FCM-R (Fludarabine, Cyclophosphamide, Mitoxantrone, Rituximab) in Previously Untreated Patients With Chronic Lymphocytic Leukemia (CLL) < 70 Years
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Fludarabine; Cyclophosphamide; Mitoxantrone; Rituximab; Filgrastim
Intervention description: Fludarabine 25 mg/m2 on Days 2,3,4 i.v. 5-30 mins for course 1, and on Days 1 - 3 for courses 2 - 6; Cyclophosphamide 250 mg/m2 on Day 2,3,4 i.v. 5-30 mins for course 1, and on Days1 - 3 for courses 2 - 6.; Mitoxantrone 6 mg/m2 on Day 2 i.v. 30-60 mins for course 1, and on Day 1 for courses 2 - 6.; Rituximab 375 mg/m2 on Day 1 i.v. 2-6 hours for course 1 and 500 mg/m2 on Day 1 for courses 2 - 6.; Pegylated Filgrastim - 6 mg on Day 4,s.c. for course 1 and on Day 3 for courses 2 - 6.
Intervention MeSH terms: Cyclophosphamide; Rituximab; Fludarabine; Mitoxantrone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Chronic Lymphocytic Leukemia; Untreated; Fludarabine; Fludara; Cyclophosphamide; Cytoxan; Mitoxantrone; Novantrone; Rituximab; Rituxan; Pegylated Filgrastim; Neupogen

Summary:

      The goal of this clinical research study is to learn if using a combination of fludarabine,
      cyclophosphamide, and mitoxantrone plus rituximab, with the growth factor pegylated
      filgrastim, will improve the response to treatment, and increase the time this response
      lasts, for patients with previously untreated CLL. The safety of this combination will also
      be studied.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Untreated CLL, CLL/ prolymphocytic leukemia (PLL), or small lymphocytic lymphoma (SLL)
             with indication for therapy (Indications for therapy include at least one of the
             following: i) one or more disease-related symptoms [fever, night sweats, weight loss,
             pronounced fatigue]; ii) advanced stage disease (Rai stage >/= 3 or Binet stage C);
             iii) autoimmune anemia and/or thrombocytopenia that is unresponsive to other
             therapies; iv) massive or progressive hepatomegaly and/or splenomegaly and/or
             lymphadenopathy; iv) recurrent infections; v) rapid lymphocyte doubling time of < 6
             months).

          2. Age < 70 years.

          3. 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).
             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.

          4. Beta-2-microglobulin </= 4 mg/dL.

          5. Eastern Cooperative Oncology Group (ECOG) performance status </= 2.

          6. Signed informed consent in keeping with the policies of the hospital.

          7. 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
             postmenopausal or surgically sterilized) need a negative serum or urine pregnancy test
             within 14 days of study enrollment.

        Exclusion Criteria:

          1. Active hepatitis B (at least one of the following markers positive: HBsAg, HBeAg,
             Immunoglobulin M (IgM) hepatitis B core antibody (anti-HBc), Hepatitis B (HBV) DNA).

          2. Concurrent chemotherapy or immunotherapy.

          3. Pregnant patients.

          4. History of HIV

          5. Symptomatic central nervous system (CNS) disease

          6. Symptomatic heart disease (NYHA class >/= 3) or left ventricle (LV) ejection fraction
             < 40% (by multiple gated acquisition scan (MUGA) or echocardiogram)