Ignite Creation Date:
2025-12-26 @ 2:38 PM
Ignite Modification Date:
2026-03-03 @ 2:20 PM
Study NCT ID:
NCT00645606
Status:
COMPLETED
Last Update Posted:
2017-08-01
First Post:
2008-03-26
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Rituximab Maintenance Versus Observation After First-line Immunochemotherapy by FCR in Older Patients With Chronic Lymphocytic Leukemia
Sponsor:
University Hospital, Tours
Organization:
Study Overview
Official Title:
Single-agent Rituximab as Maintenance Treatment Versus Observation After Combined Induction Immunochemotherapy With Fludarabine, Cyclophosphamide and Rituximab in Patients Older Than 65 Years With Previously Untreated Chronic Lymphocytic Leukemia: a Phase III Trial of FILO
Status:
COMPLETED
Status Verified Date:
2017-07
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:
LLC2007SA
Brief Summary:
RATIONALE: Classical chemotherapy does not cure advanced chronic lymphocytic leukemia (CLL) despite new drugs. Rituximab is a monoclonal antibody directed against CD20 surface antigen on B lymphocytes and leads to apoptosis of CD20 positive B lymphocytes. The highest response rate yet published in the treatment of first-line CLL has been obtained by the association of fludarabine, cyclophosphamide and rituximab (FCR). Now, the question is whether this response can be improved, as some trials showed that eradication of minimal residual disease (MRD) in CLL is associated with a longer treatment-free and overall survival. Maintenance therapy using rituximab has been recently approved as a means of prolonging remission in patients with indolent non Hodgkin's lymphoma. Maintenance therapy with rituximab could be of interest in treatment of MRD in CLL and prolonging remission and survival times.
PURPOSE: The overall purpose of the study is to determine the value of immunotherapy maintenance with single agent rituximab in comparison with no further treatment (observation ) for previously untreated chronic lymphocytic leukaemia in elderly (\>65 years) patients who respond to induction immunochemotherapy with FCR.
PURPOSE: The overall purpose of the study is to determine the value of immunotherapy maintenance with single agent rituximab in comparison with no further treatment (observation ) for previously untreated chronic lymphocytic leukaemia in elderly (\>65 years) patients who respond to induction immunochemotherapy with FCR.
Detailed Description:
OBJECTIVES:
Primary
* To demonstrate superiority, in terms of 3-year progression-free survival (PFS), of rituximab maintenance over observation in patients who are in complete or partial response (CR or PR) after induction therapy comprising fludarabine, cyclophosphamide, and rituximab.
Secondary
* To determine event-free survival, disease-free survival, overall survival, and time to next treatment, all from time of randomization.
* To determine overall response rate (CR and PR) according to NCI and iwCLL criteria
* To assess the rate of phenotypic response (minimal residual disease).
* To assess duration of phenotypic and NCI and iwCLL clinical responses.
* To determine response rates and time-related parameters in biological subgroups.
* To determine rates of treatment-related adverse events.
* To evaluate CD4/CD8 counts, immunoglobulin levels, and incidence of Coombs-positive hemolytic anemia.
* To study pharmacokinetics of rituximab during induction and maintenance.
* To evaluate the prognostic impact of the immunoglobulin FcγRIIIA genotype.
* To assess quality of life.
* To study pharmacoeconomics.
OUTLINE: This is a multicenter study. Randomization is stratified according to response to induction therapy (complete response \[CR\] vs partial response \[PR\]), IGHV mutational status, and 11q deletion.
Patients receive rituximab IV on days 1 and 14 of courses 1-2 and on day 1 of courses 3 and 4. Patients also receive oral fludarabine and oral cyclophosphamide once daily on days 2-4 of course 1 and on days 1-3 of courses 2-4. Courses are administered every 28 days. Patients achieving CR or PR are randomized 1:1 to maintenance arm or observation arm.
* Arm A: Patients receive rituximab IV every 2 months in the absence of disease progression or unacceptable toxicity for a maximum duration of 24 months (12 infusions).
* Arm B: Patients undergo observation only.
After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for 2 years.
Primary
* To demonstrate superiority, in terms of 3-year progression-free survival (PFS), of rituximab maintenance over observation in patients who are in complete or partial response (CR or PR) after induction therapy comprising fludarabine, cyclophosphamide, and rituximab.
Secondary
* To determine event-free survival, disease-free survival, overall survival, and time to next treatment, all from time of randomization.
* To determine overall response rate (CR and PR) according to NCI and iwCLL criteria
* To assess the rate of phenotypic response (minimal residual disease).
* To assess duration of phenotypic and NCI and iwCLL clinical responses.
* To determine response rates and time-related parameters in biological subgroups.
* To determine rates of treatment-related adverse events.
* To evaluate CD4/CD8 counts, immunoglobulin levels, and incidence of Coombs-positive hemolytic anemia.
* To study pharmacokinetics of rituximab during induction and maintenance.
* To evaluate the prognostic impact of the immunoglobulin FcγRIIIA genotype.
* To assess quality of life.
* To study pharmacoeconomics.
OUTLINE: This is a multicenter study. Randomization is stratified according to response to induction therapy (complete response \[CR\] vs partial response \[PR\]), IGHV mutational status, and 11q deletion.
Patients receive rituximab IV on days 1 and 14 of courses 1-2 and on day 1 of courses 3 and 4. Patients also receive oral fludarabine and oral cyclophosphamide once daily on days 2-4 of course 1 and on days 1-3 of courses 2-4. Courses are administered every 28 days. Patients achieving CR or PR are randomized 1:1 to maintenance arm or observation arm.
* Arm A: Patients receive rituximab IV every 2 months in the absence of disease progression or unacceptable toxicity for a maximum duration of 24 months (12 infusions).
* Arm B: Patients undergo observation only.
After completion of study therapy, patients are followed every 3 months for 1 year and then every 6 months for 2 years.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: