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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00810680
Recruitment Status : Unknown
Verified December 2008 by All India Institute of Medical Sciences, New Delhi.
Recruitment status was:  Recruiting
First Posted : December 18, 2008
Last Update Posted : December 18, 2008
Information provided by:
All India Institute of Medical Sciences, New Delhi

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Drug: Valproic acid Not Applicable

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Use of Valproic Acid in Relapsed or Refractory Chronic Lymphocytic Leukemia
Study Start Date : September 2008
Estimated Primary Completion Date : March 2009
Estimated Study Completion Date : March 2009

Arm Intervention/treatment
Experimental: Valproic acid 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.
Other Names:
  • Valproate
  • Sodium Valproate
  • Depakote

Primary Outcome Measures :
  1. Best clinical response as defined by NCIWG criteria for CLL [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. Hematological toxicity (graded according to NCIWG criteria for CLL) [ Time Frame: 3 months ]
  2. Non- hematological toxicity (graded according to NCI common toxicity criteria) [ Time Frame: 3 months ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00810680

Contact: Vinod Raina, MD, FRCP 91-11-2659 3679 ext 3659
Contact: Prasanth Ganesan, MD 91-99681-47800

Institute Rotary Cancer Hospital, All India Institute of Medical Sciences Recruiting
New Delhi, Delhi, India, 110029
Contact: Vinod Raina, MD, FRCP    91- 11- 2659 3679   
Contact: Prasanth Ganesan, MD    91-99681-47800   
Principal Investigator: Vinod Raina, MD, FRCP         
Sub-Investigator: Prasanth Ganesan, MD         
Sponsors and Collaborators
All India Institute of Medical Sciences, New Delhi
Principal Investigator: Vinod Raina, MD, FRCP Institute Rotary Cancer Hospital, AIIMS, New delhi, India

Responsible Party: Dr. Vinod Raina, Institute Rotary Cancer Hospital, AIIMS Identifier: NCT00810680     History of Changes
Other Study ID Numbers: IRCH-VAL-01
First Posted: December 18, 2008    Key Record Dates
Last Update Posted: December 18, 2008
Last Verified: December 2008

Keywords provided by All India Institute of Medical Sciences, New Delhi:
chronic lymphocytic leukemia
valproic acid

Additional relevant MeSH terms:
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Valproic Acid
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs