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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
ClinicalTrials.gov Identifier:
NCT00564512
First received: November 27, 2007
Last updated: July 24, 2013
Last verified: April 2009

November 27, 2007
July 24, 2013
November 2007
January 2009   (final data collection date for primary outcome measure)
Progression-free survival at 36 months [ Time Frame: 36 months follow up ] [ Designated as safety issue: No ]
Progression-free survival at 36 months
Complete list of historical versions of study NCT00564512 on ClinicalTrials.gov Archive Site
  • Disease-free survival [ Time Frame: 36 months follow up ] [ Designated as safety issue: No ]
  • Event-free survival [ Time Frame: 36 months follow up ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 36 months follow up ] [ Designated as safety issue: No ]
  • Time to next treatment [ Time Frame: 36 months follow up ] [ Designated as safety issue: No ]
  • Overall response rate (complete response [CR] and partial response [PR]) [ Time Frame: 36 months follow up ] [ Designated as safety issue: No ]
  • Duration of phenotypic, molecular, NCI complete and partial responses [ Time Frame: 36 months follow up ] [ Designated as safety issue: No ]
  • Response rates and survival times in biological subgroups [ Time Frame: 36 months follow up ] [ Designated as safety issue: No ]
  • Treatment-related adverse effects [ Time Frame: 36 months follow up ] [ Designated as safety issue: Yes ]
  • Disease-free survival
  • Event-free survival
  • Overall survival
  • Time to next treatment
  • Overall-response rate (complete response [CR] and partial response [PR])
  • Duration of phenotypic, molecular, NCI complete and partial responses
  • Response rates and survival times in biological subgroups
  • Treatment-related adverse effects
  • Quality of life
Not Provided
Not Provided
 
Fludarabine, Cyclophosphamide, and Rituximab or Alemtuzumab in Treating CLL2007 CLL 2007 FMP
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • Biological: Campath
    Fludarabine-Cyclophosphamide-Campath (FCCam)
    Other Name: Alemtuzumab
  • Biological: rituximab
    Fludarabine-Cyclophosphamide-Rituximab (FCR)
    Other Name: Mabthera®
  • Drug: cyclophosphamide
    Fludarabine-Cyclophosphamide-Campath (FCCAM) Fludarabine-Cyclophosphamide-Rituximab (FCR)
    Other Name: Endoxan®
  • Drug: fludarabine
    Fludarabine-Cyclophosphamide-Campath (FCCAM) Fludarabine-Cyclophosphamide-Rituximab (FCR)
    Other Name: Fludara®
  • 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
    Interventions:
    • Biological: rituximab
    • Drug: cyclophosphamide
    • Drug: fludarabine
  • 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

    Interventions:
    • Biological: Campath
    • Drug: cyclophosphamide
Lepretre S, Aurran T, Mahé B, Cazin B, Tournilhac O, Maisonneuve H, Casasnovas O, Delmer A, Leblond V, Royer B, Corront B, Chevret S, Delépine R, Vaudaux S, Van Den Neste E, Béné MC, Letestu R, Cymbalista F, Feugier P. Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial. Blood. 2012 May 31;119(22):5104-10. doi: 10.1182/blood-2011-07-365437. Epub 2012 Feb 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
178
July 2013
January 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00564512
CDR0000577580, CLL-2007-FMP
Yes
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Not Provided
Study Chair: Stephane Lepretre, MD Centre Henri Becquerel
Principal Investigator: Pierre Feugier CHU de Nancy - Hopitaux de Brabois
Study Director: Roselyne DELEPINE, mrs Groupe Est Ouest Etudes leucemies et Autres Maladies du Sang
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
April 2009

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP