An Open-Label Phase I/II Study of the Safety and Efficacy of Perifosine and Bortezomib With or Without Dexamethasone for Patients With Relapsed or Refractory Multiple Myeloma Previously Treated With Bortezomib
The primary objective of the phase I portion is to determine the maximum tolerated dose of
perifosine in combination with bortezomib in patients previously treated with bortezomib.
All patients will receive daily perifosine qhs with food. In the initial phase I study, 3
patients will be entered into a specified combination of perifosine and bortezomib cohorts.
If no dose-limiting toxicity is observed, then three additional patients will be entered in
cohort 4 - a full dose of bortezomib (1.3 mg/m2 on days 1, 4, 8 and 11 every 3 weeks). If
this dose is tolerated it will be used for the phase II study, otherwise an intermediate
dose of 1 mg/m2 on days 1, 4, 8, and 11 every 3 weeks will be employed.
The phase II study will use the maximum tolerated dose of bortezomib and perifosine. The
primary objective of phase II portion is to determine the response rate (the combined CR +
PR + MR) following treatment with perifosine + bortezomib in patients with multiple myeloma
who have relapsed following initial front-line therapy, are refractory to their most recent
therapy, and were previously treated with bortezomib. The secondary objectives of the
phase II portion are;
1. To further assess the safety and tolerability of perifosine in combination with
bortezomib—with or without dexamethasone—in patients with multiple myeloma.
2. To obtain correlative data in patients with multiple myeloma treated with perifosine in
combination with bortezomib—with or without dexamethasone (NOTE Centers may choose not
to participate in correlative studies).
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I toxicities
Every 3 weeks
Paul Richardson, MD
Dana-Farber Cancer Institute
United States: Food and Drug Administration