Safety & Efficacy Study of Perifosine + Bortezomib +/- Dexamethasone for Multiple Myeloma Patients

Inclusion Criteria:

1. Subject was previously diagnosed with multiple myeloma based on standard diagnostic criteria, as follows.

   Major criteria:
   * Plasmacytomas on tissue biopsy.
   * Bone marrow plasmacytosis (\> 30% plasma cells).
   * 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:
   * Bone marrow plasmacytosis (10 to 30% plasma cells).
   * Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria.
   * Lytic bone lesions.
   * Normal IgM \< 50 mg/dL, IgA \< 100 mg/dL or IgG \< 600 mg/dL.
2. Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:
3. Any two of the major criteria.
4. Major criterion 1 plus minor criterion b, c, or d.
5. Major criterion 3 plus minor criterion a or c.
6. Minor criteria a, b, and c or a, b, and d.
7. Patients must have relapsed or refractory disease (refractory is defined as progression during treatment or within 60 days after the completion of treatment).
8. Patients must have been previously treated with bortezomib. Patients may have received prior perifosine.
9. Age \>= 18 years at the time of signing informed consent document.
10. All necessary baseline studies for determining eligibility must be obtained within 14 days prior to enrollment. (Pregnancy test must be within 7 days for women of childbearing potential.)
11. Subject has an ECOG (Zubrod) performance status of 0 to 2.
12. Subject must be able to adhere to the study visit schedule and other protocol requirements.
13. Subject must understand and voluntarily sign an informed consent document.
14. Women of child-bearing potential (WCBP)- must have a negative serum or urine pregnancy test within 72 hours prior to enrollment. In addition, all sexually active WCBP and male patients must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study.

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 (ULN) and/or patients with bilirubin \>= 1.5 X ULN.
3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine).
4. Concomitant medications that include corticosteroids (except as indicated for other medical conditions or up to 100 mgs of hydrocortisone or equivalent as premedication for administration of certain medications or blood products), chemotherapy, or other therapy that is or may be active against myeloma within 2 weeks prior to Cycle 1 Day 1. Nitrosoureas must be discontinued 6 weeks prior to Cycle 1 Day 1.
5. Subjects with hemoglobin \< 8.0 g/dL.
6. Subjects with an absolute neutrophil count (ANC) \<= 500 cells/mm3.
7. Peripheral neuropathy of grade 3 or greater. Patients with painful grade 2 neuropathy are also excluded.
8. Subjects with evidence of mucosal or internal bleeding and/or platelet refractory (i.e., unable to maintain a platelet count \>= 50,000 cells/mm3).
9. Previous history of intolerance of bortezomib or perifosine.
10. 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.
11. WCBP who are pregnant or breast-feeding or men and women who are not using adequate contraception.
12. Plasma cell leukemia at time of study entry.