A Phase 3 Randomized, Open-Label, Multicenter Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Subjects With Relapsed/Refractory Follicular Lymphoma
Overview
- Phase
- Phase 3
- Intervention
- Axicabtagene Ciloleucel
- Conditions
- Relapsed/Refractory Follicular Lymphoma
- Sponsor
- Kite, A Gilead Company
- Enrollment
- 231
- Locations
- 52
- Primary Endpoint
- Progression-free Survival (PFS) as Assessed by Blinded Central Assessment per Lugano Classification
- Status
- Active, not recruiting
- Last Updated
- 6 months ago
Overview
Brief Summary
The goal of this clinical study is test how well the study drug, axicabtagene ciloleucel, works in participants with relapsed/refractory follicular lymphoma
Detailed Description
Five years after the last study participant is randomized, participants who have received axicabtagene ciloleucel will transition to a separate Long-term Follow-up study (study KT-US-982-5968) to complete the remainder of the 15-year follow-up assessments.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically-confirmed follicular lymphoma (FL) (Grade 1, 2, or 3a)
- •Relapsed/refractory (R/r) disease after first-line chemoimmunotherapy and high-risk disease with relapse or progression within 24 months of the initial course of chemoimmunotherapy (ie, POD24), Or r/r disease after ≥ 2 prior systemic lines of therapy
- •Clinical indication for treatment.
- •At least 1 measurable lesion per the Lugano Classification {Cheson 2014}
- •Adequate renal, hepatic, pulmonary, and cardiac function
Exclusion Criteria
- •Presence of large B cell lymphoma or transformed FL
- •Small lymphocytic lymphoma
- •Lymphoplasmacytic lymphoma
- •Full-thickness involvement of the gastric wall by lymphoma
- •FL Grade 3b
- •Prior CD19-targeted therapy
- •Prior CAR therapy or other genetically modified T-cell therapy
- •Uncontrolled fungal, bacterial, viral, or other infection
- •Active Infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus
- •History or presence of a clincially significant central nervous system (CNS) disorder.
Arms & Interventions
Axicabtagene Ciloleucel
Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepleting chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells will be administered.
Intervention: Axicabtagene Ciloleucel
Axicabtagene Ciloleucel
Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepleting chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells will be administered.
Intervention: Cyclophosphamide
Axicabtagene Ciloleucel
Participants will receive cyclophosphamide 500 mg/m\^2/day intravenously (IV) and fludarabine 30 mg/m\^2/day IV lymphodepleting chemotherapy for 3 days followed by axicabtagene ciloleucel administered as a single IV infusion at a target dose of 2 x 10\^6 anti-cluster of differentiation (CD)19 chimeric antigen receptor (CAR) transduced autologous T cells/kg on Day 0. For participants weighing ≥ 100 kg, a maximum flat dose of axicabtagene ciloleucel at 2 x 10\^8 anti-CD19 CAR T cells will be administered.
Intervention: Fludarabine
Standard of Care Therapy
Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus lenalidomide (R\^2) for 12 cycles (28-day cycle) * Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m\^2 on Day 1, Day 8, Day 15, and Day 22 * Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1 * Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21 * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle) * rituximab 375 mg/m\^2 on Day 1 * cyclophosphamide 750 mg/m\^2 on Day 1 * doxorubicin 50 mg/m\^2 on Day 1 * vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * prednisone 40 mg/m\^2 on Day 1 through Day 5 * Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle) * rituximab 375 mg/m\^2 on Day 1 * bendamustine 90 mg/m\^2 on Day 1 and Day 2
Intervention: Cyclophosphamide
Standard of Care Therapy
Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus lenalidomide (R\^2) for 12 cycles (28-day cycle) * Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m\^2 on Day 1, Day 8, Day 15, and Day 22 * Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1 * Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21 * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle) * rituximab 375 mg/m\^2 on Day 1 * cyclophosphamide 750 mg/m\^2 on Day 1 * doxorubicin 50 mg/m\^2 on Day 1 * vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * prednisone 40 mg/m\^2 on Day 1 through Day 5 * Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle) * rituximab 375 mg/m\^2 on Day 1 * bendamustine 90 mg/m\^2 on Day 1 and Day 2
Intervention: Lenalidomide
Standard of Care Therapy
Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus lenalidomide (R\^2) for 12 cycles (28-day cycle) * Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m\^2 on Day 1, Day 8, Day 15, and Day 22 * Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1 * Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21 * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle) * rituximab 375 mg/m\^2 on Day 1 * cyclophosphamide 750 mg/m\^2 on Day 1 * doxorubicin 50 mg/m\^2 on Day 1 * vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * prednisone 40 mg/m\^2 on Day 1 through Day 5 * Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle) * rituximab 375 mg/m\^2 on Day 1 * bendamustine 90 mg/m\^2 on Day 1 and Day 2
Intervention: Rituximab
Standard of Care Therapy
Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus lenalidomide (R\^2) for 12 cycles (28-day cycle) * Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m\^2 on Day 1, Day 8, Day 15, and Day 22 * Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1 * Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21 * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle) * rituximab 375 mg/m\^2 on Day 1 * cyclophosphamide 750 mg/m\^2 on Day 1 * doxorubicin 50 mg/m\^2 on Day 1 * vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * prednisone 40 mg/m\^2 on Day 1 through Day 5 * Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle) * rituximab 375 mg/m\^2 on Day 1 * bendamustine 90 mg/m\^2 on Day 1 and Day 2
Intervention: Doxorubicin
Standard of Care Therapy
Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus lenalidomide (R\^2) for 12 cycles (28-day cycle) * Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m\^2 on Day 1, Day 8, Day 15, and Day 22 * Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1 * Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21 * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle) * rituximab 375 mg/m\^2 on Day 1 * cyclophosphamide 750 mg/m\^2 on Day 1 * doxorubicin 50 mg/m\^2 on Day 1 * vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * prednisone 40 mg/m\^2 on Day 1 through Day 5 * Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle) * rituximab 375 mg/m\^2 on Day 1 * bendamustine 90 mg/m\^2 on Day 1 and Day 2
Intervention: Vincristine
Standard of Care Therapy
Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus lenalidomide (R\^2) for 12 cycles (28-day cycle) * Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m\^2 on Day 1, Day 8, Day 15, and Day 22 * Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1 * Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21 * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle) * rituximab 375 mg/m\^2 on Day 1 * cyclophosphamide 750 mg/m\^2 on Day 1 * doxorubicin 50 mg/m\^2 on Day 1 * vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * prednisone 40 mg/m\^2 on Day 1 through Day 5 * Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle) * rituximab 375 mg/m\^2 on Day 1 * bendamustine 90 mg/m\^2 on Day 1 and Day 2
Intervention: Prednisone
Standard of Care Therapy
Participants will receive the investigator's choice of one of the following therapies/dosing schedules: * Rituximab plus lenalidomide (R\^2) for 12 cycles (28-day cycle) * Cycle 1: lenalidomide 20 mg/day on Day 1 through Day 21; rituximab 375 mg/m\^2 on Day 1, Day 8, Day 15, and Day 22 * Cycle 2 through Cycle 5: lenalidomide 20 mg/day on Day 1 through Day 21; Rituximab 375 mg/m2 on Day 1 * Cycle 6 through Cycle 12: lenalidomide 20 mg/day on Day 1 through Day 21 * Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 6 cycles (21-day cycle) * rituximab 375 mg/m\^2 on Day 1 * cyclophosphamide 750 mg/m\^2 on Day 1 * doxorubicin 50 mg/m\^2 on Day 1 * vincristine 1.4 mg/m\^2 (maximum 2 mg) on Day 1 * prednisone 40 mg/m\^2 on Day 1 through Day 5 * Rituximab plus bendamustine (BR) for 6 cycles (28-day cycle) * rituximab 375 mg/m\^2 on Day 1 * bendamustine 90 mg/m\^2 on Day 1 and Day 2
Intervention: Bendamustine
Outcomes
Primary Outcomes
Progression-free Survival (PFS) as Assessed by Blinded Central Assessment per Lugano Classification
Time Frame: Up to 5 years
PFS is defined as the time from randomization to disease progression or death due to any cause.
Secondary Outcomes
- Event Free Survival (EFS) as Assessed by Blinded Central Assessment per Lugano Classification(Up to 5 years)
- Complete Response (CR) Rate as Assessed by Blinded Central Assessment per Lugano Classification(Up to 5 years)
- Overall Survival (OS)(Up to 5 years)
- Objective Response Rate (ORR) as Assessed by Blinded Central Assessment per Lugano Classification(Up to 5 years)
- Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values(Randomization up to 5 years plus 30 days)
- Percentage of Participants with Replication-competent Retrovirus in Blood Over time(Up to 5 years)
- Duration of Response (DOR) as Assessed by Blinded Central Assessment per Lugano Classification(Up to 5 years)
- Duration of CR as Assessed by Blinded Central Assessment per Lugano Classification(Up to 5 years)
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)(Randomization up to 5 years plus 30 days)
- Change From Baseline in the Global Health Status Quality of Life Scale of the European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire-30 (EORTC QLQ-C30)(Baseline, up to 5 years)
- Change From Baseline in the Physical Functioning Domain of the EORTC QLQ-C30(Baseline, up to 5 years)
- Change From Baseline in the Global Health Status Quality of Life Scale of the Low Grade Non-Hodgkin Lymphoma-20 (NHL-LG20)(Baseline, up to 5 years)
- Change From Baseline in the Physical Functioning Domain of the NHL-LG20(Baseline, up to 5 years)
- Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L)(Baseline, up to 5 years)
- Time to Next Treatment (TTNT)(Up to 5 years)
- Changes From Baseline in the Visual Analog Scale (VAS) Scores(Baseline, up to 5 years)