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

Sponsored by:	Bayer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00086775

Purpose

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	Intervention	Phase
Leukemia	Drug: alemtuzumab Drug: fludarabine phosphate Drug: rituximab	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Fludarabine Fludarabine monophosphate Rituximab Alemtuzumab Campath

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control
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

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

July 2003

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086775

Locations

United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Mississippi
Jackson Oncology Associates, PLLC
Jackson, Mississippi, United States, 39202
United States, New Jersey
Cancer Institute of New Jersey at Robert Wood Johnson University Hospital
New Brunswick, New Jersey, United States, 08903
United States, Pennsylvania
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Western Pennsylvania Cancer Institute
Pittsburgh, Pennsylvania, United States, 15224

Sponsors and Collaborators

Bayer

Investigators

Study Chair:

John G. Gribben, MD, DSc

Dana-Farber Cancer Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000365631, BRLX-FLUCAM106, BRLX-STA1-03-058, OHSU-HEM-03050-P, DMS-F0334
Study First Received:	July 8, 2004
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00086775
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

refractory chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia

Study placed in the following topic categories:

Chronic lymphocytic leukemia
Leukemia, Lymphoid
Immunoproliferative Disorders
Rituximab
Leukemia, B-cell, chronic
Fludarabine monophosphate
Leukemia

Lymphatic Diseases
Leukemia, Lymphocytic, Chronic, B-Cell
Alemtuzumab
Fludarabine
Leukemia, B-Cell
Lymphoproliferative Disorders

Additional relevant MeSH terms:

Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immune System Diseases
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Physiological Effects of Drugs
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Antirheumatic Agents

ClinicalTrials.gov processed this record on January 15, 2009