Schéma : This study will enroll approximately 160 adult subjects who have relapsed or refractory (r/r) iNHL to be infused with the study treatment, axicabtagene ciloleucel, to see if their disease responds to this experimental product and if this product is safe. Axicabtagene ciloleucel is made from the subjects own white blood cells which are genetically modified and grown to fight cancer. An objective response rate of 70% is targeted.
All enrolled subjects will be screened for eligibility then will undergo leukapheresis to collect white blood cells for manufacturing. In preparation for the infusion with axicabtagene ciloleucel, subjects will undergo conditioning chemotherapy with cyclophosphamide and fludarabine for 3 days to help the study treatment be effective. After the product is manufactured and conditioning chemotherapy period is complete, subjects will be infused with axicabtagene ciloleucel and then monitored in a hospital for a minimum of 7 days. Subjects will be followed by their study doctor for continued monitoring of the safety and effectiveness of the study treatment for approximately 3 months after receiving treatment and then will be followed for safety for up to an additional 15 years.
- Biological: axicabtagene ciloleucel
A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
Other Name: Yescarta®
- Drug: Cyclophosphamide
- Drug: Fludarabine
Current Primary Outcome Measures:
Objective response rate per central read [ Time Frame: Up to 15 years ]
Complete response (CR) + partial response (PR) per the Lugano Classiciation (Cheson et al, 2014).
Original Primary Outcome Measures:
Objective response rate [ Time Frame: 6 months ]
Complete response (CR) + partial response (PR) per the revised International Working Group (IWG) Response Criteria for Malignant Lymphoma (Cheson 2007) as determined by the study investigators.
Current Secondary Outcome Measures:
- CR Rate per central read [ Time Frame: Up to 15 years ]
- CRR is defined as the incidence of CR as best response to treatment by the Lugano Classification (Cheson et al, 2014)
- DOR [ Time Frame: Up to 15 years ]
- DOR is defined only for subjects who experience an objective response and is the time from the first objective response to disease progression per (Cheson et al, 2014) or disease-related death, whichever comes first.
- PFS [ Time Frame: Up to 15 years ]
- PFS is defined as the time from the axicabtagene ciloleucel infusion date to the date of disease progression per (Cheson et al, 2014) or death from any cause.
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events [ Time Frame: Up to 2 years ]
- Overall Survival (OS) [ Time Frame: Up to 15 years ]
- OS is defined as the time from KTE-C19 infusion to the date of death.
- Levels of anti-CD19 CAR T cells in blood [ Time Frame: At enrollment, Day 7, Week 2, Week 4, Month 3, Month 6, Month 12, Month 18, Month 24, annually up to year 5]
- Levels of cytokines in serum [ Time Frame: At enrollment, prior to axicabtagene ciloleucel infusion on Day 0, Day 3, Day 7, Week 2, Week 4 ]
- Percentage of Participants experiencing anti-axicabtagene ciloleucel antibodies [ Time Frame: At enrollment, Week 4, Month 3, every 3 months up to Month 12 ]
- Percentage of Participants Experiencing clinically significant changes in lab values [ Time Frame: Up to 5 years ]
Original Secondary Outcome Measures:
- Progression Free Survival [ Time Frame: 12 months ]
- The time from the axicabtagene ciloleucel infusion date to the date of disease progression per the revised IWG Response Criteria for Malignant Lymphoma (Cheson 2007) or death from any cause.
- Overall Survival [ Time Frame: 12 months ]
- Defined as the time from axicabtagene ciloleucel infusion to the date of death.
- Incidences of AEs [ Time Frame: 12 months ]
- The frequency of any AEs that occurred during study participation.
- Clinical significant changes in lab values. [ Time Frame: 12 months ]
- The occurrence of any changes in lab values deemed to be clinically significant during study participation.
Phase : II
Stade : NA