Intensified Rituimab Prephase Before FCR in Untreated B-CLL

Phase 2

Completed

• Conditions: B-cell Chronic Lymphocytic Leukemia CLL
• Interventions: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Fludarabine

• Registration Number: NCT01370772
• Lead Sponsor: French Innovative Leukemia Organisation

Brief Summary

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

Detailed 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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2011-05
• Study First Submitted: 2011-05-23
• Study First Submitted QC: 2011-06-09
• Study First Posted: 2011-06-10
• Primary Completion: 2014-09
• Status Verified: 2016-03
• Study Completion: 2016-03
• Last Update Submitted: 2016-03-15
• Last Update Posted: 2016-03-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 140

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DenseR-FC arm	Cyclophosphamide	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
Standard R-FC arm	Fludarabine	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
Standard R-FC arm	Rituximab	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
DenseR-FC arm	Rituximab	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
Standard R-FC arm	Cyclophosphamide	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
DenseR-FC arm	Fludarabine	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

Primary Outcome Measures

Name	Time	Method
complete response rates according to IWCLL 2008 guidelines with undetectable minimal residual disease	9 months	CR MRD negative rate at 9 months = treatment evaluation surveillance of cumulative toxicities of high dose rituximab

Secondary Outcome Measures

Name	Time	Method
evaluate the immunophenotypic response rate after high dose Rituximab alone prephase in DenseR-FC	9 months	Treatment evaluation
To determine the pharmacokinetics of rituximab and determine the PK-PD relationship of rituximab based on biomarkers.	12 months
To determine and compare the progression free survival PFS	3 years
To determine the event-free survival EFS	3 years
To evaluate the safety profile of higher doses of rituximab	41	5 months treatment and 36 months follow up
To evaluate FcyRs polymorphisms influence on clinical response	9 months	R Dense arm treatment evaluation
To determine the overall survival OS	3 years
To determine and compare the disease-free survival DFS	3 years
To determine the time to next treatment TTNT	3 years

Trial Locations

Locations (2)

Stephane LEPRETRE; 🇫🇷 Rouen, CLCC Henri Becquerel, France

Guillaume CARTRON; 🇫🇷 Montpellier, Regional university Hospital, France