Fludarabine, Cyclophosphamide, and Rituximab or Alemtuzumab in Treating CLL2007 CLL 2007 FMP

July 24, 2013 updated by: French Innovative Leukemia Organisation

Randomized Phase-III Trial Comparing Fludarabine and Cyclophosphamide Plus Rituximab (FCR) to FC and MabCampath (FCCam) for Previously Untreated Fit Patients With Chronic Lymphocytic Leukemia (CLL)

RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to kill cancer cells or stop them from growing. Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some find cancer cells and help kill them or carry cancer-killing substances to them. Others interfere with the ability of cancer cells to grow and spread. It is not yet known whether giving fludarabine and cyclophosphamide together with rituximab is more effective than giving fludarabine and cyclophosphamide together with alemtuzumab in treating B-cell chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying giving fludarabine together with cyclophosphamide and rituximab to see how well it works as first-line therapy compared with giving fludarabine together with cyclophosphamide and alemtuzumab in treating patients with B-cell chronic lymphocytic leukemia.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • To compare 36-month progression-free survival in patients with Binet stage B or C B-cell chronic lymphocytic leukemia treated with first-line therapy comprising fludarabine phosphate and cyclophosphamide and either rituximab or alemtuzumab.

Secondary

  • To compare the disease-free survival, event-free survival, and overall survival of patients treated with these regimens.
  • To compare time to next treatment in patients treated with these regimens.
  • To compare the overall response rate (complete response [CR] and partial response [PR]) in patients treated with these regimens.
  • To compare the rate of phenotypic and molecular response in patients treated with these regimens.
  • To compare the duration of phenotypic, molecular, complete and partial responses in patients treated with these regimens.
  • To compare the response rates and survival times in biological subgroups.
  • To compare the rates of treatment-related adverse effects in patients treated with these regimens.
  • To compare the quality of life of patients treated with these regimens.
  • Minimal residual disease study.

OUTLINE: This is a multicenter study. Patients are stratified according to Ig mutational status and cytogenetic abnormalities. Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive rituximab IV on day 1 and fludarabine phosphate and cyclophosphamide IV or orally on days 2-4 of course 1. Beginning in course 2 and for all subsequent courses, patients receive rituximab IV on day 1 and fludarabine phosphate and cyclophosphamide IV or orally on days 1-3.
  • Arm II: Patients receive alemtuzumab subcutaneously, oral fludarabine phosphate, and oral cyclophosphamide on days 1-3.

In both arms, treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 6 months.

Study Type

Interventional

Enrollment (Actual)

178

Phase

  • Phase 3

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
      • Rouen, France, 76038
        • Centre Henri Becquerel

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

DISEASE CHARACTERISTICS:

Inclusion

Diagnosis of B-cell chronic lymphocytic leukemia (CLL), meeting the following criteria:

  • Binet classification stages B or C
  • Del 17 p (FISH) negative (< 10 % positives cores)
  • Matutes score 4 or 5

Exclusion Transformation to aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma, or prolymphocytic leukemia)

PATIENT CHARACTERISTICS:

Exclusion ECOG performance status ≥ 2

  • Life expectancy < 6 months
  • Creatinine clearance < 60 mL/min
  • Total bilirubin > 2 x upper limit of normal (ULN)
  • Gamma glutamyltransferase or transaminase levels > 2 x ULN
  • Cumulative illness rating scale > 6
  • HIV seropositivity
  • Hepatitis B or C seropositivity (unless clearly due to vaccination)
  • Clinically significant autoimmune anemia
  • Active bacterial, viral, or fungal infection
  • Active second malignancy currently requiring treatment (except basal cell carcinoma or in situ endometrial carcinoma) and/or less than 5 years complete remission after breast cancer

  • Any severe comorbid conditions including, but not limited to, any of the following:

    • Class III or IV heart failure
    • Recent myocardial infarction
    • Unstable angina
    • Ventricular tachyarrhythmias requiring ongoing treatment
    • Severe chronic obstructive pulmonary disease with hypoxemia
    • Uncontrolled diabetes mellitus
    • 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
  • Contraindication to the use of rituximab or alemtuzumab according to Summary of Product Characteristics
  • Any coexisting medical or psychological condition that would preclude participation in the required study procedures
  • Any mental deficiency preventing proper understanding of the requirements of treatment
  • Person under law control
  • Pregnant or breastfeeding women
  • Fertile 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

PRIOR CONCURRENT THERAPY:

Inclusion

  • No prior chemotherapy, radiotherapy, or immunotherapy for CLL
  • Corticosteroids within the past month allowed

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
Experimental: FCCAM
Fludarabine-Cyclophosphamide-Campath (FCCam) Oral Fludarabine: 40 mg/m2 per os, D1 to D3 Oral Cyclophosphamide: 250 mg/m2/day as one dose at noon, D1 to D3 Campath®: 30 mg sc, D1 to D3 without dose escalation
Biological: rituximab
Fludarabine-Cyclophosphamide-Rituximab (FCR)
Other Names:
  • Mabthera®
Drug: cyclophosphamide
Fludarabine-Cyclophosphamide-Campath (FCCAM) Fludarabine-Cyclophosphamide-Rituximab (FCR)
Other Names:
  • Endoxan®
Drug: fludarabine
Fludarabine-Cyclophosphamide-Campath (FCCAM) Fludarabine-Cyclophosphamide-Rituximab (FCR)
Other Names:
  • Fludara®
Active Comparator: FCR

Fludarabine-Cyclophosphamide-Rituximab (FCR)

First course:

Rituximab 375 mg/m2 on D1.

D2 to D4:

oral Fludarabine: 40 mg/m2/day as a single morning dose oral Cyclophosphamide: 250 mg/m2/day as a single dose at noon

Subsequent courses (2 to 6)

Rituximab 500 mg/m2 on D1

D1 to D3:

oral Fludarabine: 40 mg/m2/day as a single morning dose oral Cyclophosphamide: 250 mg/m2/day as a single dose at noon
Drug: cyclophosphamide
Fludarabine-Cyclophosphamide-Campath (FCCAM) Fludarabine-Cyclophosphamide-Rituximab (FCR)
Other Names:
  • Endoxan®
Biological: Campath
Fludarabine-Cyclophosphamide-Campath (FCCam)
Other Names:
  • Alemtuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Progression-free survival at 36 months
Time Frame: 36 months follow up
36 months follow up

Secondary Outcome Measures

Outcome Measure
Time Frame
Disease-free survival
Time Frame: 36 months follow up
36 months follow up
Event-free survival
Time Frame: 36 months follow up
36 months follow up
Overall survival
Time Frame: 36 months follow up
36 months follow up
Time to next treatment
Time Frame: 36 months follow up
36 months follow up
Overall response rate (complete response [CR] and partial response [PR])
Time Frame: 36 months follow up
36 months follow up
Duration of phenotypic, molecular, NCI complete and partial responses
Time Frame: 36 months follow up
36 months follow up
Response rates and survival times in biological subgroups
Time Frame: 36 months follow up
36 months follow up
Treatment-related adverse effects
Time Frame: 36 months follow up
36 months follow up

Collaborators and Investigators

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

Sponsor

French Innovative Leukemia Organisation

Investigators

  • Study Chair: Stephane Lepretre, MD, Centre Henri Becquerel
  • Principal Investigator: Pierre Feugier, CHU de Nancy - Hôpitaux de Brabois
  • Study Director: Roselyne DELEPINE, mrs, Groupe Est Ouest Etudes leucemies et Autres Maladies du Sang

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

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

November 1, 2007

Primary Completion (Actual)

January 1, 2009

Study Completion (Actual)

July 1, 2013

Study Registration Dates

First Submitted

November 27, 2007

First Submitted That Met QC Criteria

November 27, 2007

First Posted (Estimate)

November 28, 2007

Study Record Updates

Last Update Posted (Estimate)

July 25, 2013

Last Update Submitted That Met QC Criteria

July 24, 2013

Last Verified

April 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000577580
  • CLL-2007-FMP (Other Identifier: GOELAMS)

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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