Protocol for the Treatment of Patients With Previously Untreated Chronic Lymphocytic Leukemia
Condition: Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Intervention: Fludarabine; Cyclophosphamide; Rituximab
Intervention description: Fludarabine is usually administered by IV infusion over 30 minutes or longer.; The dosage is a solution of 20 mg/mI. IV infusion over 1 hour.; First Infusion: The rituximab solution for infusion should be administered intravenously at an initial rate of 50 mg/hr. Subsequent rituximab infusions can be administered at an initial rate of 100 mg/hr, and increased by 100 mg/hr increments at 30-minute intervals, to a maximum of 400 mg/hr as tolerated.
Intervention MeSH terms: Cyclophosphamide; Rituximab; Fludarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 65.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Chronic; Lymphocytic; Leukemia; Fludarabine; Cyclophosphamide; Rituximab

Summary:

      This research study will look at the effects (good or bad) of administering cyclophosphamide,
      fludarabine, and rituximab. Clinical studies with combination therapy have shown higher
      response rates than using single drugs, and this study will evaluate the side effects and
      effectiveness of this combination.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of CD20 + CLL

          -  Peripheral blood absolute lymphocyte count of > 5,000/mm3 obtained within 2 weeks
             prior to randomization.

          -  The lymphocytosis must consist of small to moderate size lymphocytes, with ≤55% (no
             greater than 55%) prolymphocytes, atypical lymphocytes, or lymphoblasts
             morphologically.

          -  Phenotypically characterized CD20 + CLL defined as: 1) the predominant population of
             cells share B-cell antigens with CD5 in the absence of other pan-T-celI markers (CD3,
             CD2, etc.); 2) B-cell expresses either kappa or lambda light chains; and 3) surface
             immunoglobulin (slg) with low-cell surface density expression.

          -  Splenomegaly, hepatomegaly or lymphadenopathy are not required for the diagnosis of
             CLL.

          -  Must require chemotherapy. Indications for chemotherapy are one or more of the
             following:

          -  One or more of the following disease-related symptoms

          -  Weight loss >10% within the previous 6 months.

          -  Fevers of greater than 100.0° F for 2 weeks without evidence of infection.

          -  Night sweats without evidence of infection.

          -  Evidence of progressive marrow failure as manifested by the development of or
             worsening of anemia (< 10 g/dl) and/or thrombocytopenia (< 100,000/mm3).

          -  Massive (i.e., > 6 cm below left costal margin) or progressive splenomegaly.

          -  Massive nodes or clusters (i.e., > 10 cm in longest diameter) or progressive

          -  adenopathy.

          -  Progressive lymphocytosis with an increase of> 50% over 2 month period, or an
             anticipated doubling time of less than 6 months.

          -  NOTE: Marked hypogammaglobulinemia or the development of a monoclonal protein in the
             absence of any of the above criteria for active disease are not sufficient for
             protocol therapy.

          -  Serum creatinine <1.5 mg/dl.

          -  Bilirubin must be <2 mg/dl, unless secondary to tumor, obtained within 2 weeks prior
             to randomization.

          -  Age >18 years.

          -  Not pregnant (confirmed by serum pregnancy test in females of reproductive potential)
             or breast feeding, because it is unknown what effect these drugs will have on
             children.

          -  ECOG performance status 0-2.

          -  AST or ATL >2x upper limit of normal unless related to CLL.

          -  Subject has provided written informed consent.

        Exclusion criteria:

          -  Subjects with autoimmune anemia or thrombocytopenia are not eligible.

          -  No prior cytotoxic chemotherapy. Patients with a history of steroid treatment for CLL,
             autoimmune hemolytic anemia, or autoimmune thrombocytopenia are not eligible.

          -  Subjects with active infections requiring oral or intravenous antibiotics until
             resolution of the infection and completion of therapeutic antibiotics.

          -  Women of childbearing potential and sexually active males who refuse to use an
             accepted and effective method of contraception.

          -  Subjects with a second malignancy other than basal cell carcinoma of the skin or in
             situ carcinoma of the cervix are not eligible unless the tumor was treated with
             curative intent at least two years previously.

          -  History of HIV

          -  CNS disease

          -  History of psychiatric disorder that would make it difficult to enroll and follow the
             patient on trial.

          -  New York Heart Classification III or IV heart disease.

          -  Hepatitis BsAg or Hepatitis C positive.