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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00513747
First received: August 8, 2007
Last updated: July 1, 2016
Last verified: July 2016
  Purpose

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
Leukemia
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 Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Time to second treatment [ Time Frame: Every 3 months post-treatment until death or relapse ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of patients with mutated and unmutated IgVH genes [ Time Frame: Once at baseline ] [ Designated as safety issue: No ]

Enrollment: 84
Study Start Date: January 2008
Estimated Study Completion Date: December 2033
Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)
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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  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Eligibility Criteria for Pre-Registration:

  1. Patients must be within 6 months of the initial flow cytometric confirmation of B-cell chronic lymphocytic leukemia (CLL). This interval begins with the initial flow cytometric confirmation of disease.
  2. Clinical and immunophenotypic evidence of CLL including:

    2.1 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.
    • Additionally, the 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.

    2.2 Staging - Patients must be in the low category (i.e., only stages 0 or I) of the modified three-stage Rai staging system as described in the protocol.

  3. Patients should not have evidence of active disease as demonstrated by any of the following criteria:

    • Splenomegaly and/or massive/progressive lymphadenopathy that would require therapy
    • Presence of weight loss > 10% over the preceding 6 month period
    • Grade 2 or 3 fatigue
    • Fevers > 100.5°F or night sweats for greater than 2 weeks without evidence of infection
    • Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months.
  4. Prior Treatment: No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL.
  5. Age ≥ 18 years
  6. Performance Status 0 - 1.
  7. No HIV disease. Due to alterations in host immunity, patients known to have HIV infection may not be enrolled.
  8. Non-pregnant and non-nursing. Due to the unknown teratogenic potential of chemotherapy, pregnant or nursing women may not be enrolled. Women and men of reproductive potential should agree to use an effective means of birth control.
  9. Required Initial Laboratory Values:

    • Creatinine ≤ 1.5 x upper limit of normal

Eligibility Criteria for Registration (to Low-Risk Cohort or High-Risk Cohort Randomization between Early Intervention Versus Observation with Later Treatment)

  1. Successful determination of IgVH mutational status by reference laboratory.
  2. Absence of progression of CLL, i.e., absence of the following:

    • Progressive splenomegaly and/or lymphadenopathy on two independent measures spaced two weeks apart. If one assessment notes progression, this should be repeated prior to re-registration.
    • Development of anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/μL).
    • Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months.
    • Symptoms referable to CLL, including weight loss > 10% over the preceding 6 month period; grade 2 or 3 fatigue; or fevers > 100.5°F and/or night sweats for greater than 2 weeks without evidence of infection.
  3. Required Laboratory Value:

    • Creatinine ≤ 1.5 x upper limit of normal
  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
Alliance for Clinical Trials in Oncology
National Cancer Institute (NCI)
Investigators
Study Chair: John C. Byrd, MD Ohio State University
  More Information

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00513747     History of Changes
Other Study ID Numbers: CALGB-10501  U10CA031946  CDR0000537685 
Study First Received: August 8, 2007
Last Updated: July 1, 2016
Health Authority: United States: Federal Government

Keywords provided by Alliance for Clinical Trials in Oncology:
B-cell chronic lymphocytic leukemia
stage 0 chronic lymphocytic leukemia
stage I chronic lymphocytic leukemia

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

ClinicalTrials.gov processed this record on August 28, 2016