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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

Use of Valproic Acid in Relapsed or Refractory Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00810680
• Other study ID #: IRCH-VAL-01
• Status: Recruiting
• Phase: N/A
• First received: October 21, 2008
• Last updated: December 17, 2008
• Start date: September 2008
• Est. completion date: March 2009

Study information

• Verified date: December 2008
• Source: All India Institute of Medical Sciences, New Delhi
• Contact: Vinod Raina, MD, FRCP
• Phone: 91-11-2659 3679
• Email: vinodraina[@]hotmail.com
• Is FDA regulated: No
• Health authority: India: Drugs Controller General of India
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: March 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

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.

Locations

Country	Name	City	State
India	Institute Rotary Cancer Hospital, All India Institute of Medical Sciences	New Delhi	Delhi

Sponsors (1)

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

Country where clinical trial is conducted

India, 

References & Publications (1)

Bokelmann I, Mahlknecht U. Valproic acid sensitizes chronic lymphocytic leukemia cells to apoptosis and restores the balance between pro- and antiapoptotic proteins. Mol Med. 2008 Jan-Feb;14(1-2):20-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Best clinical response as defined by NCIWG criteria for CLL		3 months	No
Secondary	Hematological toxicity (graded according to NCIWG criteria for CLL)		3 months	Yes
Secondary	Non- hematological toxicity (graded according to NCI common toxicity criteria)		3 months	Yes