Perifosine in Patients With Relapsed/Refractory Waldenstrom's Macroglobulinemia

Perifosine is a drug that in particular inhibits Akt thought to be important for initiation
and progression of malignancies, specifically in lymphomas. In laboratory experiments of WM
and lymphoma cell lines, perifosine has shown to have cytotoxic and anti-proliferative
activity as a single agent. This drug has been used in clinical research studies of other
types of cancers including soft tissue sarcomas, head and neck cancers and prostate cancer.
This study uses a two-stage design to evaluate efficacy of perifosine based on overall
response (OR). The null and alternative OR rates are 20% and 40%. If 4 or more patients
enrolled in the stage one cohort (n=17 patients) achieve OR than accrual will proceed to
stage two (n=20 patients). If fewer than 10 ORs are observed then the regimen will be
considered ineffective.

Inclusion Criteria:

- 18 years of age or older

- Must have received prior therapy for their WM and have relapsed or refractory WM. Any
number of prior therapies is acceptable

- Measurable disease, defined as presence of immunoglobulin M paraprotein with a minimum
IgM level of equal to or greater than 2 times the ULN and over 10% of
lymphoplasmacytic cells in bone marrow

- ECOG Performance Status 0,1, or 2

- Laboratory values as described in the protocol

- Life expectancy of greater than 12 weeks

Exclusion Criteria:

- Uncontrolled infection

- Other active malignancies

- CNS involvement

- Cytotoxic chemotherapy less than 3 weeks, or biologic therapy less than 2 weeks, or
corticosteroids less than 2 weeks prior to registration.

- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy
considered investigational

- Pregnant or nursing women

- Known to be HIV positive

- Radiation therapy less than 2 weeks prior to registration