Intensified Rituimab Prephase Before FCR in Untreated B-CLL

French Innovative Leukemia Organisation

Status and phase: Completed; Phase 2

Conditions: B-cell Chronic Lymphocytic Leukemia CLL

Treatments: Drug: Fludarabine; Drug: Rituximab; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01370772

CLL 2010 FMP

Details and patient eligibility

About

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

Full description

Young fit medically B Cell untreated patients Comparison between FCR treatment = 6 FCR cycles and a the addition of a prephase with R Dense treatment before the 6 FCR cycles.

Enrollment: 140 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

140 participants in 2 patient groups

Standard R-FC arm

Active Comparator group

Description:

Standard R-FC arm 6 cycles every 28 days * Cycle 1: * Rituximab : 375 mg/m² i.v on day 1 * Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days * Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days For patients with Leucocyte count \> 25\* G/L : rituximab in two equal doses at D1, D2 * Cycle 2-6: * Rituximab: 500 mg/m² i.v on day 1, repeated every 28 days * Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days * Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days

Treatment:

Drug: Cyclophosphamide

Drug: Rituximab

Drug: Fludarabine

Drug: Rituximab

DenseR-FC arm

Experimental group

Description:

DenseR-FC arm =1 prephase R Dense course +6 R-FC courses * Prephase: - Rituximab: 500 mg on day 0, 2000 mg on days 1, 8, and D15 For patients with Leucocyte count \> 25\* G/L : rituximab 250 mg D-1, D0 prephase * Cycle 1-6 (cycle 1 beginning at D22): * Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days * Fludarabine : 40 mg/m² per os, days 2-4, repeated every 28 days * Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days

Treatment:

Drug: Cyclophosphamide

Drug: Rituximab

Drug: Fludarabine

Drug: Rituximab