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

• Sponsor: Dana-Farber Cancer Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT00903968
• Collaborator: Brigham and Women's Hospital (Other), Genzyme, a Sanofi Company (Industry), Millennium Pharmaceuticals, Inc. (Industry)
• Enrollment: 58
• Locations: 5
• Arms: 9
• Actual Duration (Months): 88
• Patients Per Site: 11.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this research study is to determine the safety of plerixafor and bortezomib, and the highest dose that can be given to people safely. Plerixafor appears to stop myeloma cells from attaching to bone marrow and has been used in other phase I studies for mobilization of stem cells for patients with myeloma and lymphoma. We have shown that the combination of plerixafor and bortezomib is very effective in killing myeloma cells in the laboratory more than the effect of each drug alone.

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Plerixafor; Drug: bortezomib; Drug: Dexamethasone	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 58 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I/II Trial of Combination Plerixafor (AMD3100) and Bortezomib in Relapsed or Relapsed/Refractory Multiple Myeloma
• Actual Study Start Date: Jun 1, 2009
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Oct 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase I Dose Level 1 Phase I Dose Level 1 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Drug: Plerixafor; Other Names: AMD3100 ; Drug: bortezomib; Other Names: velcade
Experimental: Phase I Dose Level 2 Phase I Dose Level 2 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Drug: Plerixafor; Other Names: AMD3100 ; Drug: bortezomib; Other Names: velcade
Experimental: Phase I Dose Level 3 Phase I Dose Level 3 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Drug: Plerixafor; Other Names: AMD3100 ; Drug: bortezomib; Other Names: velcade
Experimental: Phase I Dose Level 4 Phase I Dose Level 4 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Drug: Plerixafor; Other Names: AMD3100 ; Drug: bortezomib; Other Names: velcade
Experimental: Phase I Dose Level 5 Phase I Dose Level 5 patients received plerixafor 320ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Drug: Plerixafor; Other Names: AMD3100 ; Drug: bortezomib; Other Names: velcade
Experimental: Phase I Dose Level 5B Phase I Dose Level 5B patients received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Drug: Plerixafor; Other Names: AMD3100 ; Drug: bortezomib; Other Names: velcade
Experimental: Phase I Dose Level 6 Phase I Dose Level 6 patients received plerixafor 400ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Drug: Plerixafor; Other Names: AMD3100 ; Drug: bortezomib; Other Names: velcade
Experimental: All Phase I Participants All Phase I participants received plerixafor by injection and bortezomib intravenously according to the established dose escalation schedule. Participants were treated until disease progression or unacceptable toxicity.	Drug: Plerixafor; Other Names: AMD3100 ; Drug: bortezomib; Other Names: velcade
Experimental: All Phase II Participants All Phase I participants received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13, bortezomib 1.3 mg/m2 intravenously or subcutaneously days 3, 6, 10, and 13, and dexamethasone 40mg orally days 3, 6, 10, and 13 of each 21 day cycle during induction. In maintenance, participants received plerixafor, bortezomib, and dexamethasone days 1, 8, 15, and 22 of each 35 day cycle. Participants were treated until disease progression or unacceptable toxicity.	Drug: Plerixafor; Other Names: AMD3100 ; Drug: bortezomib; Other Names: velcade ; Drug: Dexamethasone; Other Names: Decadron

Outcome Measures

Primary Outcome Measures

1. Plerixafor Maximum Tolerated Dose (MTD) [Phase I] [Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.]

   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.

2. Bortezomib Maximum Tolerated Dose (MTD) [Phase I] [Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.]

   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.

3. Number of Participants With Dose Limiting Toxicity (DLT) [Phase I] [Participants were assessed every 3 weeks while on study; The observation period for MTD evaluation was the first 21 days of treatment.]

   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).

4. Response Rate of Plerixafor, Bortezomib, and Dexamethasone in Relapsed or Relapsed/ Refractory Multiple Myeloma (ORR) [Phase I and Phase II] [Disease was assessed for response every cycle on treatment. The maximum number of cycles received was 25.]

   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).

Secondary Outcome Measures

1. Time to Progression (TTP) [Phase II] [DIsease was assessed to document progression every cycle on treatment and post-treatment every 12 weeks until progression.]

   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

2. Duration of Response (DOR) [Phase II] [DIsease was assessed to document response every cycle on treatment and post-treatment every 12 weeks until progression.]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 18 years of age or older

• Must have received prior 1-5 therapies for their myeloma and have relapsed or refractory multiple myeloma. Prior therapy with bortezomib is allowed as long as they were not refractory to bortezomib

• Monoclonal protein serum of 1gm/dL or greater or monoclonal light chain in the urine protein electrophoresis of 200 mg/24 hours or greater, or measurable light chains by free light chain assay of 10 mg/dL or greater, or measurable plasmacytoma

• ECOG Performance Status 0, 1, or 2

• Laboratory values as outlined in the protocol

Exclusion Criteria:

• Uncontrolled infection

• Cytotoxic chemotherapy < 3 weeks, or biologic or targeted novel therapy < 2 weeks, or corticosteroids < 2 weeks prior to registration. Patients may be receiving chronic corticosteroids if they are being given for disorders other than myeloma

• Pregnant women

• Nursing women

• Men or women of child-bearing potential who are unwilling to employ adequate contraception

• Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational

• Known to be HIV positive

• Radiation therapy < 2 weeks prior to registration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
2	Cape Cod Hospital	Hyannis	Massachusetts	United States	02601
3	Milford Hospital	Milford	Massachusetts	United States	01757
4	Newton-Wellesley Hospital	Newton	Massachusetts	United States	02462
5	Cancer Treatment Centers of America (Eastern Regional Medical Center)	Philadelphia	Pennsylvania	United States	19124

Sponsors and Collaborators

• Dana-Farber Cancer Institute
• Brigham and Women's Hospital
• Genzyme, a Sanofi Company
• Millennium Pharmaceuticals, Inc.

Investigators

• Principal Investigator: Irene Ghobrial, MD, Dana-Farber Cancer Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Irene Ghobrial, MD, Principal Investigator, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00903968
• Other Study ID Numbers: 08-273
• First Posted: May 19, 2009
• Last Update Posted: Jun 2, 2020
• Last Verified: May 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Irene Ghobrial, MD, Principal Investigator, Dana-Farber Cancer Institute: refractory; relapsed; bortezomib; AMD3100; plerixafor
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Plerixafor; Dexamethasone; Bortezomib

Study Results

Participant Flow

Recruitment Details	Participants in the Phase I study enrolled from June 2009 - July 2011 and the Phase II study from May 2012 - March 2015.

Arm/Group Title	Phase I Dose Level 1	Phase I Dose Level 2	Phase I Dose Level 3	Phase I Dose Level 4	Phase I Dose Level 5	Phase I Dose Level 5B	Phase I Dose Level 6	All Phase II Participants
Arm/Group Description	Phase I Dose Level 1 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 2 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 3 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 4 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 5 patients received plerixafor 320ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 5B patients received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 6 patients received plerixafor 400ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	All Phase II participants received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13, bortezomib 1.3 mg/m2 intravenously or subcutaneously days 3, 6, 10, and 13, and dexamethasone 40mg orally days 3, 6, 10, and 13 of each 21 day cycle during induction. In maintenance, participants received plerixafor, bortezomib, and dexamethasone days 1, 8, 15, and 22 of each 35 day cycle. Participants were treated until disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	3	3	3	3	4	6	3	33
COMPLETED	0	0	0	0	0	0	0	0
NOT COMPLETED	3	3	3	3	4	6	3	33

Baseline Characteristics

Arm/Group Title	All Phase I Particiapnts	All Phase II Participants	Total
Arm/Group Description	All Phase I participants received plerixafor by injection and bortezomib intravenously according to the established dose escalation schedule. Participants were treated until disease progression or unacceptable toxicity.	All Phase II participants received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13, bortezomib 1.3 mg/m2 intravenously or subcutaneously days 3, 6, 10, and 13, and dexamethasone 40mg orally days 3, 6, 10, and 13 of each 21 day cycle during induction. In maintenance, participants received plerixafor, bortezomib, and dexamethasone days 1, 8, 15, and 22 of each 35 day cycle. Participants were treated until disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	25	33	58
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59	63	63
Sex: Female, Male (Count of Participants)
Female	11 44%	9 27.3%	20 34.5%
Male	14 56%	24 72.7%	38 65.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 3%	1 1.7%
Not Hispanic or Latino	25 100%	30 90.9%	55 94.8%
Unknown or Not Reported	0 0%	2 6.1%	2 3.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 3%	1 1.7%
Asian	0 0%	4 12.1%	4 6.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 8%	1 3%	3 5.2%
White	22 88%	27 81.8%	49 84.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 4%	0 0%	1 1.7%
Region of Enrollment (Count of Participants)
United States	25 100%	33 100%	58 100%

Outcome Measures

1. Primary Outcome

Title	Plerixafor Maximum Tolerated Dose (MTD) [Phase I]
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	All Phase I Particiapnts
Arm/Group Description	All Phase I participants received plerixafor by injection and bortezomib intravenously according to the established dose escalation schedule. Participants were treated until disease progression or unacceptable toxicity.
Measure Participants	25
Number [ug/kg]	320

2. Primary Outcome

Title	Bortezomib Maximum Tolerated Dose (MTD) [Phase I]
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	All Phase I Particiapnts
Arm/Group Description	All Phase I participants received plerixafor by injection and bortezomib intravenously according to the established dose escalation schedule. Participants were treated until disease progression or unacceptable toxicity.
Measure Participants	25
Number [mg/m2]	1.3

3. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicity (DLT) [Phase I]
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase I Dose Level 1	Phase I Dose Level 2	Phase I Dose Level 3	Phase I Dose Level 4	Phase I Dose Level 5	Phase I Dose Level 5B	Phase I Dose Level 6
Arm/Group Description	Phase I Dose Level 1 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 2 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 3 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 4 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 5 patients received plerixafor 320ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 5B patients received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 6 patients received plerixafor 400ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.
Measure Participants	3	3	3	3	4	6	3
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	2 NaN

4. Primary Outcome

Title	Response Rate of Plerixafor, Bortezomib, and Dexamethasone in Relapsed or Relapsed/ Refractory Multiple Myeloma (ORR) [Phase I and Phase II]
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Phase I Dose Level 1	Phase I Dose Level 2	Phase I Dose Level 3	Phase I Dose Level 4	Phase I Dose Level 5	Phase I Dose Level 5B	Phase I Dose Level 6	All Phase II Participants
Arm/Group Description	Phase I Dose Level 1 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 2 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 3 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 4 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 5 patients received plerixafor 320ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 5B patients received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	Phase I Dose Level 6 patients received plerixafor 400ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.	All Phase II participants received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13, bortezomib 1.3 mg/m2 intravenously or subcutaneously days 3, 6, 10, and 13, and dexamethasone 40mg orally days 3, 6, 10, and 13 of each 21 day cycle during induction. In maintenance, participants received plerixafor, bortezomib, and dexamethasone days 1, 8, 15, and 22 of each 35 day cycle. Participants were treated until disease progression or unacceptable toxicity.
Measure Participants	3	3	3	3	4	6	3	33
Complete Response	0 0%	0 0%	1 1.7%	0 NaN	0 NaN	0 NaN	0 NaN	1 NaN
Very Good Partial Response	0 0%	0 0%	0 0%	0 NaN	0 NaN	0 NaN	1 NaN	3 NaN
Partial Response	0 0%	0 0%	0 0%	0 NaN	0 NaN	1 NaN	0 NaN	12 NaN
Minimal Response	0 0%	0 0%	0 0%	2 NaN	0 NaN	1 NaN	0 NaN	4 NaN
Stable Disease	3 12%	2 6.1%	2 3.4%	0 NaN	4 NaN	3 NaN	2 NaN	11 NaN
Progressive Disease	0 0%	1 3%	0 0%	1 NaN	0 NaN	1 NaN	0 NaN	2 NaN

5. Secondary Outcome

Title	Time to Progression (TTP) [Phase II]
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	All Phase II Participants
Arm/Group Description	All Phase II participants received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13, bortezomib 1.3 mg/m2 intravenously or subcutaneously days 3, 6, 10, and 13, and dexamethasone 40mg orally days 3, 6, 10, and 13 of each 21 day cycle during induction. In maintenance, participants received plerixafor, bortezomib, and dexamethasone days 1, 8, 15, and 22 of each 35 day cycle. Participants were treated until disease progression or unacceptable toxicity.
Measure Participants	33
Median (95% Confidence Interval) [Months]	12.6

6. Secondary Outcome

Title	Duration of Response (DOR) [Phase II]
Description	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.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	All Phase II Participants
Arm/Group Description	All Phase II participants received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13, bortezomib 1.3 mg/m2 intravenously or subcutaneously days 3, 6, 10, and 13, and dexamethasone 40mg orally days 3, 6, 10, and 13 of each 21 day cycle during induction. In maintenance, participants received plerixafor, bortezomib, and dexamethasone days 1, 8, 15, and 22 of each 35 day cycle. Participants were treated until disease progression or unacceptable toxicity.
Measure Participants	33
Median (95% Confidence Interval) [Months]	12.9

Adverse Events

Time Frame	Assessed each treatment cycle from time of first dose and up to day 30 post treatment.
Adverse Event Reporting Description	Maximum grade toxicity by type was first calculated. Serius AEs were defined as events with plerixafor, bortezomib and/or dexamethasone (phase II only) treatment-attribution of at least possibly and grade 3 or higher per CTCAE v. 3.0. Other AEs were defined as events with plerixafor, bortezomib and/or dexamethasone (phase II only) treatment-attribution of at least possibly and grades 1 or 2 per CTCAE v. 3.0.
Arm/Group Title	Phase I Dose Level 1		Phase I Dose Level 2		Phase I Dose Level 3		Phase I Dose Level 4		Phase I Dose Level 5		Phase I Dose Level 5B		Phase I Dose Level 6		All Phase I Participants		All Phase II Participants
Arm/Group Description	Phase I Dose Level 1 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.		Phase I Dose Level 2 patients received plerixafor 160ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.		Phase I Dose Level 3 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.0 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.		Phase I Dose Level 4 patients received plerixafor 240ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.		Phase I Dose Level 5 patients received plerixafor 320ug/kg by injection on days 1-6 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.		Phase I Dose Level 5B patients received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.		Phase I Dose Level 6 patients received plerixafor 400ug/kg by injection on days 1, 2, 3, 6, 10, and 13 and bortezomib 1.3 mg/m2 intravenously days 3, 6, 10, and 13 of each 21 day cycle until disease progression or unacceptable toxicity.		All Phase I participants received plerixafor by injection and bortezomib intravenously according to the established dose escalation schedule. Participants were treated until disease progression or unacceptable toxicity.		All Phase II participants received plerixafor 320ug/kg by injection on days 1, 2, 3, 6, 10, and 13, bortezomib 1.3 mg/m2 intravenously or subcutaneously days 3, 6, 10, and 13, and dexamethasone 40mg orally days 3, 6, 10, and 13 of each 21 day cycle during induction. In maintenance, participants received plerixafor, bortezomib, and dexamethasone days 1, 8, 15, and 22 of each 35 day cycle. Participants were treated until disease progression or unacceptable toxicity.
All Cause Mortality
	Phase I Dose Level 1		Phase I Dose Level 2		Phase I Dose Level 3		Phase I Dose Level 4		Phase I Dose Level 5		Phase I Dose Level 5B		Phase I Dose Level 6		All Phase I Participants		All Phase II Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Phase I Dose Level 1		Phase I Dose Level 2		Phase I Dose Level 3		Phase I Dose Level 4		Phase I Dose Level 5		Phase I Dose Level 5B		Phase I Dose Level 6		All Phase I Participants		All Phase II Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		2/3 (66.7%)		2/4 (50%)		2/6 (33.3%)		0/3 (0%)		8/25 (32%)		14/33 (42.4%)
Blood and lymphatic system disorders
Anemia	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		1/6 (16.7%)		0/3 (0%)		3/25 (12%)		3/33 (9.1%)
Lymphocytopenia	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		3/25 (12%)		3/33 (9.1%)
Neutropenia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Thrombocytopenia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		8/33 (24.2%)
General disorders
Fatigue	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Infections and infestations
Upper airway infection	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		3/33 (9.1%)
Investigations
Elevated liver function tests	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Metabolism and nutrition disorders
Hyperglycemia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Hyperlipasemia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Hyponatremia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Hypophosphatemia	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		1/6 (16.7%)		0/3 (0%)		2/25 (8%)		0/33 (0%)
Nervous system disorders
Neurologic-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Psychiatric disorders
Insomnia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		2/33 (6.1%)
Renal and urinary disorders
Renal/GU-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Other (Not Including Serious) Adverse Events
	Phase I Dose Level 1		Phase I Dose Level 2		Phase I Dose Level 3		Phase I Dose Level 4		Phase I Dose Level 5		Phase I Dose Level 5B		Phase I Dose Level 6		All Phase I Participants		All Phase II Participants
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		3/3 (100%)		3/3 (100%)		3/3 (100%)		4/4 (100%)		6/6 (100%)		3/3 (100%)		25/25 (100%)		33/33 (100%)
Blood and lymphatic system disorders
Hematologic-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Hemorrhage-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Nose- hemorrhage	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Anemia	3/3 (100%)		2/3 (66.7%)		0/3 (0%)		1/3 (33.3%)		1/4 (25%)		4/6 (66.7%)		0/3 (0%)		11/25 (44%)		13/33 (39.4%)
Leukocytopenia	1/3 (33.3%)		2/3 (66.7%)		0/3 (0%)		0/3 (0%)		2/4 (50%)		0/6 (0%)		1/3 (33.3%)		6/25 (24%)		4/33 (12.1%)
Lymphocytopenia	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		1/6 (16.7%)		1/3 (33.3%)		4/25 (16%)		2/33 (6.1%)
Neutropenia	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/6 (0%)		1/3 (33.3%)		4/25 (16%)		2/33 (6.1%)
Thrombocytopenia	1/3 (33.3%)		3/3 (100%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		3/6 (50%)		1/3 (33.3%)		9/25 (36%)		6/33 (18.2%)
Cardiac disorders
Cardiac-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		3/33 (9.1%)
Ear and labyrinth disorders
Hearing w/o audiogr not in monitor prg	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Middle ear- pain	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Endocrine disorders
Endocrine-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Eye disorders
Double vision	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		1/33 (3%)
Eyelid dysfunction	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		1/33 (3%)
Ocular-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		2/33 (6.1%)
Vision-blurred	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		2/25 (8%)		0/33 (0%)
Eye- pain	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Gastrointestinal disorders
Constipation	2/3 (66.7%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/6 (16.7%)		1/3 (33.3%)		4/25 (16%)		11/33 (33.3%)
Diarrhea	1/3 (33.3%)		1/3 (33.3%)		2/3 (66.7%)		2/3 (66.7%)		4/4 (100%)		4/6 (66.7%)		2/3 (66.7%)		16/25 (64%)		21/33 (63.6%)
Distention/bloating- abdominal	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		2/3 (66.7%)		2/25 (8%)		1/33 (3%)
Dyspepsia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		3/33 (9.1%)
Flatulence	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
GI-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		4/33 (12.1%)
Muco/stomatitis (symptom) oral cavity	0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		2/25 (8%)		0/33 (0%)
Nausea	1/3 (33.3%)		3/3 (100%)		1/3 (33.3%)		2/3 (66.7%)		2/4 (50%)		2/6 (33.3%)		1/3 (33.3%)		12/25 (48%)		11/33 (33.3%)
Obstruction- small bowel NOS	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		2/33 (6.1%)
Ulcer- gastric	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Vomiting	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		1/6 (16.7%)		0/3 (0%)		3/25 (12%)		2/33 (6.1%)
Abdomen- pain	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		1/6 (16.7%)		0/3 (0%)		4/25 (16%)		1/33 (3%)
Anus- pain	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Dental/teeth/peridontal- pain	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
General disorders
Constitutional- other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		3/33 (9.1%)
Fatigue	3/3 (100%)		3/3 (100%)		1/3 (33.3%)		2/3 (66.7%)		4/4 (100%)		5/6 (83.3%)		3/3 (100%)		21/25 (84%)		18/33 (54.5%)
Fever w/o neutropenia	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		3/33 (9.1%)
Rigors/chills	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Sweating	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		1/3 (33.3%)		1/25 (4%)		2/33 (6.1%)
Injection site reaction	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		1/33 (3%)
Taste disturbance	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		2/33 (6.1%)
Edema limb	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		2/3 (66.7%)		2/25 (8%)		4/33 (12.1%)
Pain-other	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		5/33 (15.2%)
Immune system disorders
Allergic reaction	1/3 (33.3%)		0/3 (0%)		2/3 (66.7%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		3/25 (12%)		1/33 (3%)
Allergic rhinitis	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Allergy-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Infections and infestations
Infection Gr0-2 neut- eye NOS	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Infection Gr0-2 neut- lip/perioral	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Infection Gr0-2 neut- middle ear	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Infection Gr0-2 neut- skin	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Infection Gr0-2 neut- upper airway	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		4/33 (12.1%)
Infection w/ gr3-4 neut- colon	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Infection w/ unk ANC sinus	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Infection w/ unk ANC urinary tract NOS	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Infection-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		3/33 (9.1%)
Upper airway infection	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/6 (16.7%)		0/3 (0%)		1/25 (4%)		4/33 (12.1%)
Injury, poisoning and procedural complications
Bruising	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		2/33 (6.1%)
Investigations
Weight gain	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Weight loss	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		1/6 (16.7%)		0/3 (0%)		3/25 (12%)		1/33 (3%)
Alkaline phosphatase	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		3/33 (9.1%)
Bicarbonate	2/3 (66.7%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		3/25 (12%)		2/33 (6.1%)
Bilirubin	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		2/33 (6.1%)
Creatinine	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		2/6 (33.3%)		0/3 (0%)		3/25 (12%)		5/33 (15.2%)
Elevated liver function tests	2/3 (66.7%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		3/25 (12%)		4/33 (12.1%)
Hypercalcemia	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		1/33 (3%)
Hypercholesterolemia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Metabolism and nutrition disorders
Anorexia	2/3 (66.7%)		2/3 (66.7%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		4/25 (16%)		5/33 (15.2%)
Dehydration	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		2/25 (8%)		3/33 (9.1%)
Hyperglycemia	2/3 (66.7%)		2/3 (66.7%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		1/6 (16.7%)		0/3 (0%)		6/25 (24%)		6/33 (18.2%)
Hyperkalemia	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		2/33 (6.1%)
Hypoalbuminemia	2/3 (66.7%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		2/6 (33.3%)		1/3 (33.3%)		6/25 (24%)		8/33 (24.2%)
Hypocalcemia	3/3 (100%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/6 (16.7%)		2/3 (66.7%)		7/25 (28%)		5/33 (15.2%)
Hypoglycemia	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		1/33 (3%)
Hypokalemia	0/3 (0%)		2/3 (66.7%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		1/3 (33.3%)		3/25 (12%)		2/33 (6.1%)
Hypomagnesemia	2/3 (66.7%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		2/25 (8%)		3/33 (9.1%)
Hyponatremia	3/3 (100%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		4/25 (16%)		4/33 (12.1%)
Hypophosphatemia	2/3 (66.7%)		2/3 (66.7%)		2/3 (66.7%)		2/3 (66.7%)		1/4 (25%)		0/6 (0%)		1/3 (33.3%)		10/25 (40%)		5/33 (15.2%)
Metabolic/Laboratory-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		6/33 (18.2%)
Musculoskeletal and connective tissue disorders
Arthritis	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Fracture	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		1/33 (3%)
Musculoskeletal/soft tissue-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		3/33 (9.1%)
Nonneuropathic generalized weakness	1/3 (33.3%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/6 (0%)		1/3 (33.3%)		4/25 (16%)		5/33 (15.2%)
Back- pain	3/3 (100%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		2/4 (50%)		2/6 (33.3%)		0/3 (0%)		7/25 (28%)		10/33 (30.3%)
Bone- pain	1/3 (33.3%)		1/3 (33.3%)		1/3 (33.3%)		1/3 (33.3%)		2/4 (50%)		1/6 (16.7%)		0/3 (0%)		7/25 (28%)		2/33 (6.1%)
Chest wall- pain	3/3 (100%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		3/25 (12%)		1/33 (3%)
Extremity-limb- pain	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		2/25 (8%)		1/33 (3%)
Joint- pain	3/3 (100%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		3/25 (12%)		5/33 (15.2%)
Muscle- pain	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		1/4 (25%)		0/6 (0%)		1/3 (33.3%)		4/25 (16%)		2/33 (6.1%)
Neck- pain	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		2/25 (8%)		1/33 (3%)
Nervous system disorders
Dizziness	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		2/3 (66.7%)		1/4 (25%)		1/6 (16.7%)		0/3 (0%)		5/25 (20%)		4/33 (12.1%)
Neurologic-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		2/33 (6.1%)
Neuropathy CN IV down/in eye move	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Neuropathy CN XII tongue	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Neuropathy, sensory	3/3 (100%)		2/3 (66.7%)		2/3 (66.7%)		1/3 (33.3%)		1/4 (25%)		1/6 (16.7%)		2/3 (66.7%)		12/25 (48%)		19/33 (57.6%)
Neuropathy-motor	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/4 (25%)		2/6 (33.3%)		0/3 (0%)		4/25 (16%)		0/33 (0%)
Tremor	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Head/headache	0/3 (0%)		2/3 (66.7%)		0/3 (0%)		2/3 (66.7%)		1/4 (25%)		1/6 (16.7%)		0/3 (0%)		6/25 (24%)		6/33 (18.2%)
Neuropathic- pain	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Psychiatric disorders
Insomnia	2/3 (66.7%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/4 (25%)		1/6 (16.7%)		2/3 (66.7%)		7/25 (28%)		13/33 (39.4%)
Agitation	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		1/3 (33.3%)		3/25 (12%)		0/33 (0%)
Anxiety	0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		1/3 (33.3%)		4/25 (16%)		3/33 (9.1%)
Confusion	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/6 (16.7%)		0/3 (0%)		2/25 (8%)		0/33 (0%)
Depression	0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		2/33 (6.1%)
Extrapyramidal movement	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		2/3 (66.7%)		2/25 (8%)		0/33 (0%)
Mental status	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/6 (16.7%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Personality	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Psychosis	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		2/3 (66.7%)		2/25 (8%)		0/33 (0%)
Renal and urinary disorders
Incontinence urinary	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		1/6 (16.7%)		0/3 (0%)		1/25 (4%)		1/33 (3%)
Renal/GU-other	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		1/33 (3%)
Urinary frequency/urgency	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		1/33 (3%)
Reproductive system and breast disorders
Testicle- pain	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Respiratory, thoracic and mediastinal disorders
Larynx- pain	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Cough	1/3 (33.3%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		1/4 (25%)		0/6 (0%)		0/3 (0%)		3/25 (12%)		3/33 (9.1%)
Dyspnea	1/3 (33.3%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		2/25 (8%)		6/33 (18.2%)
Skin and subcutaneous tissue disorders
Erythema multiforme	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Induration/fibrosis	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)
Pruritus/itching	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		2/25 (8%)		1/33 (3%)
Rash/desquamation	2/3 (66.7%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		2/4 (50%)		1/6 (16.7%)		0/3 (0%)		6/25 (24%)		1/33 (3%)
Rash: acne/acneiform	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		2/33 (6.1%)
Surgical and medical procedures
Intra-op injury Other (Specify)	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		1/33 (3%)
Vascular disorders
Hypertension	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		3/33 (9.1%)
Hypotension	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		0/25 (0%)		2/33 (6.1%)
Hot flashes	0/3 (0%)		0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		1/33 (3%)
Edema head and neck	0/3 (0%)		0/3 (0%)		1/3 (33.3%)		0/3 (0%)		0/4 (0%)		0/6 (0%)		0/3 (0%)		1/25 (4%)		0/33 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.