Combination Plerixafor (AMD3100)and Bortezomib in Relapsed or Relapsed/Refractory Multiple Myeloma

The MTD plerixafor in combination with bortezomib is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as highest dose level at which fewer than one-third of patients experience a DLT. The MTD was reached at dose level 5B. The maximum tolerated dose of bortezomib was given on days 3, 6, 10, 13 of 21 each cycle.

Time frame: Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.

Population: All Phase I participants who received at least one dose of the study drug were evaluable for MTD.

A DLT was defined as (a) grade 3 or greater non-hematologic toxicity, considered by the investigator to be related to plerixafor or bortezomib, with the exception of nausea, vomiting or diarrhea unless receiving maximal medical therapy, (b) grade 4 hematologic toxicity defined as: thrombocytopenia with platelets \<10,000 on more than one occasion within first cycle despite transfusion. Grade 4 neutropenia must occur for more than 5 days and/or result in neutropenic fever with elevated temperature (defined as \> 101 degrees F). (c) inability to receive Day 1 dose for Cycle 2 due to toxicity. All adverse events were graded according to the CTEP Common Toxicity Criteria (CTCAE v.3.0).

Time frame: Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.

Population: All Phase I participants who received at least one dose of the study drug were evaluable for DLT.

The MTD plerixafor in combination with bortezomib is determined by the number of patients who experience a dose limiting toxicity (DLT). See subsequent primary outcome measure for the DLT definition. The MTD is defined as highest dose level at which fewer than one-third of patients experience a DLT. The MTD was reached at dose level 5B. The maximum tolerated dose of plerixafor was given on days 1, 2, 3, 6, 10, 13 of 21 each cycle.

Time frame: Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.

Population: All Phase I participants who received at least one dose of the study drug were evaluable for MTD.

Overall response was established based on International Myeloma Working Group (IMWG) criteria with 6 potential categories: Complete Response (CR) which is a complete disappearance of monoclonal paraprotein based on negative immunofixation on the serum M-component and urine M-component and no evidence of myeloma in bone marrow, Very Good Partial Response (VGPR) defined as serum and urine M-component detectable by immunofixation but not on electrophoresis or ≥90% reduction in serum M-component plus urine M-component \<100 mg per 24 hours, Partial Response (PR) ≥50% reduction in serum M-component or ≥90% reduction urine M-component or urine M-component \<200 mg per 24 hours, Minimal Response (MR) ≥25% reduction in serum or urine M-component, Stable Disease (SD) defined as failure to meet any response criteria, and Progressive Disease (PD) ≥ 25% increase from lowest value reported in serum M-component (absolute ≥0.5 g/dL) and/or urine M-component (absolute ≥200 mg/24 hours).

Time frame: Disease was assessed for response every cycle on treatment. The maximum number of cycles received was 25.

Population: All participants with measureable disease at baseline and received at least one dose of the study drug were evaluable for response.

DOR is defined as the time from response to disease progression or death, or date last known progression-free and alive for those who have not progressed or died. DOR was estimated using the Kaplan-Meier method.

Time frame: DIsease was assessed to document response every cycle on treatment and post-treatment every 12 weeks until progression.

Population: All Phase II participants with measureable disease present at baseline and received at least one dose of the study drug were evaluable for DOR.

TTP estimated using the Kaplan-Meier method is defined as the time from registration to progression based on IMWG criteria or date last known progression-free for those who have not progressed. \[Durie BG et al. Leukemia. 2006\] Progression (PD): ≥ 25% increase from lowest value reported in serum M-component (absolute increase ≥0.5 g/dL) and/or urine M-component (absolute increase ≥200 mg/24 hours); if appropriate, a ≥25% increase above the lowest level in the difference between involved and uninvolved FLC levels (absolute increase \>10 mg/dL); If none of these are measurable then ≥25% increase in bone marrow plasma cell percentage above the lowest response level (absolute ≥10%); Definite development of new bone lesions or soft tissue plasmacytomas OR increase in size of existing

Time frame: DIsease was assessed to document progression every cycle on treatment and post-treatment every 12 weeks until progression.

Population: All Phase II participants with measureable disease present at baseline and received at least one dose of the study drug were evaluable for TTP.