Ignite Creation Date:
2025-12-25 @ 12:14 AM
Ignite Modification Date:
2026-01-04 @ 4:54 PM
Study NCT ID:
NCT02858258
Status:
RECRUITING
Last Update Posted:
2017-12-19
First Post:
2016-07-14
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
ASCT After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma
Sponsor:
Prof. Dr. M. Dreyling (co-chairman)
Organization:
Study Overview
Official Title:
Autologous Transplantation After a Rituximab/Ibrutinib/Ara-c Containing iNduction in Generalized Mantle Cell Lymphoma - a Randomized European Mcl Network Trial
Status:
RECRUITING
Status Verified Date:
2017-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The primary objective of the the trial is to establish one of three study arms, as future standard based on the comparison of the investigator-assessed failure-free survival.
Detailed 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 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.
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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: