Fludarabine with or without Cyclophosphamide for Untreated Chronic Lymphocytic Leukemia
cyclophosphamide
+ fludarabine phosphate
Chronic Disease+13
+ Hematologic Diseases
+ Hemic and Lymphatic Diseases
Treatment Study
Summary
Study start date: March 9, 2000
Actual date on which the first participant was enrolled.OBJECTIVES: Compare the efficacy of fludarabine with or without cyclophosphamide in terms of complete remission rate and overall survival in patients with previously untreated B cell chronic lymphocytic leukemia (CLL). Compare the toxicities of these 2 regimens in this patient population. Determine whether the expression of proteins specifically implicated in the regulation of DNA damage induced apoptosis of lymphoid cells (i.e., p53; mdm2; GST; Bcl-2; Mcl-1; Bax; p27; and caspase-3) correlates with response to chemotherapy in these patients. Determine whether there is a relationship between clinical response or resistance and differential expression of genes in the CLL cells either at initiation of therapy or following relapse and progression. Correlate mutations in immunoglobulin heavy chain variable region genes with clinical response or resistance in this patient population. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to stage of disease (O-II vs III-IV). Patients are randomized to one of two treatment arms. Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5. Arm II: Patients receive fludarabine as in arm I plus cyclophosphamide IV over 1 hour on day 1. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 3 months for 2 years and then every 6 months until disease progression. PROJECTED ACCRUAL: A total of 280 patients will be accrued for this study over 2 to 2.5 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.280 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 120 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: Diagnosis of chronic lymphocytic leukemia (CLL) of any stage as defined by the following: Peripheral blood absolute lymphocyte count greater than 5,000/mm^3 within 14 days prior to study Lymphocytes must be small to moderate size with no more than 55% prolymphocytes, atypical lymphocytes, or lymphoblasts morphologically Phenotypically characterized as B-CLL Must have one of the following characteristics indicating need for chemotherapy: Progressive marrow failure (hemoglobin less than 10 g/dL and/or platelet count less than 100,000/mm^3) Progressive lymphocytosis with an increase of more than 50% over a 2 month period or anticipated doubling time of less than 6 months Massive (i.e., greater than 6 cm below left costal margin) or progressive splenomegaly Massive nodes or clusters (i.e., greater than 10 cm in longest diameter) or progressive adenopathy At least 10% weight loss within 6 months of study Extreme fatigue Fevers greater than 100.5 degrees F for 2 weeks without evidence of infection Night sweats without evidence of infection No autoimmune anemia or autoimmune thrombocytopenia PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 2 mg/dL unless secondary to tumor Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 40 mL/min if creatinine is greater than 1.5 mg/dL Other: No other prior or concurrent malignancy within the past 2 years except basal cell carcinoma of the skin or carcinoma in situ of the cervix No active infection requiring oral or intravenous antibiotics Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No prior cytotoxic chemotherapy Endocrine therapy: No prior steroid treatment for CLL Radiotherapy: Not specified Surgery: Not specified
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 218 locations
Northeast Alabama Regional Medical Center
Anniston, United StatesOpen Northeast Alabama Regional Medical Center in Google MapsUniversity of Alabama at Birmingham Comprehensive Cancer Center
Birmingham, United StatesMBCCOP - Gulf Coast
Mobile, United StatesCCOP - Western Regional, Arizona
Phoenix, United States