Lower But More Frequent Dose Rituximab to Treat Chronic Lymphocytic Leukemia
Condition: Refractory Chronic Lymphocytic Leukemia
MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will test the safety and effectiveness of using lower-dose rituximab given more
      frequently for treating chronic lymphocytic leukemia (CLL). Studies have shown that, used
      once a week for 4 weeks, rituximab was effective in up to 25 percent of patients with CLL.
      New evidence shows that using lower and more frequent doses of rituximab can be more
      effective in destroying leukemia cells and produce a better treatment response.

      Patients 21 years of age and older with CLL who have received treatment with fludarabine may
      be eligible for this study.

      Participants take rituximab for 12 weeks. One dose of the drug is infused through an arm vein
      over about 30 minutes on either day 1 (the first dose) or day 3 (the second dose). All other
      doses are given as an injection under the skin. After the first week, patients can choose to
      do these injections at home. Rituximab will be given 3 times a week for a total of 12 weeks.
      Other medications are given to reduce the side effects and allergic reactions to the drug. In
      addition to treatment, patients undergo the following tests and procedures:

      Before treatment

        -  Medical history, physical examination, electrocardiogram (EKG) and blood tests.

        -  Bone marrow and lymph node biopsies (surgical removal of a small tissue sample).

        -  Computed tomography (CT) and positron emission tomography (PET) scans. CT uses special
           x-rays to provide images of the neck, chest, abdomen and pelvis. PET uses a radioactive
           sugar to identify areas of disease.

      During treatment (study weeks 1-12)

        -  Medical history and physical examinations at weeks 3, 6 and 12 to evaluate drug side
           effects, plus weekly telephone checks and interim visits when needed.

        -  Blood tests every other week to evaluate blood counts.

      Evaluations after treatment (follow-up 3 months to 12 months)

        -  Blood tests at follow-up visits at 3, 6, 9 and 12 months after treatment to evaluate
           blood counts.

        -  Bone marrow aspiration and biopsy at 3 months after treatment to examine the effects of
           rituximab on bone marrow cells.

        -  CT scans of the neck, chest, abdomen and pelvis at 3, 6, 9 and 12 months after treatment
           to evaluate the response to treatment.
    

Detailed description: 
      Rituximab is FDA approved for the treatment of relapsed or refractory low grade or follicular
      CD20+ B cell non Hodgkin's lymphoma (375 mg/m(2) IV infusion once weekly for 4 or 8 doses).
      Recently, rituximab (anti CD20) has been introduced to CLL treatment regimens and has become
      an attractive choice in combination chemotherapy or as single agent treatment. Rituximab has
      been shown to be effective at lower doses than 375 mg/m(2) when given more frequently.

      Several theoretical considerations and supporting laboratory evidence suggest that a
      fractionated dosing schedule using low-dose rituximab could be more effective than the
      current i.v. schedule of high-dose rituximab. Indeed, preliminary clinical evidence suggests
      that low-dose rituximab at 20mg/m2 i.v. 3-times per week can lead to steady clearance of
      leukemic cells without inducing substantial loss of targeted CD20.

      This is a Phase I/II , single agent study which will evaluate the safety and feasibility of
      subcutaneous rituximab (Rituxan) administered at 20 mg/day three times a week for 12 weeks in
      subjects with CLL. Patients need to have had prior treatment with fludarabine, and have an
      elevated absolute lymphocyte count. The primary objective will be to test the safety and
      feasibility of giving rituximab subcutaneously. We will also obtain as a secondary endpoint
      an early estimate of efficacy as evidenced by (a) shrinkage of lymphadenopathy and/or (b)
      improvement in blood values and bone marrow biopsy findings.
    

Intervention name(s): Rituximab
Intervention type(s): Drug
Intervention MeSH terms: Rituximab
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: CLL; Monoclonal Antibody Therapy; Anti CD20; Biologic Response Modifier Therapy; Fractionated-Dose; Low-Dose; Chronic Lymphocytic Leukemia