Etanercept and Rituximab in Patients With Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Study Overview
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Brief Summary
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This is a phase I/II study of the combination of etanercept and rituximab in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). This combination is proposed to improve the efficacy and diminish the toxicity of this the

Detailed Description
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Rationale: Previous research has demonstrated that rituximab has efficacy against chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Rituximab is a monoclonal antibody used to treat different types of lymphomas. Monoclonal antibodies are a type of immunotherapy used against some types of cancer. They are produced in a laboratory and designed to target as well as bind with cells that carry specific proteins. Rituximab attaches to a protein called CD20 that is found almost exclusively on the surface of B-cells. Once rituximab attaches to the protein, the immune system activates to kill the malignant B-cells. Researchers are investigating what other therapies to combine with rituximab to reduce side effects and improve patient outcomes. The current study combines etanercept with rituximab. Etanercept is an anti-inflammatory agent being tested as a therapy for cancer. Researchers want to assess the theory that etanercept may reduce the toxicity associated with rituximab in patients and increase efficacy while providing its own treatment benefit to patients. Purpose: This study is evaluating the safety and efficacy of combination etanercept and rituximab in patients with CLL and SLL. The biological response of tumor cells and the immune system to this drug combination will also be measured in patients before, during, and after therapy administration. Treatment: Patients in this study will receive etanercept and rituximab. Etanercept is given through injections into the skin and rituximab through intravenous infusions. During the first week of the study, etanercept alone will be given to patients two times. During the second week, patients will continue receiving etanercept twice weekly and begin receiving rituximab three times weekly. This schedule of etanercept twice weekly and rituximab three times weekly will be repeated four times. Several tests and exams will be given throughout the study to closely monitor patients. Treatments will be discontinued due to disease growth or unacceptable side effects.

Official Title
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Phase I/II Study of Etanercept and Rituximab in Patients With Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Conditions
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Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Intervention / Treatment
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* Drug: Etanercept
* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have been previously treated CLL/SLL Must have CD20 expression ECOG PS =<3 No prior Campath-1H No active infection requiring antibiotics No concurrent immunosuppressive therapy No prior history demyelinating neurologic disease No active viral hepatitis Exclusion Criteria: No pregnant or breastfeeding women ECOG PS =4 Life expectancy of >12 weeks Patients with bilirubin or creatinine>3.0 mg/dl

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Etanercept 25 mg administered sub-cutaneously twice weekly (Monday and Thursday) weeks 1-5 of therapy (total of 10 doses). The third dose of etanercept will be administered 1 hour prior to receiving rituximab. Rituximab: Patients will receive 375 mg/M2 of rituximab three times weekly for four weeks (a total of 12 doses of rituximab). | Drug: Etanercept<br>* 25 mg SQ twice weekly weeks 1-5<br>* Other names: Enbrel;Drug: Rituximab<br>* (375 mg/m2) Using Stepped-Up Dosing Thrice Weekly, weeks 2-5<br>* Other names: RITUXAN®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the feasibility and toxicity of the combination of etanercept and rituximab in patients with CLL/SLL. |  | up to 1 year | 
| Determine if etanercept increases the complete response rate while decreasing the frequency of infusion-related toxicity in patients with CLL/SLL receiving rituximab therapy. |  | up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Leukemia, Lymphoma