Maximum tolerated dose was the dose that was 1 step lower than the dose where at least one third of patients experienced DLT. A DLT was defined as any of the following occurring during the first cycle:

• grade 4 hematologic toxicity without regard for relationship to study drug treatment
• thrombocytopenia grade 3 with grade 3 or grade 4 hemorrhage
• grade 3 febrile neutropenia
• grade 3 or grade 4 nausea and vomiting refractory to anti emetic therapy
• any study drug related grade 3 or grade 4 nonhematologic toxicity
• any drug related death

Toxicity grades (3=severe AE and 4=life-threatening or disabling AE) were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.

Safety population

Overall tumor response is the sum of a complete response (CR), very good partial response (VGPR), partial response (PR) and minimal response (MR). A modified version of the Bladé criteria for response was used. Abbreviated definitions for the response categories can be found in the description of outcome #3.

Efficacy population

Abbreviated criteria for response categories: CR includes the disappearance of the original monoclonal protein (M-protein) from blood and urine, and <5% plasma cells in the bone marrow, and no increase in size/number of lytic bone lesions, and disappearance of soft tissue plasmacytomas for >=4 weeks. VGPR includes serum and urine M-protein detectable by immunofixation but not electrophoresis, and reduction in 24-hr urinary light chain excretion by <100 mg, and disappearance of soft tissue plasmacytomas for >= 4 weeks, and no increase in size/number of lytic bone lesions. PR includes a >=50% reduction in serum M-protein, and reduction in 24-hr urinary light chain excretion by either >=90% or to <200 mg, and >=50% reduction in size of soft tissue plasmacytomas, and no increase in size/number of lytic bone lesions. MR includes a >=25% and <=49% reduction in serum M-protein. SD does not meet criteria for the other response categories. See outcome #4 for a definition of PD.

Efficacy population

Time to progression was defined as the time from initiation of therapy to progressive disease (PD). PD requires at least one of the following:

• >25% increase in serum monoclonal paraprotein (which must also be an absolute increase of at least 5 g/L),
• >25% increase in 24-hour urinary light chain excretion (which must also be an absolute increase of at least 200 mg/24 h),
• >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy (which must also be an absolute increase of at least 10%),
• definite increase in the size of existing lytic bone lesions or soft tissue plasmacytomas,
• the development of new bone lesions or soft tissue plasmacytomas,
• the development of hypercalcemia (corrected serum calcium > 11.5 mg/dL or 2.8 mmol/L not attributable to any other cause).

Safety population

Progression free survival is the time between the date of initiation of therapy to progressive disease (PD) or death from any cause, whichever occurs first. See outcome #4 for a definition of PD.

Safety population

Time to first response is defined as the time from the initiation of therapy to the first evidence of a confirmed response (ie, CR, VGPR, PR, or MR).

Participants who had a response

Duration of response (DR) is defined as the time from the first response to progressive disease (PD). See outcome #4 for a PD definition.

Participants who had a response

Overall survival is defined as the time from initiation of therapy to death from any cause or last follow-up visit.

Safety population

Counts of participants who had AEs are summarized in a variety of categories. Severity and relatedness to study drug are in the opinion of the investigator according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0. Severity is rated on a 5-point scale: 1=mild, 2=moderate, 3=severe, 4=life threatening or disabling, and 5= death related to AE. Relatedness is assessed on a 5-point scale: not related, unlikely, possible, probable and definite. Definite, probable and possible answers are reported as 'related' to study medication. Deaths are reported up to 18 months. All the deaths occurred beyond the treatment-emergent timeframe since they occurred 6.5-16 months after the final dosing. All other parts of the summary represent the treatment-emergent timeframe (up to 8.5 months) which is the treatment period plus 30 days.

Safety population