Relapsed/Refractory Follicular Lymphoma
Conditions
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.
Interventions
BIOLOGICALAxicabtagene Ciloleucel
A single infusion of chimeric antigen receptor (CAR)-transduced autologous T cells
DRUGCyclophosphamide
Administered intravenously
DRUGFludarabine
Administered intravenously
DRUGLenalidomide
Administered orally
DRUGRituximab
Administered intravenously
DRUGDoxorubicin
Administered intravenously
DRUGVincristine
Administered intravenously
DRUGPrednisone
Administered orally
DRUGBendamustine
Administered intravenously
Sponsors
Kite, A Gilead Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key 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 Key
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. * 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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) | Randomization up to 5 years plus 30 days | — |
| Overall Survival (OS) | Up to 5 years | OS is defined as the time from randomization to death from any cause. |
| Percentage of Participants with Replication-competent Retrovirus in Blood Over time | Up to 5 years | — |
| 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. |
| 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. |
| Percentage of Participants Experiencing Clinically Significant Changes in Safety Laboratory Values | Randomization up to 5 years plus 30 days | — |
Countries
France, Germany, Italy, Japan, Spain, United Kingdom, United States
Outcome results
None listed