Intensified Rituimab Prephase Before FCR in Untreated B-CLL

March 15, 2016 updated by: French Innovative Leukemia Organisation

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

140

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • CLCC Henri Becquerel
      • Rouen, CLCC Henri Becquerel, France, 76038
        • Stephane LEPRETRE
    • Regional university Hospital
      • Montpellier, Regional university Hospital, France, 34295
        • Guillaume CARTRON

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard R-FC arm

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
Drug: Rituximab
  • Cycle 1 Rituximab : 375 mg/m² i.v on day 1
  • Cycle 2-6 Rituximab:500 mg/m² i.v on day 1, repeated every 28 days
Other Names:
  • R
Drug: Rituximab
  • Prephase: Rituximab:500 mg on day 0, 2000 mg on days 1, 8, and D15
  • Cycle 1-6 cycle 1 beginning at D22: Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days
Other Names:
  • R
Drug: Cyclophosphamide
•FCR Cycle 1-6: Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
Other Names:
  • C
Drug: Fludarabine
FCR Cycle 1-6: Fludarabine :40 mg/m² per os, days 2-4, repeated every 28 days
Other Names:
  • F
Experimental: DenseR-FC arm

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
Drug: Rituximab
  • Cycle 1 Rituximab : 375 mg/m² i.v on day 1
  • Cycle 2-6 Rituximab:500 mg/m² i.v on day 1, repeated every 28 days
Other Names:
  • R
Drug: Rituximab
  • Prephase: Rituximab:500 mg on day 0, 2000 mg on days 1, 8, and D15
  • Cycle 1-6 cycle 1 beginning at D22: Rituximab: 500 mg/m2 i.v on day 1, repeated every 28 days
Other Names:
  • R
Drug: Cyclophosphamide
•FCR Cycle 1-6: Cyclophosphamide : 250 mg/m² per os, days 2-4, repeated every 28 days
Other Names:
  • C
Drug: Fludarabine
FCR Cycle 1-6: Fludarabine :40 mg/m² per os, days 2-4, repeated every 28 days
Other Names:
  • F

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

French Innovative Leukemia Organisation

Collaborators

Roche Pharma AG

Investigators

  • Principal Investigator: Guillaume CARTRON, MD PD, French Innovative Leukemia Organisation
  • Principal Investigator: Stephane LEPRETRE, MD, French Innovative Leukemia Organisation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2011

Primary Completion (Actual)

September 1, 2014

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

May 23, 2011

First Submitted That Met QC Criteria

June 9, 2011

First Posted (Estimate)

June 10, 2011

Study Record Updates

Last Update Posted (Estimate)

March 16, 2016

Last Update Submitted That Met QC Criteria

March 15, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CLL 2010 FMP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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