Study of Efficacy and Safety of Valproic Acid in Chronic Lymphocytic Leukemia (CLL)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Valproic acid, as a single agent is effective in the treatment of Chronic Lymphocytic Leukemia which has relapsed or is refractory to therapy with standard drugs.

Detailed Description
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Chronic lymphocytic leukemia (CLL) is a disease characterized by a prolonged clinical course. Though various drugs such as alkylating agents, antimetabolites such as fludarabine and targeted antibodies such as rituximab are effective against this condition, relapses are frequent and cure is rare. There exists a subset of CLL patients who are refractory to many of these first line agents. Though one or the other of the above mentioned class of drugs can be substituted for patients who have relapsed or have refractory disease, no therapy has been conclusively proven to have survival advantage in this condition. The costs and toxicities add to the burden of these therapies. Valproic acid is a well studied drug used for the treatment of epilepsy for over 30 years. It has a well documented side effect profile, is generally well tolerated and is inexpensive. Recently, it has been shown to be an inhibitor of the enzyme, Histone de-acetylase(HDAC). Inhibition of HDAC promotes apoptosis, and could lead to the death of CLL cells which harbor defective apoptotic mechanisms. In vitro studies have proven the ability of therapeutic concentrations of Valproic acid to achieve cell kill in cultures of CLL cells. This study aims to identify whether valproic acid, used in standard doses has single agent activity against CLL and to assess its tolerance in these patients.

Official Title
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Use of Valproic Acid in Relapsed or Refractory Chronic Lymphocytic Leukemia

Conditions
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Chronic Lymphocytic Leukemia

Intervention / Treatment
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* Drug: Valproic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active CLL (as defined by the National Cancer Institute Working Group) Patients must have received at least one prior therapy for CLL and have been treated with a nucleoside analogue. Age 18 years or older. Good general condition as defined by an Eastern cooperative oncology group- performance status (ECOG-PS) </=2. Absolute neutrophil count>1500/cmm and platelet count >30,000/cmm unless the low counts are due to the disease. Adequate liver function (bilirubin<2 mg/dL,ASTorALT <3Xthe upper limit of normal) and renal function (serum creatinine<2 mg/dL or creatinine clearance>30 mL/min) unless abnormalities are as a result of disease involvement. Full recovery from previous treatments. Exclusion Criteria: Any therapy for CLL within 4 weeks before initiating treatment on this study. Pregnancy.

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: Valproic acid<br> | Drug: Valproic acid<br>* Tab. Valproic acid will be started at a dose of 10 mg per kg per day in two or three divided doses. If well tolerated the dose will be increased to a maximum of 20 mg per kg per day and continued for a period of 3 months. The drug will be continued for another 3 months for a maximum of 6 months in responding patients. The drug will be stopped in all those who develop intolerable side effects or develop disease progression during therapy.<br>* Other names: Depakote;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best clinical response as defined by NCIWG criteria for CLL |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematological toxicity (graded according to NCIWG criteria for CLL) |  | 3 months | 
| Non- hematological toxicity (graded according to NCI common toxicity criteria) |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic lymphocytic leukemia, relapsed, refractory, valproic acid, valproate