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

Sponsor

Bayer (Industry)

Overall Status

Completed

CT.gov ID

NCT00086775

Collaborator

(none)

Locations

Duration (Months)

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Biological: alemtuzumab Biological: rituximab Drug: fludarabine phosphate	Phase 2

Detailed 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

Study Type:

Interventional

Allocation:

Randomized

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jul 1, 2003

Actual Primary Completion Date :

Jun 1, 2005

Actual Study Completion Date :

Oct 1, 2009

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
2	Jackson Oncology Associates, PLLC	Jackson	Mississippi	United States	39202
3	Cancer Institute of New Jersey at Robert Wood Johnson University Hospital	New Brunswick	New Jersey	United States	08903
4	Western Pennsylvania Cancer Institute	Pittsburgh	Pennsylvania	United States	15224
5	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232