Phase III, Multicenter, European, Randomized Trial Comparing the Combination Fludarabine Phosphate-Cyclophosphamide-Rituximab (FCR) With the Combination Fludarabine Phosphate-Cyclophosphamide-Campath (FCCam) in Previously Untreated Adults With B and C Binet Stage B-chronic Lymphoid Leukemia (B-CLL)
18 Years
N/A
Both
Leukemia
Trial Information
Phase III, Multicenter, European, Randomized Trial Comparing the Combination Fludarabine Phosphate-Cyclophosphamide-Rituximab (FCR) With the Combination Fludarabine Phosphate-Cyclophosphamide-Campath (FCCam) in Previously Untreated Adults With B and C Binet Stage B-chronic Lymphoid Leukemia (B-CLL)
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression-free survival at 36 months
Safety Issue:
No
Principal Investigator
Stephane Lepretre, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Centre Henri Becquerel
Authority:
United States: Federal Government
Study ID:
CDR0000577580
NCT ID:
NCT00564512
Start Date:
November 2007
Completion Date:
Related Keywords:
- Leukemia
- 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
- Leukemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Lymphoid
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