ASCT After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma

Summary

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Description

Objectives and Endpoints Primary Objective: To establish one of three study arms, R-CHOP/R-DHAP followed by ASCT (control arm A), R-CHOP+ibrutinib /R-DHAP followed by ASCT and ibrutinib maintenance experimental arm A+I), and R-CHOP+ibrutinib /R-DHAP followed by ibrutinib maintenance experimental arm...

Objectives and Endpoints Primary Objective: To establish one of three study arms, R-CHOP/R-DHAP followed by ASCT (control arm A), R-CHOP+ibrutinib /R-DHAP followed by ASCT and ibrutinib maintenance experimental arm A+I), and R-CHOP+ibrutinib /R-DHAP followed by ibrutinib maintenance experimental arm I) as future standard based on the comparison of the investigator-assessed failure-free survival (FFS). Secondary Objectives: To compare the efficacy of the three treatment arms in terms of secondary efficacy endpoints To determine the safety and tolerability of ibrutinib during induction immuno-chemotherapy and during maintenance and to compare the safety profile of the three treatment arms in terms of secondary toxicity endpoints Primary Endpoint: FFS defined as time from start of treatment to stable disease at end of immuno-chemotherapy, progressive disease, or death from any cause. Secondary Efficacy Endpoints: Overall survival (OS) Progression-free survival (PFS) from randomization, from end of induction immuno-chemotherapy in patients with CR or PR at end of induction immuno-chemotherapy, and from the staging 6 weeks after end of induction assessment (at month 6) Overall response and complete remission rates at midterm, at end of induction, 3 months after end of induction immunochemotherapy (at month 6) PR to CR conversion rate during follow-up after end of induction immuno-chemotherapy Secondary Toxicity Endpoints: Rates of AEs, SAEs, and SUSARs by CTC grade (Version 4.03) during induction immuno-chemotherapy and during periods of follow-up after response to immune-chemotherapy Cumulative incidence rates of SPMs Exploratory Objectives: To compare feasibility of ASCT in arm A+I vs. arm A To compare minimal residual disease status between the three treatment groups To determine the impact of ibrutinib during induction immuno-chemotherapy and during maintenance therapy on the minimal residual disease status To determine the prognostic value of minimal residual disease status To determine the prognostic value of positron emission tomography with fluorine 18-fluorodeoxyglucose To determine clinical and biological prognostic and predictive factors To determine the role of total body irradiation (TBI) in ASCT conditioning Exploratory Endpoints: Rate of successful stem cell mobilisations (success: separation of at least 2x2x10(6) CD34-positive cells, including a back-up) Rate of molecular remissions (MRD-negative patients) at midterm, at end of induction immuno-chemotherapy, and at staging time-points during follow-up in patients with remission after end of induction immuno-chemotherapy Time to molecular remission from start of therapy Time to molecular relapse for patients in clinical and molecular remission after end of induction immunochemotherapy RD in FDG-PET negative or positive patients after induction and ASCT Exploratory objectives may be evaluated only in a subset of patients according to local standards and resources.

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