RATIONALE: Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others can find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving fludarabine together with rituximab followed by alemtuzumab may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving fludarabine together with rituximab followed by alemtuzumab works in treating patients with chronic lymphocytic leukemia.

Condition	Treatment or Intervention	Phase
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	Drug: alemtuzumab  Drug: fludarabine  Drug: rituximab  Procedure: antibody therapy  Procedure: biological response modifier therapy  Procedure: chemotherapy  Procedure: monoclonal antibody therapy	Phase II

Further Study Details: 

OBJECTIVES: Primary

• Determine the rate of complete response in patients with previously untreated B-cell chronic lymphocytic leukemia (CLL) treated with induction therapy comprising fludarabine and rituximab followed by consolidation therapy comprising alemtuzumab.
• Determine the toxicity of this regimen in these patients.
• Determine whether alemtuzumab improves the complete response rate with acceptable toxicity in patients treated with this regimen.
• Determine the progression-free and overall survival of high-risk and low-risk patients treated with this regimen.
• Determine the frequency of molecular remission in patients treated with this regimen.

Secondary

• Determine the clinical and molecular features that predict poor response to this regimen in these patients.
• Determine the frequency of patients who remain at high risk for progression of CLL despite treatment with this regimen.
• Determine the pharmacokinetics and ideal schedule of administration for a subsequent maintenance therapy approach with rituximab in these patients.

OUTLINE: This is a multicenter study.

Patients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5 of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.

Approximately 4 months after completion of induction therapy, patients achieving a complete response, partial response, or stable disease receive consolidation therapy comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6 courses in the absence of disease progression.

Patients are followed at 2 months, every 3 months for 1 year, and then every 6 months for 7 years from study entry.

PROJECTED ACCRUAL: A total of 100 patients will be accrued for this study within 2 years.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL)
• Absolute lymphocyte count > 5,000/mm
• Lymphocytes must appear mature with < 55% prolymphocytes
• Bone marrow aspirate smear with > 30% of all nucleated cells shown to be lymphoid OR bone marrow core biopsy showing lymphoid infiltrates compatible with marrow involvement by CLL
• Overall cellularity must be normocellular or hypercellular
• Lymphocyte phenotype revealing predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, or CD23) with the CD5 antigen in the absence of other pan-T-cell markers
• B-cells must be monoclonal with regard to expression of either kappa or lambda and have surface immunoglobulin expression of low density
• Patients with bright surface immunoglobulin levels must have CD23 coexpression
• Intermediate- or high-risk disease
• Stage I, II, III, or IV disease
• Patients with intermediate-risk disease must have evidence of active disease as evidenced by meeting at least 1 of the following criteria:
• Massive or progressive splenomegaly, hepatomegaly, and/or lymphadenopathy
• Weight loss > 10% within the past 6 months
• Grade 2 or 3 fatigue
• Fevers > 100.5°F or night sweats for more than 2 weeks without evidence of infection
• Progressive lymphocytosis with an increase of > 50% over 2 months OR an anticipated doubling time of < 6 months
• High-risk disease defined as 1 of the following:
• Hemoglobin < 11 g/dL
• Platelet count < 100,000/mm^3

PATIENT CHARACTERISTICS: Age

• 18 and over

Performance status

• 0-2

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• See Disease Characteristics

Renal

• Creatinine ≤ 1.5 times upper limit of normal

Other

• Not pregnant
• No nursing during and for ≥ 3 months after study participation
• Fertile patients must use effective contraception during and for ≥ 6 months after study participation
• HIV negative
• Coombs’ test negative

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• No other concurrent chemotherapy

Endocrine therapy

• No prior corticosteroids for autoimmune complications that have developed since initial diagnosis of CLL
• No concurrent hormonal therapy except for the following:
• Hypersensitivity reactions
• Steroids for new adrenal failure
• Hormones administered for non-disease-related conditions (e.g., insulin for diabetes)
• No concurrent chronic oral corticosteroids
• No concurrent dexamethasone or other corticosteroids as antiemetic prophylaxis

Radiotherapy

• No concurrent palliative radiotherapy

Surgery

• Not specified

Other

• No prior therapy for CLL

Ohio
      Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University, Columbus,  Ohio,  43210-1240,  United States; Recruiting

Study chairs or principal investigators

John C. Byrd, MD,  Study Chair,  Arthur G. James Cancer Hospital & Richard J. Solove Research Institute   
Kanti Roop Rai, MD,  Long Island Jewish Medical Center   

Study ID Numbers:  CDR0000398139; CALGB-10101; NCT00098670
Record last reviewed:  November 2004
Last Updated:  February 4, 2005
Record first received:  December 7, 2004
ClinicalTrials.gov Identifier:  NCT00098670
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08