Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): DNA Microarray Gene Expression Analysis
- Due to their synergistic action and non-overlapping toxicity profiles, the combination
of Rituximab and Fludarabine is the treatment of choice for advanced stage chronic
lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL).
- As such, we have designed this protocol to better understand the genetic basis of
CLL/SLL, to identify predictors of treatment response and to study the molecular
effects of Rituximab Fludarabine on the leukemic cells.
- A new technology utilizing complementary deoxyribonucleic acid (cDNA) microarrays now
permits the simultaneous quantitation of the expression of thousands of genes; this
methodology can evaluate defined cellular pathways, and also discover novel genes
influencing cell biology.
- In addition to improving our understanding of the pathogenesis of CLL/SLL, these
molecular studies may identify new therapeutic targets in CLL/SLL, and may help to
identify those CLL/SLL patients most likely to respond to the combination of
Fludarabine and Rituximab.
- Evaluate CLL/SLL patients during and following Rituximab Fludarabine chemotherapy for
changes in lymphocyte gene expression using DNA microarray analysis.
- Evaluate gene expression by DNA microarray analysis of leukemic cells in blood, bone
marrow and lymph nodes.
- Low, Intermediate or High-Risk Category of CLL/SLL, using the Modified Three- Stage Rai
- Age greater than or equal to 18 years.
- Patients must have received no previous cytotoxic or monoclonal antibody therapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
- Patients must not be pregnant or breast-feeding.
- Patients with active autoimmune hemolytic anemia (AIHA)) grade III or higher
(transfusion or steroids indicated) or immune thrombocytopenia (ITP) grade III or
higher (platelets less than 50,000/microL) shall not be enrolled.
- Any patient with a medical condition that requires chronic use of corticosteroids shall
not be enrolled.
- Patients who do not require treatment will be followed every 3-6 months and will donate
cellular products, bone marrow biopsies, bone marrow aspirates and/or lymph nodes for
- Patients who do require treatment will received the standard dose of the Rituximab
monoclonal antibody and the standard dose of Fludarabine for a total of six cycles. In
the first cycle, Rituximab will be given on day 1 with Fludarabine being given on days
2-6. This will allow for appropriate samplings of the effects of Rituximab on
lymphocytes before during and at the end of the first 24 hours. In subsequent cycles
2-6, the Rituximab and day 1 Fludarabine can both be given on day 1.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Change in Gene Expression Post Chemo
Changes in lymphocyte gene expression was measured by deoxyribonucleic acid (DNA) microarray analysis of circulating leukemic cells after completion of study treatment. A change in expression is defined as a >50% increase in circulating leukemic cells or a 30% decrease in circulating leukemic cells.
6 hours post treatment, and 24 hours post treatment
Wyndham H Wilson, M.D.
National Cancer Institute, National Institutes of Health
United States: Federal Government
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