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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00086775
First received: July 8, 2004
Last updated: August 1, 2013
Last verified: October 2009
  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
Biological: alemtuzumab
Biological: rituximab
Drug: fludarabine phosphate
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: 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

Resource links provided by NLM:


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

Study Start Date: July 2003
Study Completion Date: October 2009
Primary Completion Date: June 2005 (Final data collection date for primary outcome measure)
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
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, see Learn About Clinical Studies.

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: Ann S. LaCasce, MD Dana-Farber Cancer Institute
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00086775     History of Changes
Other Study ID Numbers: BRLX-FLUCAM106, CDR0000365631, BRLX-STA1-03-058, OHSU-HEM-03050-P, DMS-F0334
Study First Received: July 8, 2004
Last Updated: August 1, 2013
Health Authority: United States: Federal Government

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

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

ClinicalTrials.gov processed this record on August 28, 2014