A Study of Bortezomib and Pegylated Liposomal Doxorubicin in Patients With Relapsed Multiple Myeloma Previously Treated With Bortezomib
A Study of Bortezomib and Pegylated Liposomal Doxorubicin in Patients With Relapsed Multiple Myeloma Previously Treated With Bortezomib
The purpose of this study is to evaluate the safety and effectiveness of using pegylated
 liposomal doxorubicin and bortezomib in the treatment of patients with relapsed multiple
 myeloma who had been previously treated with bortezomib. Multiple myeloma is a cancer that
 begins in plasma cells, a type of white blood cell. These cells are part of the immune
 system, which helps protect the body from germs and other harmful substances. In time,
 myeloma cells collect in the bone marrow and in the solid parts of bone. Multiple myeloma
 treatment may include stem cell transplantation, however, not all patients with multiple
 myeloma are candidates for stem cell transplantation and many patients who receive
 transplants relapse. As a result, additional first and later-line therapeutic options are
 needed for patients who are not candidates for transplantation, or whose disease relapses
 after transplantation or other therapies. Pegylated liposomal doxorubicin in combination with
 bortezomib is approved for the treatment of patients with multiple myeloma who have not
 previously received bortezomib and have received at least one prior therapy. The combined use
 of pegylated liposomal doxorubicin and bortezomib in this study is designed to evaluate the
 overall response rate and safety in patients with multiple myeloma who have been previously
 treated with bortezomib.
The primary purpose of this study is to evaluate the overall response rate to DOXIL/VELCADE
 treatment in patients with relapsed multiple myeloma previously treated with VELCADE. Overall
 response rate is defined as the proportion of patients achieving either a complete response
 (CR) or partial response (PR) to treatment according to the European Group for Blood and
 Marrow Transplantation (EBMT) criteria. This is a single arm (all patients will receive the
 same drug combination and dose), multi-center (many study sites), open label (the patient and
 the physician know the drug treatment being received) of approximately 60 patients with
 multiple myeloma whose disease has progressed after initial response to VELCADE-based
 therapy. During each 21-day treatment cycle, patients will receive VELCADE by intravenous
 bolus on 4 designated days, and DOXIL by intravenous infusion on one designated day.
 Treatment will continue until disease progression, or the occurrence of unacceptable
 treatment-related toxicity or up to a total of 8 cycles of therapy. Drug doses may be delayed
 or dropped as needed to allow for platelet transfusions or other treatment requirements.
 Patients responding to treatment at study end may be evaluated for continued treatment for as
 long as treatment can be tolerated and they continue to respond. After discontinuation of all
 study drugs, patients who have not had disease progression will be followed for 6 months
 after receiving the last dose of study drug. The primary endpoint is overall response rate as
 defined by the proportion of patients achieving either a complete response or a partial
 response. Response will be assessed at each cycle. Safety will be monitored throughout the
 study by physical examination, clinical laboratory testing, and the incidence and severity of
 reported adverse events. Overall safety will be summarized at study-end.

 During each 21-day treatment cycle, patients will receive bortezomib 1.3 mg/m2 by intravenous
 bolus on Days 1, 4, 8 and 11 and pegylated liposomal doxorubicin 30 mg/m2 by intravenous
 infusion on Day 4.
Inclusion Criteria:

 -  Confirmed diagnosis of Multiple Myeloma

 -  Received prior courses of bortezomib (VELCADE)-based therapy

 -  Greater than or equal to 50% reduction in M-Protein sustained for a minimum of 60 days
 and no evidence of progression of disease while on the most recent course of
 VELCADE-based therapy

 -  60 days or more since the patient's last VELCADE dose

 -  Life expectancy > 3 months

 -  Progressive disease defined by new or worsening lytic bone lesions or plasmacytoma or
 hypercalcemia or a >25% increase in M-protein

 Exclusion Criteria:

 -  No patients with progressive disease while receiving an anthracycline-based regimen

 -  No patients with >2 prior regimens for the treatment of multiple myeloma

 -  No major surgery within 2 weeks before screening

 -  No patients with history of allergic reaction to compounds containing boron, mannitol,
 anthracycline, or liposomal formulations of any agent

 -  No patients known to be human immunodeficiency virus (HIV) positive

 -  No patients with poorly controlled hypertension, diabetes mellitus, or other serious
 medical or psychiatric illness

 -  No patients with an active systemic infection requiring treatment