Lower But More Frequent Dose Rituximab to Treat Chronic Lymphocytic Leukemia
Lower But More Frequent Dose Rituximab to Treat Chronic Lymphocytic Leukemia
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.
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.
-  INCLUSION CRITERIA

 -  Patients diagnosed with Chronic Lymphocytic Leukemia

 -  Prior therapy with fludarabine or a fludarabine containing regimen

 -  CD20 expression on CLL cells

 -  Neutrophil count ANC greater than 500/mm(3)

 -  Platelet count greater than 30K/mm(3)

 -  Age 21-99

 EXCLUSION CRITERIA

 -  Bulky lymphadenopathy, defined as greater than 1 lymph node with greater than 5cm in
 largest diameter

 -  Evidence for transformation into high grade lymphoma (Richter's transformation)

 -  ECOG performance 3 or higher

 -  Other concurrent anticancer therapies

 -  Less than 3 months from last systemic therapy for CLL

 -  Less than 6 months from last monoclonal antibody therapy

 -  More than 10 doses rituximab, within 12 months preceeding protocol enrollment, either
 as single agent or in a combination chemotherapy regimen

 -  Chronic or current clinically significant infection, including HIV positivity or
 hepatitis C

 -  Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary,
 infectious, or metabolic disease of such severity that it would preclude the patient's
 ability to tolerate protocol therapy

 -  History of mucocutaneous reactions (paraneoplastic pemphigus, Stevens-Johnson
 syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal
 necrolysis)

 -  Known anaphylaxis or IgE mediated hypersensitivity to murine proteins or to any
 component of this product

 -  Inability to self inject the study medication or to have it administered by a third
 person

 -  Inability to understand the investigational nature of the study ability to provide
 informed consent