Fludarabine and Cyclophosphamide With or Without Rituximab in Patients With Previously Untreated Chronic B-Cell Lymphocytic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Rituximab; Cyclophosphamide; Fludarabine Phosphate
Intervention description: Intravenous repeating dose; Intravenous repeating dose; Intravenous repeating dose
Intervention MeSH terms: Cyclophosphamide; Rituximab; Fludarabine; Fludarabine phosphate
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 817.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: B-cell chronic lymphocytic leukemia; stage I chronic lymphocytic leukemia; stage II chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia

Summary:

      This randomized phase III trial is studying fludarabine, cyclophosphamide, and rituximab to
      see how well they work compared to fludarabine and cyclophosphamide in treating patients with
      B-cell chronic lymphocytic leukemia.
    

Eligibility criteria:

        DISEASE CHARACTERISTICS:

          -  Diagnosed B-cell chronic lymphocytic leukemia (CLL) defined by the National Cancer
             Institute (NCI) Working Group criteria

          -  Meets 1 of the following criteria:

               -  Binet stage C disease

               -  Binet stage B disease AND ≥ 1 of the following signs or symptoms*:

                    -  B symptoms (night sweats, weight loss ≥ 10% within the previous 6 months,
                       fevers > 38°C or 100.4°F for ≥ 2 weeks without evidence of infection), or
                       constitutional symptoms (fatigue)

                    -  Continuous progression (doubling of peripheral lymphocyte count within the
                       past 6 months and absolute lymphocyte count > 50 G/I)

                    -  Evidence of progressive marrow failure as manifested by the
                       development/worsening of anemia and/or thrombocytopenia

                    -  Massive, progressive or painful splenomegaly or hypersplenism

                    -  Massive lymph nodes or lymph node clusters (> 10 cm in longest diameter),
                       danger of organ complications through large lymphoma (e.g., vascular
                       compression or tracheal narrowing), or progressive lymphadenopathy

                    -  Occurrence of symptomatic hyperviscosity problems at leukocyte counts > 200
                       G/I (symptomatic leukostasis) NOTE: * Marked hypogammaglobulinemia or the
                       development of a monoclonal protein in the absence of any of the above
                       criteria for active disease is not sufficient for eligibility

          -  No Binet stage A disease

          -  No transformation to an aggressive B-cell malignancy (e.g., diffuse large cell
             lymphoma, Richter's syndrome, or prolymphocytic leukemia)

        PATIENT CHARACTERISTICS:

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-1

          -  Cumulative Illness Rating Scale (CIRS) score > 6

          -  Life expectancy > 6 months

          -  Bilirubin ≤ 2 times upper limit of normal (ULN)

          -  Alkaline phosphatase and transaminases ≤ 2 times ULN

          -  Creatinine clearance ≥ 70 mL/min

          -  Not pregnant or nursing

          -  Negative pregnancy test

          -  Fertile patients must use effective contraception during and for 2 months after study
             treatment

          -  No known hypersensitivity with anaphylactic reaction to humanized monoclonal
             antibodies or any of the study drugs

          -  No cerebral dysfunction that precludes chemotherapy

          -  No active bacterial, viral, or fungal infection

          -  No clinically significant autoimmune cytopenia or Coombs-positive hemolytic anemia

          -  No other active malignancy requiring concurrent treatment except basal cell carcinoma
             or tumors treated curatively by surgery

          -  No medical or psychological condition that would preclude study therapy

          -  No concurrent disease that requires prolonged (> 1 month) therapy involving
             glucocorticoids

        PRIOR CONCURRENT THERAPY:

          -  No previous treatment of CLL by chemotherapy, radiotherapy, or immunotherapy