This is a phase 2 study of perifosine in patients with multiple myeloma. Patients will receive perifosine 150 mg at bedtime (qhs) daily. Patients will be assessed by serum and/or urine-electrophoresis at least every 3 weeks.

Treatment: Patients will take three 50 mg tablets of perifosine qhs daily with food. All patients should continue therapy unless disease progression is documented on two occasions at least 1 week apart. Progressing patients will have dexamethasone 20 mg twice per week added to the perifosine. Patients who experience toxicity may continue on treatment with doses delayed or reduced.

Evaluations: Serum and/or urine-electrophoresis will be evaluated for progression or response at 3 week intervals.

This study will enroll a total of up to 64 patients.

Inclusion Criteria:

Major criteria:

1. Plasmacytomas on tissue biopsy.
2. Bone marrow plasmacytosis (> 30% plasma cells).
3. Monoclonal immunoglobulin spike on serum electrophoresis immunoglobulin G (IgG) > 3.5 g/dL or immunoglobulin A (IgA) > 2.0 g/dL; kappa or lambda light chain excretion > 1 g/day on 24 hour urine protein electrophoresis.

Minor criteria:

1. Bone marrow plasmacytosis (10 to 30% plasma cells)
2. Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria
3. Lytic bone lesions
4. Normal immunoglobulin M (IgM) < 50 mg/dL, IgA < 100 mg/dL or IgG < 600 mg/dL.

Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:

1. Any two of the major criteria.
2. Major criterion 1 plus minor criterion b, c or d.
3. Major criterion 3 plus minor criterion a or c.
4. Minor criteria a, b and c or a, b and d.

Exclusion Criteria:

1. Renal insufficiency (serum creatinine levels > 3 mg/dL).
2. Patients who present with either ALT or AST ≥ 2.5 X upper limit of normal.
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine).
4. Concomitant therapy medications that include corticosteroids (except as indicated for other medical conditions, or up to 100 mgs of hydrocortisone as premedication for administration of certain medications or blood products) or other chemotherapy that is or may be active against myeloma, or therapy with chemotherapy within 3 weeks prior to Day 1. Nitrosoureas must be discontinued 6 weeks prior to Day 1.
5. Subjects with a hemoglobin < 8.0 g/dL.
6. Any condition, including laboratory abnormalities, that in the opinion of the Investigator, places the subject at unacceptable risk if he/she were to participate in the study.
7. Women of childbearing potential (WCBP) who are pregnant, or breast-feeding or men and women who are not using adequate contraception are excluded.
8. Plasma cell leukemia.