Assessment of Efficacy and Safety of Perifosine, Bortezomib and Dexamethasone in Multiple Myeloma Patients

• Overall survival [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
• Overall response rate [ Time Frame: 6 - 24 months ] [ Designated as safety issue: No ]
• Adverse Events [ Time Frame: Up to 24 months ] [ Designated as safety issue: Yes ]

• Overall survival [ Time Frame: q 3 weeks ] [ Designated as safety issue: Yes ]
• Overall response rate [ Time Frame: q 3 weeks ] [ Designated as safety issue: Yes ]
• Adverse Events [ Time Frame: q 3 weeks ] [ Designated as safety issue: Yes ]

This is a randomized Phase III study to evaluate the efficacy and safety of perifosine when added to the combination of bortezomib and dexamethasone in multiple myeloma patients who have relapsed on a prior bortezomib treatment regimen.

A pre-planned interim analysis is expected to take place in Q1 of 2013.

• Drug: Perifosine
  Perifosine will be dosed as one 50 mg pill every day of each cycle.
• Drug: Perifosine Placebo
  Perifosine placebo will be dosed as one 50 mg pill every day of each cycle.
• Drug: Bortezomib
  Bortezomib will be dosed at 1.3 mg/m2 on Days 1, 4, 8, and 11 every 21 days.
• Drug: Dexamethasone
  Dexamethasone will be administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.

• Experimental: Perifosine + Bortezomib + Dexamethasone
  Interventions:

  • Drug: Perifosine
  • Drug: Bortezomib
  • Drug: Dexamethasone
• Placebo Comparator: Placebo + Bortezomib + Dexamethasone
  Interventions:

  • Drug: Perifosine Placebo
  • Drug: Bortezomib
  • Drug: Dexamethasone

Inclusion Criteria:

• Patient was previously diagnosed with multiple myeloma based on standard diagnostic criteria.
• Patients must have relapsed (progressed > 60 days) after their last dose of bortezomib-based therapy. In addition, patients may be relapsed or refractory to other non-bortezomib-based therapies.
• Patient has received at least 1 but not more than 4 prior anti-myeloma regimens and has progressive disease after the most recent treatment regimen.
• Patients must have adequate organ and marrow function.

Exclusion Criteria:

• Patients must not be refractory to any bortezomib-containing regimen.
• History of allergic reactions or intolerance attributed to compounds of similar chemical or biologic composition to perifosine (miltefosine or edelfosine), bortezomib or dexamethasone or any of their components.
• Prior treatment with perifosine or an investigational proteasome inhibitor.
• Chemotherapy or other therapy experimental or proven that is or may be active against myeloma within two weeks (14 days) prior to Cycle 1 Day 1.