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

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

• Perifosine (Drug), also known as D-21266, KRX-0401: Perifosine will be dosed as one 50 mg pill every day of each cycle.
• Perifosine Placebo (Drug): Perifosine placebo will be dosed as one 50 mg pill every day of each cycle.
• Bortezomib (Drug): Bortezomib will be dosed at 1.3 mg/m2 on Days 1, 4, 8, and 11 every 21 days.
• Dexamethasone (Drug): Dexamethasone will be administered orally at 20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12 of each 21-day cycle.

Primary outcomes

• Determine the PFS (progression free survival) in patients with multiple myeloma, treated with perifosine, bortezomib and dexamethasone compared to patients treated with placebo, bortezomib and dexamethasone [6 - 24 months]: Progression-free survival will be defined as the time between randomization and the date of progression that occurred during the Core Phase.

Secondary outcomes

• Overall survival (OS) [Up to 24 months]: OS is defined as time from randomization to death from any cause during the Core Phase of the study.
• Overall response rate (ORR) [6 - 24 months]: The ORR for each treatment arm will be estimated as the proportion of responders, defined as a patient whose best overall response is PR or better during the treatment period, using criteria prospectively established.
• Adverse Events [Up to 24 months]: Each AE and SAE term submitted will be mapped to a preferred term (PT) using the MedDRA dictionary. The investigator will classify the severity of AEs using the NCI CTCAE v3.0 and will assess the relationship of each event to each study treatment.

Sex: All, ages: 18 Years to any

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.

• Results publication: Richardson PG, Nagler A, Ben-Yehuda D, Badros A, Hari P, Hajek R, Spicka I, Kaya H, Le Blanc R, Yoon SS, Kim K, Martinez-Lopez J, Mittelman M, Shpilberg O, Tothova E, Laubach JP, Ghobria IM, Leiba M, Gatt ME, Sportelli P, Chen M, Anderson KC. Randomized Placebo-Controlled Phase III Study Of Perifosine Combined With Bortezomib and Dexamethasone In Relapsed, Refractory Multiple Myeloma Patients Previously Treated With Bortezomib. Blood 2013 ASH Meeting Proceedings;122:abstract 3189

• Paul Richardson, MD, Principal investigator, Dana-Farber Cancer Institute