Clinical trial NCT00001586
Conditions: Chronic Lymphocytic Leukemia
Keywords: Genetics Bone Marrow Transplantation Immunosuppression T Lymphocytes Marrow Purging
Sponsor: National Cancer Institute (NCI)
Start date: 1997-09-01; Completion date: 2011-11-01
Enrollment: 105 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Background:

* Combined therapy with rituximab and fludarabine is the treatment of choice for advanced stage chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
* A new technology called deoxyribonucleic acid (DNA) microarray can be used to gain knowledge about the genetic basis of CLL/SLL.
* Genetic studies of CLL/SLL may improve our understanding of what happens in the disease, help determine which patients are most likely to respond to treatment with fludarabine and rituximab, and identify new treatments.

Objectives:

-To gain further knowledge about CLL/SLL and the role of rituximab and fludarabine in treating the disease.

Eligibility:

-Patients 18 years of age and older with low, intermediate or high-risk CLL/SLL.

Design:

* Patients with low-risk CLL/SLL do not receive treatment, but are followed every 3 to 6 months and donate cells (through apheresis) or lymph nodes, or both, for research purposes.
* Patients with intermediate or high-risk CLL/SLL receive standard treatment with rituximab and fludarabine for six 28-day treatment cycles. Rituximab is given on day 1 and fludarabine is given on days 1-5. (For the first cycle only, fludarabine treatment starts on day 2. This delay permits blood sampling on day 1 for the effect of rituximab on white blood cells.)
* Laboratory tests and imaging studies are done periodically to monitor drug side effects and the response to treatment. Tests include bone marrow biopsy and aspiration, blood tests and x-rays, including positron emission tomography (PET) and computed tomography (CT) scans.

Detailed description:
Background:

* 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.

Objectives:

* 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.

Eligibility:

* Low, Intermediate or High-Risk Category of CLL/SLL, using the Modified Three- Stage Rai Staging System
* 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.

Design:

* 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 research purposes.
* 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.

Arms: arm 1: Previously untreated low or intermediate risk B-cell chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL) patients (pts) not requiring chemotherapy. No rituximab fludarabine administered. Eligible to donate cells. arm 2: Previously untreated intermediate or high risk B-cell chronic lymphocytic lymphoma (CLL)/small lymphocytic lymphoma (SLL) patients requiring chemotherapy. Rituximab 375 mg/m\^2 by infusion on day 1, cycle 1 followed by fludarabine on day 2-6, 25 mg/m\^2 day x 5 days administered as an intravenous push or intravenous piggyback over 10-30 minutes, repeated every 28 days.
Interventions: intervention 1: Rituximab intervention 2: Fludarabine phosphate intervention 3: Leukemic or stroma cells
Intervention descriptions: intervention 1: Rituxan intervention 2: Fludara intervention 3: Patients are eligible to donate cells for the purpose of analyzing leukemic cells. Cells can be donated by apheresis (e.g. 60-90 minute intravenous technique), lymph node biopsy (e.g. 3 biopsy/excision of lymph nodes)bone marrow biopsy (e.g. 2-4 separate bone marrow biopsies), and bone marrow aspiration (e.g. 3 to 5cc of marrow per aspirate).

Protocol documents: