Chronic Lymphocytic Leukemia - The Leukemia & Lymphoma Society

Kinase Inhibitor Therapy. Kinases are enzymes that are found in both normal
cells and cancer cells. Some cancer cells can be targeted by kinase inhibitor drugs
that destroy the cancer cells. Kinase inhibitor drugs may be associated with fewer
side effects than some other chemotherapy agents. There are many different
kinases in CLL cells, including a phosphatidylinositol 3-kinase (PI3-kinase) and
Bruton’s tyrosine kinase (BTK).
Examples of kinase inhibitor therapy include
{ { PCI-32765. PCI-32765 is an orally administered BTK inhibitor that is in
phase II clinical trials for CLL where significant durable remissions have
been observed with single agent activity and it has shown a very favorable
side-effect profile. Efforts to combine PCI-32765 with other agents such as
bendamustine (Treanda®) or ofatumumab (Arzerra®) are ongoing. Phase III
studies are being planned for this agent. This agent does cause temporary
lymphocytosis (high lymphocyte count) when given by itself but this has not
been shown to have any significant clinical consequence.
{ { CAL-101. CAL-101 is an orally administered PI3-kinase inhibitor that is in
phase II clinical trials for CLL where significant durable remissions have been
observed with single agent activity. Efforts to combine CAL-101 with other
agents such as Treanda, rituximab (Rituxan®), or Arzerra are ongoing. Phase
III studies are being planned for this agent. This agent also causes temporary
lymphocytosis (high lymphocyte count) when given by itself but this has not
been shown to have any significant clinical consequence.
{ { Flavopiridol. Flavopiridol is a CDK inhibitor being studied in people with
high-risk genetic features whose CLL has responded to few, if any, standard
treatments. It is being studied to treat CLL or prolymphocytic leukemia
arising from CLL that is refractory to fludarabine.
{ { Dinaciclib. Dinaciclib is a second-generation CDK inhibitor being studied
in patients with relapsed CLL who are not responsive to other therapies. It
has shown activity in this group including patients with high-risk genetic
features.
Monoclonal Antibody. Xm5574 is an antibody that targets CD19 on the
surface of CLL cells. It is being studied in phase I/II clinical trials in CLL.
Immunomodulatory Drug. Lenalidomide (Revlimid®) is an oral drug that
is used to treat patients with myeloma. It stimulates a person’s own immune
system to attack cancer cells. This drug is being evaluated in several CLL trials,
including a phase III study, to determine if Revlimid, given as a maintenance
therapy, is safe and effective in further improving the quality and duration of
the response to treatment. This study will compare the effects of Revlimid with
the effects of a placebo. Revlimid is also being studied as a possible treatment for
people with CLL following second-line therapy. Other studies include Revlimid
with Rituxan or Arzerra; Revlimid, fludarabine and Rituxan combined for
minimally treated and untreated CLL patients; and Revlimid, fludarabine and
cyclophosphamide combined for patients with advanced-relapsed or refractory
Chronic Lymphocytic Leukemia I page 21