Fludarabine, Cyclophosphamide, and Rituximab in Treating Patients Who Have Chronic Lymphocytic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: filgrastim; rituximab; cyclophosphamide; fludarabine phosphate
Intervention description: Filgrastim (300 μg for patients ≤ 70 kg or 480 μg for patients > 70 kg) will be administered beginning two days after each cyclophosphamide dose and given for a total of eight subcutaneous daily doses.; Approximately four weeks after the completion of the last cyclophosphamide dose, patients will receive rituximab 375mg/m2 as an intravenous infusion once weekly for four doses.; Cyclophosphamide 3000mg/m2 will be given intravenously q 2 - 3 weeks x 3 doses.; Fludarabine will be administered intravenously at a dose of 25 mg/m2 per day x 5 days every 4 weeks.
Intervention MeSH terms: Cyclophosphamide; Rituximab; Fludarabine; Fludarabine phosphate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia

Summary:

      RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
      so they stop growing or die. Combining more than one drug may kill more cancer cells.
      Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing
      substances to them without harming normal cells.

      PURPOSE: Phase II trial to study the effectiveness of fludarabine plus high-dose
      cyclophosphamide and rituximab in treating patients who have previously untreated chronic
      lymphocytic leukemia.
    

Eligibility criteria:

        Inclusion criteria:

          -  Patients must have either intermediate or high-risk chronic lymphocytic leukemia as
             defined by the three-stage Rai system (see section 2.2 page 2). Patients with Rai
             intermediate risk disease should meet the criteria for active disease as outlined by
             the NCI Working Group guidelines (including weight loss, fatigue, fevers, evidence of
             progressive marrow failure, splenomegaly, progressive lymphadenopathy, or progressive
             lymphocytosis with a rapid doubling time).

          -  Patients must be previously untreated (with cytoreductive agents) for their CLL.

          -  The patient must have an absolute lymphocytosis in the blood of at least 5,000
             lymphocytes/μl, or bone marrow lymphocytosis greater than or equal to 30% of all
             nucleated cells. These lymphocytes must have an appropriate immunophenotype for CLL
             including expression of CD5 and CD20.

          -  Karnofsky performance status equal to or greater than 60% (see Appendix B).

          -  Eligible patients should have a reasonable life-expectancy greater than four weeks.

          -  Age ≥ 18 years and ≤ 75 years.

          -  Total bilirubin ≤ 2.0 mg per deciliter. Total creatinine ≤ 2.0 mg/ dl.

          -  Platelet count ≥ 50,000/ ul.

          -  Signed informed consent, which indicates the investigational nature of this, is
             required.

          -  No patient may be entered onto the study without consultation with the principal
             investigator.

        EXCLUSION CRITERIA:

          -  Patients with Rai intermediate risk disease who meet the criteria of Montserrat
             "smouldering leukemia" will not be eligible for treatment on this protocol.

          -  Patients with significant autoimmune hemolytic anemia or autoimmune thrombocytopenia
             shall not be eligible for treatment on this protocol as there is some evidence that
             fludarabine can worsen these conditions.

          -  Patients with active infections requiring systemic antibiotics.

          -  Prior cytotoxic treatment of their CLL.

          -  Pregnant or lactating women. Women and men of childbearing age should use effective
             contraception.

          -  Patients with a serious cardiac condition.

          -  Concomitant chemotherapy or radiotherapy while on protocol.

          -  Concomitant prednisone therapy will not be permitted as the combination of fludarabine
             and prednisone is known to increase the risk of opportunistic infections. Patients may
             receive intravenous immunoglobulin (IVIG) and other supportive care measures as
             clinically appropriate while on protocol.