B-cell Chronic Lymphocytic Leukemia CLL Clinical Trial
Official title:
Phase II Multicentric, Randomized Trial, Exploring Intensified Rituximab Prephase Monotherapy Before Standard Fludarabine-Cyclophosphamide-Rituximab Regimen in Previously Untreated Symptomatic B-cell Chronic Lymphocytic Leukemia
Phase II, multicenter, randomized trial, exploring intensified Rituximab prephase
monotherapy before standard Fludarabine-Cyclophosphamide-Rituximab FC-R regimen in
previously untreated symptomatic B-cell chronic lymphocytic leukemia CLL.
A Study from the Goelams GCFLLCMW intergroup
| Status | Completed |
| Enrollment | 140 |
| Est. completion date | March 2016 |
| Est. primary completion date | September 2014 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 65 Years |
| Eligibility |
Inclusion criteria: - Patient information and written informed consent - 18 years < Age < 66 ans - confirmed B-CLL Matutes score 4 or 5 - Binet stage C or Binet stage A and B with active disease could be considered for inclusion. For stage A with active disease an agreement of investigator coordinator is required. - no prior treatment except steroids for less than 1 month (detail corticoid) - No 17p deletion as assessed by FISH < 10 % positive nuclei - Performance status ECOG < 2 - CIRS Cumulative Illness Rating Scale < 6 Exclusion criteria: - Binet stage A without active disease according to IWCLL 2008 criteria - Know HIV seropositivity - Hepatitis B or C seropositivity unless clearly due to vaccination - Life expectancy < 6 months - Clinically significant auto-immune anemia - Active second malignancy currently requiring treatment (except basal cell carcinoma in situ endometrial carcinoma and incidental prostate carcinoma) and/or less than 5 years CR after breast cancer - Any severe co-morbid conditions such as Class III or IV heart failure, myocardial infarction within 6 months, unstable angina, ventricular tachyarythmias requiring ongoing treatment, severe chronic obstructive pulmonary disease with hypoxemia, uncontrolled diabetes mellitus, or uncontrolled hypertension - Concomitant disease requiring prolonged use of corticosteroids > 1 month - Known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs According to the SmPC or investigator practice - Contraindication to use of Rituximab - Transformation to aggressive B-cell malignancy e.g. diffuse large cell lymphoma, Hodgkin lymphoma, or prolymphocytic leukaemia - Active bacterial, viral or fungal infection - Abnormal renal function with creatinine clearance < 60 ml/min calculated according to the Cockcroft and Gault formula - Total bilirubin, gamma glutamyltransferase or transaminase levels > 2.5 ULN. - Any coexisting medical or psychological condition that would preclude participation in the required study procedures - Patient with mental deficiency preventing proper understanding of the requirements of treatment. - Pregnant or breastfeeding women. - Adult under law-control - Fertile male and female patients who cannot or do not wish to use an effective method of contraception, during and for 12 months after the final treatment used for the purposes of the study. - No afiliate to social security |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| France | Guillaume CARTRON | Montpellier | Regional university Hospital |
| France | Stephane LEPRETRE | Rouen | CLCC Henri Becquerel |
| Lead Sponsor | Collaborator |
|---|---|
| French Innovative Leukemia Organisation | Roche Pharma AG |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease | CR MRD negative rate at 9 months = treatment evaluation surveillance of cumulative toxicities of high dose rituximab | 9 months | Yes |
| Secondary | To determine and compare the progression free survival PFS | 3 years | Yes | |
| Secondary | evaluate the immunophenotypic response rate after high dose Rituximab alone prephase in DenseR-FC | Treatment evaluation | 9 months | Yes |
| Secondary | To evaluate FcyRs polymorphisms influence on clinical response | R Dense arm treatment evaluation | 9 months | Yes |
| Secondary | To determine the pharmacokinetics of rituximab and determine the PK-PD relationship of rituximab based on biomarkers. | 12 months | Yes | |
| Secondary | To evaluate the safety profile of higher doses of rituximab | 5 months treatment and 36 months follow up | 41 | Yes |
| Secondary | To determine the event-free survival EFS | 3 years | Yes | |
| Secondary | To determine and compare the disease-free survival DFS | 3 years | Yes | |
| Secondary | To determine the overall survival OS | 3 years | Yes | |
| Secondary | To determine the time to next treatment TTNT | 3 years | Yes |