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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2008 by All India Institute of Medical Sciences, New Delhi.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
All India Institute of Medical Sciences, New Delhi
ClinicalTrials.gov Identifier:
NCT00810680
First received: October 21, 2008
Last updated: December 17, 2008
Last verified: December 2008
  Purpose

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 Intervention
Chronic Lymphocytic Leukemia
Drug: Valproic acid

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Use of Valproic Acid in Relapsed or Refractory Chronic Lymphocytic Leukemia

Resource links provided by NLM:


Further study details as provided by All India Institute of Medical Sciences, New Delhi:

Primary Outcome Measures:
  • Best clinical response as defined by NCIWG criteria for CLL [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Hematological toxicity (graded according to NCIWG criteria for CLL) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Non- hematological toxicity (graded according to NCI common toxicity criteria) [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 10
Study Start Date: September 2008
Estimated Study Completion Date: March 2009
Estimated Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00810680

Contacts
Contact: Vinod Raina, MD, FRCP 91-11-2659 3679 ext 3659 vinodraina@hotmail.com
Contact: Prasanth Ganesan, MD 91-99681-47800 pg1980@gmail.com

Locations
India
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    vinodraina@hotmail.com   
Contact: Prasanth Ganesan, MD    91-99681-47800    pg1980@gmail.com   
Principal Investigator: Vinod Raina, MD, FRCP         
Sub-Investigator: Prasanth Ganesan, MD         
Sponsors and Collaborators
All India Institute of Medical Sciences, New Delhi
Investigators
Principal Investigator: Vinod Raina, MD, FRCP Institute Rotary Cancer Hospital, AIIMS, New delhi, India
  More Information

Publications:
Responsible Party: Dr. Vinod Raina, Institute Rotary Cancer Hospital, AIIMS
ClinicalTrials.gov Identifier: NCT00810680     History of Changes
Other Study ID Numbers: IRCH-VAL-01
Study First Received: October 21, 2008
Last Updated: December 17, 2008
Health Authority: India: Drugs Controller General of India

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

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Valproic Acid
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
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

ClinicalTrials.gov processed this record on July 23, 2014