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

Leukemia Clinical Trial

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

Status Completed

Clinical Trial 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 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.

Clinical Trial 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. ;

Study Design

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

• NCT number: NCT00086775
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Completed
• Phase: Phase 2
• Start date: July 2003
• Completion date: October 2009