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Use of Valproic Acid in Relapsed or Refractory Chronic Lymphocytic Leukemia

18 Years
Open (Enrolling)
Chronic Lymphocytic Leukemia

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Trial Information

Use of Valproic Acid in Relapsed or Refractory Chronic Lymphocytic Leukemia

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.

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)
- 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.

Type of Study:


Study Design:

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

Outcome Measure:

Best clinical response as defined by NCIWG criteria for CLL

Outcome Time Frame:

3 months

Safety Issue:


Principal Investigator

Vinod Raina, MD, FRCP

Investigator Role:

Principal Investigator

Investigator Affiliation:

Institute Rotary Cancer Hospital, AIIMS, New delhi, India


India: Drugs Controller General of India

Study ID:




Start Date:

September 2008

Completion Date:

March 2009

Related Keywords:

  • Chronic Lymphocytic Leukemia
  • chronic lymphocytic leukemia
  • relapsed
  • refractory
  • valproic acid
  • valproate
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid