Clinical Trials /

Study to Evaluate the Efficacy of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma

NCT02601313

Description:

The primary objective of the study is to evaluate the efficacy of brexucabtagene autoleucel (KTE-X19) in participants with relapsed/refractory mantle cell lymphoma (MCL)

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study to Evaluate the Efficacy of Brexucabtagene Autoleucel (KTE-X19) in Participants With Relapsed/Refractory Mantle Cell Lymphoma
  • Official Title: A Phase 2 Multicenter Study Evaluating the Efficacy of KTE-X19 in Subjects With Relapsed/Refractory Mantle Cell Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: KTE-C19-102
  • SECONDARY ID: 2015-005008-27
  • NCT ID: NCT02601313

Conditions

  • Relapsed/Refractory Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
brexucabtagene autoleucelKTE-X19, TECARTUSAxicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19)
CyclophosphamideAxicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19)
FludarabineAxicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19)
Axicabtagene CiloleucelAxicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19)

Purpose

The primary objective of the study is to evaluate the efficacy of brexucabtagene autoleucel (KTE-X19) in participants with relapsed/refractory 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.
    

Trial Arms

NameTypeDescriptionInterventions
Axicabtagene ciloleucel/brexucabtagene autoleucel (KTE-X19)ExperimentalParticipants with relapsed/refractory mantle cell lymphoma (MCL) will receive conditioning chemotherapy (CTE) 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 axicabtagene ciloleucel at a targeted dose of 2 x 10^6 anti-CD19 chimeric antigen receptor (CAR) T cells/kg on Day 0 or brexucabtagene autoleucel (KTE-X19) at a targeted dose of 2 x 10^6 CAR T cells/kg, with a maximum dose of 2 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 1 or brexucabtagene autoleucel at a targeted dose of 0.5 x 10^6 anti-CD19 CAR T cells/kg, with a maximum dose of 0.5 x 10^8 anti-CD19 CAR T cells for participants ≥ 100 kg on Day 0 in Cohort 2.
  • brexucabtagene autoleucel
  • Cyclophosphamide
  • Fludarabine
  • Axicabtagene Ciloleucel

Eligibility 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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With Objective Response (OR) Per the Lugano Classification According to Independent Radiology Review Committee (IRRC) in Cohort 1
Time Frame:Up to 2 years
Safety Issue:
Description: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 ≤ 1.5 cm 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 Outcome Measures

Measure:Duration of Response (DOR) in Cohort 1
Time Frame:Up to 15 years
Safety Issue:
Description:DOR: time from the first OR to progressive disease (PD)/death. It is 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.
Measure:Duration of Response (DOR) in Cohort 2
Time Frame:Up to 15 years
Safety Issue:
Description:DOR: time from the first OR to PD/death. It is determined using 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 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 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.
Measure:Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by International Working Group (IWG) 2007 Criteria in Cohort 1
Time Frame:Up to 15 years
Safety Issue:
Description:BOR consists of (Complete response [CR], Partial response [PR], stable disease [SD], progressive disease [PD] and unknown). CR: disappearance of all detectable clinical evidence; PR: 50% decrease in the sum of the product of diameters (SPD) of up to 6 largest dominant nodal masses and >= 50% decrease in SPD of spleen/liver nodules; PD: appearance of any new lesions or >= 50% increase in SPD of more than one node or >= 50% increase in longest diameter of a previously identified node or >50% increase from nadir in the SPD of any previous lesions; SD: failure to attain CR/PR or PD.
Measure:Percentage of Participants With Best Objective Response (BOR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 2
Time Frame:Up to 15 years
Safety Issue:
Description:BOR consists of CR (CMR/CRR), PR (PMR/PRR), SD, PD and not done. CMR/CRR and PMR/PRR are defined in Outcome Measure (OM) 1. PD is defined in OM 3. 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.Not done: no assessment at the time of analysis.
Measure:Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by International Working Group (IWG) 2007 Criteria in Cohort 1
Time Frame:Up to 15 years
Safety Issue:
Description:OR: CR or PR. CR: disappearance of all detectable clinical evidence; typically FDG-avid lymphoma (a post-treatment residual mass of any size is permitted if it is PET negative); variably FDG-avid lymphomas/FDG avidity unknown (all lymph nodes and nodal masses must have regressed to normal size); spleen and/or liver should be normal size and not be palpable; bone marrow aspirate and biopsy must show no evidence of disease. PR: 50% decrease in the SPD of up to 6 largest dominant nodal masses and ≥ 50% decrease in SPD of spleen/liver nodules; no increase in size of nodes, liver, or spleen and no new sites of disease; splenic and hepatic nodules must regress by ≥ 50% in the SPD; if participant has persistent bone marrow involvement and otherwise meets criteria for CR, will then be considered a PR; typically FDG-avid lymphoma (the post-treatment PET scan should be positive in at least 1 previously involved site.
Measure:Percentage of Participants With Objective Response (OR) as Per Investigator Assessment Determined by Lugano Classification in Cohort 2
Time Frame:Up to 15 years
Safety Issue:
Description:OR: CMR, CRR, PMR, 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 ≤ 1.5 cm in LDi ;no extralymphatic sites of disease;absent 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 EOT. PRR: ≥ 50% decrease in 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.
Measure:Progression Free Survival (PFS) in Cohort 1
Time Frame:Up to 15 years
Safety Issue:
Description:PFS was defined as the time from the brexucabtagene autoleucel infusion date to the date of PD or death from any cause. PD: a score 4 (uptake moderately > liver) or 5 (uptake markedly >liver and/or new lesions) with an increase in intensity of uptake from baseline; new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment; new FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection, inflammation); new or recurrent FDG-avid foci in bone marrow. PFS was determined using the KM estimates.
Measure:Progression Free Survival (PFS) in Cohort 2
Time Frame:Up to 15 years
Safety Issue:
Description:PFS was defined as the time from the brexucabtagene autoleucel infusion date to the date of PD or death from any cause. PD: a score 4 (uptake moderately > liver) or 5 (uptake markedly >liver and/or new lesions) with an increase in intensity of uptake from baseline; new FDG-avid foci consistent with lymphoma at interim or end of treatment assessment; new FDG-avid foci consistent with lymphoma rather than another etiology (eg, infection, inflammation); new or recurrent FDG-avid foci in bone marrow. PFS was determined using the KM estimates.
Measure:Overall Survival in Cohort 1
Time Frame:Up to 15 years
Safety Issue:
Description:Overall survival was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. Overall survival was determined using the KM estimates.
Measure:Overall Survival in Cohort 2
Time Frame:Up to 15 years
Safety Issue:
Description:Overall survival was defined as the time from brexucabtagene autoleucel infusion to the date of death from any cause. Overall survival was determined using the KM estimates.
Measure:Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Hematology Toxicity Values by Worst Toxicity Grade
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Percentage of Participants With Decrease in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Percentage of Participants With Increase in Post-brexucabtagene Autoleucel Infusion Chemistry Toxicity Values by Worst Toxicity Grade
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Percentage of Participants With Anti-CD19 CAR Antibodies
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Peak Anti-CD19 CAR T-Cell (Brexucabtagene Autoleucel) Level (Maximum Observed Plasma Concentration) in Blood
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Peak Serum Levels of C-Reactive Protein (CRP) in Blood
Time Frame:Up to 15 years
Safety Issue:
Description:
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
Time Frame:Up to 15 years
Safety Issue:
Description:
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
Time Frame:Up to 15 years
Safety Issue:
Description:
Measure:Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Mobility Scale Score
Time Frame:Baseline, Week 4, Month 3, and Month 6
Safety Issue:
Description: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. The percentage of participants with each level of problem are reported.
Measure:Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Self-Care Scale Score
Time Frame:Baseline, Week 4, Month 3, and Month 6
Safety Issue:
Description: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. The percentage of participants with each level of problem are reported.
Measure:Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Usual Activity Scale Score
Time Frame:Baseline, Week 4, Month 3, and Month 6
Safety Issue:
Description: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. The percentage of participants with each level of problem are reported.
Measure:Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Pain / Discomfort Activity Scale Score
Time Frame:Baseline, Week 4, Month 3, and Month 6
Safety Issue:
Description: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. The percentage of participants with each level of problem are reported.
Measure:Change Over Time in European Quality of Life-5 Dimensions(EQ-5D) Anxiety / Depression Activity Scale Score
Time Frame:Baseline, Week 4, Month 3, and Month 6
Safety Issue:
Description: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. The Percentage of participants with each level of problem are reported.
Measure:Change Over Time in EQ-5D Visual Analogue Scale (VAS) Score
Time Frame:Baseline, Week 4, Month 3, and Month 6
Safety Issue:
Description: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. A positive change indicates an improvement.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Kite, A Gilead Company

Last Updated

July 23, 2021