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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00086775
Recruitment Status : Completed
First Posted : July 12, 2004
Last Update Posted : August 2, 2013
Information provided by:
National Cancer Institute (NCI)

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:



  • 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.


  • 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 Type : Interventional  (Clinical Trial)
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 : July 2003
Actual Primary Completion Date : June 2005
Actual Study Completion Date : October 2009

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • See Disease Characteristics


  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative


  • Creatinine ≤ 1.5 times ULN


  • 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


  • 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


Biologic therapy

  • More than 4 weeks since prior alemtuzumab and/or rituximab
  • No prior bone marrow transplantation
  • No concurrent thrombopoietin or pegfilgrastim


  • More than 3 weeks since prior fludarabine

Endocrine therapy

  • Not specified


  • Not specified


  • Not specified


  • More than 3 months since prior investigational drugs
  • No other concurrent cytotoxic therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00086775

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
Western Pennsylvania Cancer Institute
Pittsburgh, Pennsylvania, United States, 15224
Hillman Cancer Center at University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Study Chair: Ann S. LaCasce, MD Dana-Farber Cancer Institute Identifier: NCT00086775     History of Changes
Other Study ID Numbers: BRLX-FLUCAM106
CDR0000365631 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: July 12, 2004    Key Record Dates
Last Update Posted: August 2, 2013
Last Verified: October 2009

Keywords provided by National Cancer Institute (NCI):
refractory chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Antiviral Agents
Anti-Infective Agents