Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Objectives

Primary

1. 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

1. Compare the overall response rate in patients treated with these regimens.
2. Compare 1-year survival of patients treated with these regimens.
3. Compare time to progression in patients treated with these regimens.
4. Compare duration of response in patients treated with these regimens.
5. Compare the adverse event profile of these regimens in these patients.
6. Compare the molecular response rate in patients treated with these regimens.
7. Compare lymphocyte and lymphocyte subset recovery (CD3, CD3/CD4, CD3/CD8, CD20) in patients treated with these regimens.
8. Compare the time to complete response in patients treated with these regimens.
9. Compare the rate of cytomegalovirus reactivation and time to reactivation in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Diagnosis of B-cell chronic lymphocytic leukemia (CLL), defined as:
  • Peripheral lymphocyte count > 5,000/mm³
  • Clonal CD5-, CD19-, and CD23-positive lymphocytes

• Refractory to OR relapsed after prior first-line therapy

• No CNS involvement with CLL

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

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

Expected Enrollment

A total of 150 patients (75 per treatment arm) will be accrued for this study.

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.

Trial Contact Information

Trial Lead Organizations

Berlex Incorporated

Ann LaCasce, MD, Protocol chair		Ph: 617-632-5959; 866-790-4500

Registry Information
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
Trial Start Date		2003-07-11
Trial Completion Date		2005-06-15
Registered in ClinicalTrials.gov		NCT00086775
Date Submitted to PDQ		2004-04-07
Information Last Verified		2009-10-22

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