| Age, Continuous | 64.0 years STANDARD_DEVIATION 8.6 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 4 Participants |
| Race/Ethnicity, Customized Ethnicity Not Collected | 5 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 77 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants |
| Race/Ethnicity, Customized Race Not Collected | 5 Participants |
| Race/Ethnicity, Customized Race Other or More Than One Race | 2 Participants |
| Race/Ethnicity, Customized Race White | 78 Participants |
| Region of Enrollment France | 9 Participants |
| Region of Enrollment Germany | 9 Participants |
| Region of Enrollment Netherlands | 27 Participants |
| Region of Enrollment Spain | 12 Participants |
| Region of Enrollment United Kingdom | 1 Participants |
| Region of Enrollment United States | 28 Participants |
| Sex: Female, Male Female | 19 Participants |
| Sex: Female, Male Male | 67 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 22 / 95 | 1 / 1 |
| other Total, other adverse events | 86 / 86 | 1 / 1 |
| serious Total, serious adverse events | 56 / 86 | 1 / 1 |
Outcome results
None listed