Early or Delayed Fludarabine and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Cancer and Leukemia Group B
ClinicalTrials.gov Identifier:
First received: August 8, 2007
Last updated: November 3, 2011
Last verified: November 2011

RATIONALE: Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving fludarabine together with rituximab may kill more cancer cells. Sometimes the cancer may not need treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether giving fludarabine together with rituximab early is more effective than giving fludarabine and rituximab after observation in treating chronic lymphocytic leukemia.

PURPOSE: This randomized phase III trial is studying fludarabine and rituximab to compare how well they work when given early or after observation in treating patients with previously untreated chronic lymphocytic leukemia.

Condition Intervention Phase
Biological: rituximab
Drug: fludarabine phosphate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase III Intergroup CLL Study of Asymptomatic Patients With Untreated Chronic Lymphocytic Leukemia Randomized to Early Intervention Versus Observation With Later Treatment in the High Risk Genetic Subset With IGVH Unmutated Disease

Resource links provided by NLM:

Further study details as provided by Cancer and Leukemia Group B:

Enrollment: 84
Study Start Date: January 2008
Estimated Study Completion Date: December 2033
Arms Assigned Interventions
Experimental: Arm I
Patients receive rituximab IV over 4 hours on days 1, 3, and 5 of week 1 and then on day 1 of weeks 5, 9, 13, 17, and 21. Patients also receive fludarabine phosphate IV over 30 minutes on days 1-5 of weeks 1, 5, 9, 13, 17, and 21. After completion of chemoimmunotherapy, patients are followed every 3 months until disease progression. At the time of disease progression, patients receive retreatment with chemoimmunotherapy as above or another treatment regimen.
Biological: rituximab
Given IV over 4 hours
Drug: fludarabine phosphate
Given IV over 30 minutes
Active Comparator: Arm II
Patients are followed every 3 months until disease progression. At the time of disease progression, patients receive rituximab and fludarabine phosphate as in arm I. Patients are then followed every 3 months until second disease progression. Patients with a second disease progression receive retreatment with chemoimmunotherapy as above or another treatment regimen.
Biological: rituximab
Given IV over 4 hours
Drug: fludarabine phosphate
Given IV over 30 minutes

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


  • Clinical and immunophenotypic evidence of B-cell chronic lymphocytic leukemia (CLL) diagnosed within the past 6 months AND meets the following criteria:

    • An absolute lymphocytosis of > 5,000/μL
    • Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes
    • Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the absence of other pan-T-cell markers

      • B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density
      • Patients with bright surface immunoglobulin levels must have CD23 coexpression and absence of t(11;14) on interphase cytogenetics or have negative tumor protein staining for cyclin D1
  • Low-risk category (i.e., only stages 0 or I) of the modified three-stage Rai staging system
  • No evidence of active or progressive disease as demonstrated by any of the following:

    • Massive or progressive splenomegaly and/or lymphadenopathy that requires therapy
    • Progressive lymphocytosis with an increase of > 50% over a 2-month period or an anticipated doubling time of less than 6 months
    • Presence of weight loss > 10% over the preceding 6-month period
    • Grade 2 or 3 fatigue
    • Fevers > 100.5°F and/or night sweats for greater than 2 weeks without evidence of infection
    • Development of anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/μL)
  • Must have undergone IgV_H mutation testing and be classified according to the following:

    • Genetically low-risk disease

      • IgV_H mutated
      • Less than 98% IgV_H homology
    • Genetically high-risk disease

      • IgV_H unmutated
      • At least 98% IgV_H homology


  • Performance status 0-1
  • Creatinine ≤ 1.5 times upper limit of normal
  • No HIV disease
  • Not pregnant or nursing
  • Fertile patients must use effective contraception


  • No prior therapy for CLL, including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL
  • No concurrent hormones or other chemotherapy except for steroids for hypersensitivity reactions or new adrenal failure (chronic requirement for steroids is an exclusion criterion for this study) or hormones for non-disease-related conditions (e.g., insulin for diabetes)
  • No concurrent palliative radiotherapy
  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: NCT00513747

  Show 387 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Study Chair: John C. Byrd, MD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00513747     History of Changes
Other Study ID Numbers: CDR0000537685, U10CA031946, CALGB-10501
Study First Received: August 8, 2007
Last Updated: November 3, 2011
Health Authority: United States: Federal Government

Keywords provided by Cancer and Leukemia Group B:
B-cell chronic lymphocytic leukemia
stage 0 chronic lymphocytic leukemia
stage I 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
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on October 16, 2014