Pretreatment With Valproate Prior to Immunotherapy Targeting Cluster of Differentiation Antigen 20 in Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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This trial includes patients with chronic lymphocytic leukemia, the most common kind of malignant lymphoma. Monoclonal antibodies directed against cluster of differentiation antigen 20 have improved treatment results in different forms of lymphomas; however in chronic lymphocytic leukemia treatment with monoclonal antibodies is less effective, and it has been suggested that this is depending on a lower expression of the cluster of differentiation antigen 20 protein on the chronic lymphocytic leukemia cells. Valproate, an anticonvulsant drug, has been shown to increase the cluster of differentiation antigen 20 expression, and the rationale in this study is that an increasement of cluster of differentiation antigen 20 would make treatment with monoclonal antibodies in patients with chronic lymphocytic leukemia more effective.

Official Title
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Pretreatment With Valproate Prior to Immunotherapy Targeting Cluster of Differentiation Antigen 20 in Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Valproate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years Histologically confirmed chronic lymphocytic leukemia Leucocyte count more than 20 x 10 9/L No other simultaneous treatment for lymphoma No treatment indicated for chronic lymphocytic leukemia WHO performance status 0-2 HIV negativity Negativity for hepatitis C virus , HBsAG, anti-hepatitis B core antigen, or other active infection uncontrolled by treatment Agree to abstain from donating blood while taking study drug therapy and for one week following discontinuation of study drug therapy Agree not to share study medication with another person and to return all unused study drug to the investigator Written informed concent Exclusion Criteria: Psychiatric illness or condition which could interfere with the subjects' ability to understand the requirements of the study Neurological or neuropsychiatric disorder, interfering with the requirements of the study Hearing impairment over grade 2 Porphyria History of acute or chronic hepatitis Family history of severe drug-induced hepatitis Pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Valproate<br> | Drug: Valproate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of CD20 protein and messengerRNA in response to treatment with valproate in patients with chronic lymphatic leukemia. |  | Blood samples to determine the level of CD20 and messengerRNA are taken day 1 and 4 at each cycle; 3 cycles are given with a cycle length of 21 days. Valproate concentration are taken day 1, 2, 3 and 4 at each cycle. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Translational blood samples. |  | Blood tests for translational studies of the epigenetic and transcriptional regulation of the CD20 promotor are taken prestudy, day 1, 2, 3 and 4 at each cycle and 3 months post treatment. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Valproate, Chronic Lymphocytic Leukemia, Cluster of differentiation antigen 20, Lymphomas, B-cell lymphomas, Translational research, Monoclonal antibodies