FCR Plus Sargramostim (GM-CSF) as Frontline Therapy for Symptomatic Chronic Lymphocytic Leukemia
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Cyclophosphamide; Fludarabine; Sargramostim; Rituximab
Intervention description: Course 1: 250 mg/m^2 by vein over 5-30 minutes on Days 2, 3, and 4; Course 2 - 6: 250 mg/m^2 by vein over 5-30 minutes on Days 1 - 3; Course 1: 25 mg/m^2 by vein over 5-30 minutes on Days 2,3, and 4; Course 2 - 6: 25 mg/m^2 by vein over 5-30 minutes on Days 1 - 3; Course 1: 250 mcg/m^2 subcutaneous (SQ) on Days -1 and Days 5 - 11; Course 2 - 6: 250 mcg/m^2 SQ on Days -1 and Days 4 - 10; Course 1: 375 mg/m^2 by vein over 2-6 Hours on Day 1; Course 2 - 6: 500 mg/m^2 by vein over 2-6 Hours on Day 1
Intervention MeSH terms: Cyclophosphamide; Rituximab; Fludarabine; Fludarabine phosphate; Sargramostim
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Healthy volunteers: No
Keywords: Chronic Lymphocytic Leukemia; Leukemia; Cyclophosphamide; Fludarabine; Sargramostim; Rituximab; GM-CSF; FCR

Summary:

      The goal of this clinical research study is to learn if using a combination of fludarabine,
      cyclophosphamide, and rituximab, with sargramostim (GM-CSF) can help to control previously
      untreated chronic lymphocytic leukemia (CLL). The safety of this combination will also be
      studied. This study will evaluate antibody-dependent cellular cytotoxicity (ADCC) and its
      relationship to response.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Untreated CLL, CLL/PLL, or SLL (small lymphocytic lymphoma) with indication for
             therapy. Indications for therapy include at least one of the following: (1) one or
             more disease-related symptoms [fever, night sweats, weight loss > 10% in prior 6
             months, pronounced fatigue]; (2) advanced stage disease (Rai stage >/= 3 or Binet
             stage C); (3) autoimmune anemia and/or thrombocytopenia that is unresponsive to other
             therapies; (4) massive or progressive hepatomegaly and/or splenomegaly and/or
             lymphadenopathy; (5) recurrent infections; (6) rapid lymphocyte doubling time of < 6
             months.

          -  Patients who have been treated with not more than one regimen of immunotherapy (e.g.
             rituximab, alemtuzumab, rituximab plus alemtuzumab) for a diagnosis of CLL, CLL/PLL,
             or SLL (small lymphocytic lymphoma).

          -  Beta-2-microglobulin </= 4 mg/dL.

          -  Adequate liver function (total bilirubin </= 2.5 mg/dL, serum glutamate pyruvate
             transaminase (SGPT) </=4 x ULN) and renal function (serum creatinine </= 2.0 mg/dL
             and/or creatinine clearance < 30 mL/hour). Patients with renal or liver dysfunction
             due to suspected organ infiltration by lymphocytes may be eligible after discussion
             with the Principal Investigator, but upper limits for creatinine even under these
             circumstances must be creatinine < 3mg/dL and bilirubin < 6 mg/dL. Patients with
             Gilbert's syndrome may be entered on study with bilirubin levels </= 4 mg/dL.

          -  Eastern Cooperative Oncology Group (ECOG) performance status </= 2.

          -  Signed informed consent in keeping with the policies of the hospital.

          -  Male and female patients who are fertile agree to use an effective barrier method of
             birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy.
             Female patients of childbearing potential (non-childbearing is defined as >/= 1 year
             after menses cease and/or surgically sterilized) need a negative serum or urine
             pregnancy test within 2 days of study enrollment..

        Exclusion Criteria:

          -  Active hepatitis B (at least one of the following markers positive: HBsAg, hepatitis B
             e antigen (HBeAg), immunoglobulin M (IgM) anti-HBc, hepatitis B virus (HBV) DNA).

          -  Concurrent chemotherapy or immunotherapy.

          -  Pregnant patients.

          -  History of HIV

          -  Symptomatic central nervous system (CNS) disease