Perifosine in Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
| Status: | Archived |
|---|---|
| Conditions: | Blood Cancer, Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | August 2009 |
| End Date: | August 2014 |
Phase II Trial of Perifosine in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Perifosine inhibits the AKT pathway (a way cells communicate with each other). This pathway
is felt to be important in the development of several types of cancers including chronic
lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). It is thought perifosine may
be able to block this pathway and lead to an improvement in the CLL or SLL. The purpose of
this trial is to see if perifosine is an effective treatment for relapsed or refractory CLL
or SLL. Another purpose of this study is to look at the effect perifosine has on cells.
Chronic lymphocytic leukemia and small B-cell lymphocytic lymphoma represent different
manifestations of the same disease. CLL/SLL (hereafter denoted by CLL) is a clonal disorder
of small B lymphocytes expressing a characteristic morphology and immunophenotype. The B
cells express CD19, dim CD 20, dim CD 5, CD 23, CD 43, CD 79a, and weakly express surface
immunoglobin. CLL can present asymptomatically in 25% of patients when diagnosed on a
complete blood count. It also can present with diffuse painless lymphadenopathy and, in a
smaller number of patients, B symptoms.
CLL is characterized by accumulation of circulating B cells predominantly in the G0 phase of
the cell cycle. These cells are resistant to apoptosis. CLL has been found to have aberrant
signaling in several pathways including NF-kB, Akt/PI3K, and JNK/STAT pathways. Akt is
important in promoting CLL survival and viability, as seen in in vitro experiments where
blocking its activity results in apoptosis. Thus an AKT inhibitor may lead to increased
apoptosis and may have a role in the treatment of this disease.
Treatment options for CLL range from a watch and wait approach to high dose chemotherapy
with stem cell support. Currently, there is no consensus on the best treatment regimen,
since no treatment has been shown to improve survival in randomized prospective clinical
trials. New approaches to treatment, especially those with lower toxicity rates, are needed.
Perifosine has been shown to inhibit or otherwise modify signaling through a number of
different signal transduction pathways, including Akt, MAPK, and JNK. These pathways are
involved in the development of cancers and resistance to chemotherapy. Perifosine is of
particular interest, especially due to the difficulty in discovery of drugs that inhibit
these pathways with minimal toxicity. The effect of perifosine on CLL cells has been tested
in the laboratory and has been shown to be an active agent against primary CLL cells in
vitro.
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