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
  Purpose

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.


Condition Intervention Phase
Leukemia
Biological: Campath
Biological: rituximab
Drug: cyclophosphamide
Drug: fludarabine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS:

Primary Outcome Measures:
  • Progression-free survival at 36 months [ Time Frame: 36 months follow up ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 178
Study Start Date: November 2007
Study Completion Date: July 2013
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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®
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

Biological: Campath
Fludarabine-Cyclophosphamide-Campath (FCCam)
Other Name: Alemtuzumab
Drug: cyclophosphamide
Fludarabine-Cyclophosphamide-Campath (FCCAM) Fludarabine-Cyclophosphamide-Rituximab (FCR)
Other Name: Endoxan®

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00564512

Locations
France
Centre Henri Becquerel
Rouen, France, 76038
Sponsors and Collaborators
Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
Investigators
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
  More Information

Additional Information:
No publications provided by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS
ClinicalTrials.gov Identifier: NCT00564512     History of Changes
Other Study ID Numbers: CDR0000577580, CLL-2007-FMP
Study First Received: November 27, 2007
Last Updated: July 24, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang GOELAMS:
B-cell chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia
stage II chronic lymphocytic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Alemtuzumab
Cyclophosphamide
Fludarabine
Fludarabine phosphate
Rituximab
Vidarabine
Alkylating Agents
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014