Phase I/II Study of Liposomal Doxorubicin (Doxil®)/ Melphalan/Bortezomib (Velcade®) in Relapsed/Refractory Multiple Myeloma
- Determine the safety and tolerability of doxorubicin HCl liposome, melphalan, and
bortezomib in patients with relapsed or refractory stage I-III multiple myeloma.
- Determine the maximum tolerated dose (MTD) of this regimen in these patients.
- Determine the overall response rate, including complete, near-complete, partial, and
minimal response rate, in patients treated with this regimen.
- Determine the time to response, progression-free survival, and overall survival of
patients treated with this regimen.
- Determine the toxic effects of this regimen at the MTD in these patients.
OUTLINE: This is a multicenter, phase I, dose-escalation study followed by a phase II study.
- Phase I: Patients receive doxorubicin HCl liposome IV over 30-60 minutes and melphalan
IV over 30 minutes on day 1 and bortezomib IV on days 1, 4, 8, and 11. Treatment
repeats every 28 days for up to 6 courses in the absence of disease progression or
Cohorts of 3-6 patients receive escalating doses of doxorubicin HCl liposome, melphalan, and
bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the
dose preceding that at which 2 of 3 or 4 of 6 patients experience dose-limiting toxicity
after 2 courses of therapy.
- Phase II: Patients receive doxorubicin HCl liposome, melphalan, and bortezomib at the
MTD as in phase I.
After completion of study treatment, patients are followed every 3 months.
PROJECTED ACCRUAL: Approximately 32 patients will be accrued for this study.
Primary Purpose: Treatment
Proportion of patients experiencing treatment-related ≥ grade 3 hematologic or nonhematologic toxicity or treatment-related death (phase I)
Ajai Chari, MD
Herbert Irving Comprehensive Cancer Center
|UCSF Helen Diller Family Comprehensive Cancer Center||San Francisco, California 94115|
|Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center||New York, New York 10032|