Study of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Participants With Relapsed/Refractory Follicular Lymphoma
- Conditions
- Relapsed/Refractory Follicular Lymphoma
- Interventions
- Registration Number
- NCT05371093
- Lead Sponsor
- Kite, A Gilead Company
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 230
- 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
Key
- 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.
- History of autoimmune disease
- Known history or CNS lymphoma involvement
- Cardiac lymphoma involvement
- History of clinically significant cardiac disease 6 months before randomization
- Neuropathy greater than grade 2
- Females who are pregnant or breastfeeding
- Individuals of both genders who are not willing to practice birth control
- Presence of any indwelling line or drain (eg, percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, G/J-tube, pleural/peritoneal/pericardial catheter, or Ommaya reservoirs). Dedicated central venous access catheters such as Port-a-Cath or Hickman catheter are permitted.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 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. Axicabtagene Ciloleucel Cyclophosphamide 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. Axicabtagene Ciloleucel Fludarabine 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. Standard of Care Therapy Lenalidomide 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 Standard of Care Therapy Cyclophosphamide 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 Standard of Care Therapy Vincristine 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 Standard of Care Therapy Rituximab 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 Standard of Care Therapy Bendamustine 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 Standard of Care Therapy Doxorubicin 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 Standard of Care Therapy Prednisone 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
- Primary Outcome Measures
Name Time Method Progression-free Survival (PFS) as Assessed by Blinded Central Assessment per Lugano Classification Up to 5 years PFS is defined as the time from randomization to disease progression or death due to any cause.
- Secondary Outcome Measures
Name Time Method Event Free Survival (EFS) as Assessed by Blinded Central Assessment per Lugano Classification Up to 5 years EFS is defined as the time from randomization to the earliest date of disease progression, the initiation of subsequent off-protocol anti-FL therapy, or death from any cause.
Overall Survival (OS) Up to 5 years OS is defined as the time from randomization to death from any cause.
Objective Response Rate (ORR) as Assessed by Blinded Central Assessment per Lugano Classification Up to 5 years Objective response rate is defined as the proportion of participants with best overall response of either a complete response or a partial response during the study prior to any subsequent off-protocol anti-FL therapy.
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 Complete Response (CR) Rate as Assessed by Blinded Central Assessment per Lugano Classification Up to 5 years CR rate is defined as the proportion of participants with best overall response of CR during the study prior to any subsequent off-protocol anti-follicular lymphoma (FL) therapy.
Duration of Response (DOR) as Assessed by Blinded Central Assessment per Lugano Classification Up to 5 years DOR is defined as the time from first objective response to disease progression or death from any cause.
Duration of CR as Assessed by Blinded Central Assessment per Lugano Classification Up to 5 years Duration of CR is defined as the time from first CR to disease progression or death from any cause.
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 The EORTC-QLQ-C30 is a multi-item questionnaire measuring the following content five (5) multi-item functional scales, three (3) multi-item symptom scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL) each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.
Change From Baseline in the Physical Functioning Domain of the EORTC QLQ-C30 Baseline, up to 5 years The EORTC-QLQ-C30) is a multi-item questionnaire measuring the following content five (5) multi-item functional scales, three (3) multi-item symptom scales, one (1) global health status scale, and one (1) global health-related quality of life (HRQoL) each scale is measured from 0 to 100 after a linear transformation. Higher scores for functioning scales and for the Global Health Status or Global HRQoL scales indicate a higher level of functioning and a better HRQoL respectively, whereas higher scores in symptom scales represent a higher level of symptoms.
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 The NHL-LG20 is is a 20-item supplement questionnaire that was specifically developed to assess HRQoL in participants with low-grade non-Hodgkin lymphomas (such as follicular lymphoma). The NHL-LG20 includes multi-item scales of symptom burden, physical condition/fatigue, worries/fears on health and functioning, and emotional impact; and is administered in conjunction with the EORTC QLQ-C30. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales and for the global health status or global HRQoL scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.
Change From Baseline in the Physical Functioning Domain of the NHL-LG20 Baseline, up to 5 years The NHL-LG20 is is a 20-item supplement questionnaire that was specifically developed to assess HRQoL in participants with low-grade non-Hodgkin lymphomas (such as follicular lymphoma). The NHL-LG20 includes multi-item scales of symptom burden, physical condition/fatigue, worries/fears on health and functioning, and emotional impact; and is administered in conjunction with the EORTC QLQ-C30. Each scale is measured from 0 to 100 after a linear transformation. Higher scores for functional scales and for the global health status or global HRQoL scales indicate a higher level of functioning and a better HRQoL, whereas higher scores in symptom scales represent a higher level of symptoms.
Changes From Baseline in the European Quality of Life Five Dimensions Five Levels Scale (EQ-5D-5L) Baseline, up to 5 years The EQ-5D-5L questionnaire is a generic measure of health status that provides a simple descriptive profile and a single index value. The EQ-5D-5L comprises 2 components: a questionnaire covering 5 dimensions and a tariff of values based upon direct valuations of health states using a visual analog scale (VAS). Rating gets recorded on a vertical VAS in which the endpoints are labeled best imaginable health state is 100 (on the top) and worst imaginable health state is 0 (on the bottom). Higher scores of EQ VAS indicate better health.
Time to Next Treatment (TTNT) Up to 5 years TTNT is defined as the time from randomization to the start of subsequent off-protocol anti-lymphoma therapy or death from any cause.
Changes From Baseline in the Visual Analog Scale (VAS) Scores Baseline, up to 5 years The EQ-5D-5L VAS is a 20-cm VAS for recording self-rated current HRQoL state and is used to describe the participants health status on the day of the assessment. The EQ-5D-5L VAS score is recorded by each participant for his or her current HRQoL state and scored 0 ("the worst health you can imagine") to 100 ("the best health you can imagine"). Higher scores indicate better health.
Trial Locations
- Locations (52)
Institut Paoli-Calmettes
🇫🇷Marseille, France
Hopital Saint Eloi
🇫🇷Montpellier, France
Hopital Pitie-Salpetriere
🇫🇷Paris, France
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
🇺🇸Duarte, California, United States
Stanford Health Care
🇺🇸Stanford, California, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
The University of Kansas Hospital
🇺🇸Westwood, Kansas, United States
University of Maryland Greenebaum Comprehensive Cancer Center
🇺🇸Baltimore, Maryland, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Novant Health Cancer Institute Hematology - Charlotte
🇺🇸Charlotte, North Carolina, United States
Penn State Milton S. Hershey Medical Center
🇺🇸Hershey, Pennsylvania, United States
TriStar Centennial Medical Center - Cell Processing
🇺🇸Nashville, Tennessee, United States
Henry-Joyce Cancer Clinic
🇺🇸Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Hopital Henri Mondor
🇫🇷Créteil, France
CHU de Dijon
🇫🇷Dijon, France
Hôpital Claude Huriez-CHU de Lille
🇫🇷Lille cedex, France
CHU Bordeaux - Hospital Haut-Leveque - Centre Francois Magendie
🇫🇷Pessac, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre Benite, France
CHU de Poitiers
🇫🇷Poitiers, France
Hopital Pontchaillou - CHU Rennes
🇫🇷Rennes, France
Centre Henri Becquerel
🇫🇷Rouen, France
Universitatsmedizin Gottingen
🇩🇪Göttingen, Germany
Universitatsklinikum Koln Klinik I fur Innere Medizin
🇩🇪Wuerzburg, Germany
ASST Papa Giovanni XXIII
🇮🇹Bergamo, Italy
Azienda Ospedallero-Universitaria di Bologna Policlinico Sant'Orsola-Malpighi
🇮🇹Bologna, Italy
Fondazione IRCCS - Istituto Nazionale Tumori
🇮🇹Milano, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
Istituto Clinico Humanitas-IRCCS
🇮🇹Rozzano, Italy
Hyogo Medical University Hospital
🇯🇵Hyogo, Japan
University Hospital Kyoto Prefectural University of Medicine
🇯🇵Kyoto, Japan
Tohoku University Hospital
🇯🇵Miyagi, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Hospital Universitari Vall d'Hebrón
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Instituto Catalan de Oncologia - Hospital Duran i Reynolds (ICO L'Hospitalet)
🇪🇸Barcelona, Spain
University Hospital Birmingham NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Cambridge University Hospitals NHS Foundation Trust
🇬🇧Cambridge, United Kingdom
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Oxford University Hospitals NHS Foundation Trust
🇬🇧Oxford, United Kingdom
The University Hospital Southampton NHS Foundation Trust
🇬🇧Southampton, United Kingdom
The Royal Marsden NHS Foundation Trust
🇬🇧Sutton, United Kingdom