Chronic Lymphocytic Leukemia Clinical Trial
Fludarabine Combined With Either Alemtuzumab or Rituximab in Treating Patients With Refractory or Relapsed B-Cell Chronic Lymphocytic Leukemia
Summary
RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Monoclonal antibodies, such as alemtuzumab and rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Combining chemotherapy with monoclonal antibody therapy may kill more cancer cells. It is not yet known whether fludarabine is more effective when combined with alemtuzumab or with rituximab in treating leukemia-cll/" >chronic lymphocytic leukemia.
PURPOSE: Randomized phase II trial to compare the effectiveness of combining fludarabine with either alemtuzumab or rituximab in treating patients who have refractory or relapsed B-cell chronic lymphocytic leukemia.
Full Description
OBJECTIVES:
Primary
Compare the complete response rate in patients with refractory or relapsed B-cell chronic lymphocytic leukemia treated with fludarabine and alemtuzumab vs fludarabine and rituximab.
Secondary
Compare the overall response rate in patients treated with these regimens.
Compare 1-year survival of patients treated with these regimens.
Compare time to progression in patients treated with these regimens.
Compare duration of response in patients treated with these regimens.
Compare the adverse event profile of these regimens in these patients.
Compare the molecular response rate in patients treated with these regimens.
Compare lymphocyte and lymphocyte subset recovery (CD3, CD3/CD4, CD3/CD8, CD20) in patients treated with these regimens.
Compare the time to complete response in patients treated with these regimens.
Compare the rate of cytomegalovirus reactivation and time to reactivation in patients treated with these regimens.
OUTLINE: This is a randomized, open-label, multicenter study. Patients are stratified according to prior treatment with fludarabine (yes vs no). Patients are randomized to 1 of 2 treatment arms.
Arm I: Patients receive fludarabine IV over 30 minutes on days 1-5. At least 30 minutes before fludarabine administration, patients receive alemtuzumab subcutaneously (SC) on days 1-5.
Arm II: Patients receive fludarabine as in arm I. At least 30 minutes before fludarabine administration, patients receive rituximab IV on days 1 and 4 of course 1 and on day 1 only in subsequent courses.
In both arms, treatment repeats every 28 days for 4-6 courses in the absence of disease progression or unacceptable toxicity. An interim assessment is performed during course 4. Patients achieving a partial response or stable disease receive 2 additional courses of therapy (for a total of 6 courses). Patients achieving a complete response (CR) do not receive further treatment beyond CR.
Patients are followed weekly for 2 months, monthly for 6 months, every 2 months for 6 months, and then every 6 months for 1 year.
PROJECTED ACCRUAL: A total of 150 patients (75 per treatment arm) will be accrued for this study.
Eligibility Criteria
DISEASE CHARACTERISTICS:
Diagnosis of B-cell chronic lymphocytic leukemia (CLL), defined as:
Peripheral lymphocyte count > 5,000/mm^3
Clonal CD5-, CD19-, and CD23-positive lymphocytes
Refractory to OR relapsed after prior first-line therapy
No CNS involvement with CLL
PATIENT CHARACTERISTICS:
Age
18 and over
Performance status
ECOG 0-2
Life expectancy
Not specified
Hematopoietic
See Disease Characteristics
Hepatic
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Hepatitis B surface antigen negative
Hepatitis C antibody negative
Renal
Creatinine ≤ 1.5 times ULN
Immunologic
No active cytomegalovirus
No prior fludarabine-associated autoimmune hemolytic anemia or immune thrombocytopenic purpura
No active infection requiring treatment with antibiotic, antiviral, or antifungal agents
No prior significant allergic reaction to antibody therapies that required therapy to be discontinued
HIV negative
Other
No active secondary malignancy
No other concurrent severe diseases or mental disorders
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy
More than 4 weeks since prior alemtuzumab and/or rituximab
No prior bone marrow transplantation
No concurrent thrombopoietin or pegfilgrastim
Chemotherapy
More than 3 weeks since prior fludarabine
Endocrine therapy
Not specified
Radiotherapy
Not specified
Surgery
Not specified
Other
More than 3 months since prior investigational drugs
No other concurrent cytotoxic therapy
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There are 5 Locations for this study
Boston Massachusetts, 02115, United States
Jackson Mississippi, 39202, United States
New Brunswick New Jersey, 08903, United States
Pittsburgh Pennsylvania, 15224, United States
Pittsburgh Pennsylvania, 15232, United States
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