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.