A Study of Imatinib and Valproic Acid in Patients With Chronic Myelogenous Leukemia (CML)

Study Overview
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Brief Summary
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The aim of this study is to test the effect of the combination of valproate in combination with imatinib with an aim of achieving a maximal molecular response as the primary goal.

Detailed Description
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The aim of this study is to test the effect of the combination of valproate in combination with imatinib with an aim of achieving a maximal molecular response as the primary goal. Briefly, patients with CML who are taking imatinib and have been found to have a plateau in their level of the bcr-abl transcript will be eligible to participate in the study. Valproate will then be added to the imatinib, and subsequent bcr-abl transcripts will be monitored to see if the addition of valproate produced a further reduction. Patients will be monitored for efficacy and toxicity.

Official Title
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A Phase II Study of Imatinib and Valproic Acid in Patients With CML

Conditions
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Chronic Myelogenous Leukemia

Intervention / Treatment
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* Drug: Gleevec (imatinib), valproic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients, 18 years of age or older, with a diagnosis of CML. Patients must have a life expectancy of at least 12 weeks. Patients must have an ECOG performance status of 0-2. Patients must sign an informed consent. Patients should have adequate hepatic function with a total bilirubin < 2 mg/dl and SGOT or SGPT < two times the upper limit of normal, and adequate renal function as defined by a serum creatinine < 1.5 x upper limit of normal. Patients with CML in chronic phase on imatinib as first line therapy who fulfill the following criteria: The patient has at least two tests for quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for bcr-abl (peripheral blood or bone marrow aspirate). The results of these tests should demonstrate a relative plateau in the effect of imatinib on the detected level of the transcript (i.e. there should less than a ½ log difference between the last two values). Note: Patients will be eligible if the more recent study is greater than the previous study by any value. The last two quantitative RT-PCR studies should be at least 3 months apart. The patient should have received at least 9 months of imatinib since the diagnosis of CML. The patient is tolerating imatinib without any grade 3 or greater toxicity. Exclusion Criteria: Pregnant women or nursing mothers are not eligible for this trial. Patients of child bearing potential must use adequate contraception. Patients may receive no other concurrent chemotherapy or radiation therapy during this trial. Patients with severe medical problems such as uncontrolled diabetes mellitus or cardiovascular disease or active infections are not eligible for this trial. Patients who have a hypersensitivity to valproic acid, derivatives, or any component of the formulation. Patients with hepatic disease or significant impairment, or urea cycle disorders

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

| Intervention/Treatment |
| --- |
|Drug: Gleevec (imatinib), valproic acid|Valproic acid: 250 mg three times per day and then adjusted according to attain a therapeutic level. Gleevec will be continued at the dose the patient was taking at the time of entry onto the study.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure the effect of the combination of valproate in combination with imatinib with an aim of achieving a maximal molecular response as the primary goal. |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CML, Chronic Myelogenous leukemia, INST 0901, imatinib, valproic acid, Gleevec