Fludarabine Combined With Either Alemtuzumab or Rituximab in Treating Patients With Refractory or Relapsed B-Cell Chronic Lymphocytic Leukemia

Official Title: “Phase II Trial Comparing Combination Treatment With Fludarabine and Alemtuzumab to Fludarabine and Rituximab in Patients With B-Cell Chronic Lymphocytic Leukemia Requiring Treatment After First Line Therapy”

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 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.

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.

Intervention(s) in this Clinical Trial

• Biological: alemtuzumab
• Biological: rituximab
• Drug: fludarabine phosphate

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Bayer Industry

Overall Clinical Trial Officials and Contacts

Ann S. LaCasce, MD Study Chair Dana-Farber Cancer Institute  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00086775

Study ID Number: CDR0000365631

ClinicalTrials.gov Identifier: NCT00086775

Health Authority: United States: Federal Government

Clinical trial summary from the National Cancer Institute's PDQ® database