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

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.

Study Type: Interventional

Study Design: Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: March 2009

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.

Intervention(s) in this Clinical Trial

• Drug: Valproic acid
  • 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.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Valproic acid

Primary Measures

• Best clinical response as defined by NCIWG criteria for CLL
  • Time Frame: 3 months
    Safety Issue?: No

Secondary Measures

• Hematological toxicity (graded according to NCIWG criteria for CLL)
  • Time Frame: 3 months
    Safety Issue?: Yes
• Non- hematological toxicity (graded according to NCI common toxicity criteria)
  • Time Frame: 3 months
    Safety Issue?: Yes

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.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: All India Institute of Medical Sciences, New Delhi

Overall Clinical Trial Officials and Contacts

Vinod Raina, MD, FRCP Principal Investigator Institute Rotary Cancer Hospital, AIIMS, New delhi, India  

Overall Contact: Vinod Raina, MD, FRCP 91-11-2659 3679 vinodraina@hotmail.com

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00810680

Study ID Number: IRCH-VAL-01

ClinicalTrials.gov Identifier: NCT00810680

Health Authority: India: Drugs Controller General of India