Carfilzomib, Pegylated Liposomal Doxorubicin Hydrochloride, and Dexamethasone in Treating Patients With Relapsed or Refractory Multiple Myeloma

• Sponsor: Washington University School of Medicine (Other)
• Overall Status: Completed
• CT.gov ID: NCT01246063
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 6
• Actual Duration (Months): 70.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The aim of this phase I/II trial is to determine the maximal tolerated dose (MTD) of carfilzomib together with pegylated liposomal doxorubicin hydrochloride (PLD) with or without dexamethasone, and then to establish the efficacy and safety of this novel combination in patients with relapsed or refractory multiple myeloma

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: carfilzomib; Drug: pegylated liposomal doxorubicin (PLD); Drug: Dexamethasone	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Trial of Carfilzomib, Pegylated Liposomal Doxorubicin, and Dexamethasone for the Treatment of Relapsed/Refractory Multiple Myeloma
• Actual Study Start Date: May 14, 2012
• Actual Primary Completion Date: Dec 28, 2017
• Actual Study Completion Date: Mar 23, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2) Dose Level 0: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Drug: carfilzomib; Other Names: Kyprolis CFZ ; Drug: pegylated liposomal doxorubicin (PLD); Other Names: DOXIL
Experimental: Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2) Dose Level 1: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 1: Carfilzomib IV (1 dose level above MTD) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (1 dose level above MTD) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (1 dose level above MTD) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib. Dose Level 2: Carfilzomib IV (2 dose levels above MTD) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (2 dose levels above MTD) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (2 dose levels above MTD) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Drug: carfilzomib; Other Names: Kyprolis CFZ ; Drug: pegylated liposomal doxorubicin (PLD); Other Names: DOXIL
Experimental: Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2) Dose Level 2: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Drug: carfilzomib; Other Names: Kyprolis CFZ ; Drug: pegylated liposomal doxorubicin (PLD); Other Names: DOXIL
Experimental: Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2) Dose Level 3: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Drug: carfilzomib; Other Names: Kyprolis CFZ ; Drug: pegylated liposomal doxorubicin (PLD); Other Names: DOXIL
Experimental: Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone) Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Drug: carfilzomib; Other Names: Kyprolis CFZ ; Drug: pegylated liposomal doxorubicin (PLD); Other Names: DOXIL ; Drug: Dexamethasone; Other Names: Decadron
Experimental: Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone) Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Drug: carfilzomib; Other Names: Kyprolis CFZ ; Drug: pegylated liposomal doxorubicin (PLD); Other Names: DOXIL ; Drug: Dexamethasone; Other Names: Decadron

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Carfilzomib and Pegylated Liposomal Doxorubicin (Phase I - Part 1). [28 days (completion of first cycle of all Phase I - Part 1 patients)]

   MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level. Please note that the maximum tolerated dose of carfilzomib and pegylated liposomal doxorubicin was not reached. The data below is the recommended dosage for further studies.

2. Maximum Tolerated Dose (MTD) of Carfilzomib and PLD (Phase I - Part 2). [28 days (completion of first cycle of all Phase I - Part 2 patients)]

   -MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level.

3. Maximum Tolerated Dose (MTD) of Dexamethasone (Phase I - Part 2). [28 days (completion of first cycle of all Phase I - Part 2 patients)]

   -MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level.

4. Phase 2 - Efficacy of Carfilzomib in Combination With PLD and Dexamethasone as Measured by the Percentage of Participants With Confirmed Tumor Responses [Completion of treatment (median number of cycles was 9.5 (range 1-34))]

   -A confirmed response is defined to be a complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG Criteria.

5. Phase 2 - Toxicity of Carfilzomib in Combination With PLD and Dexamethasone as Measured by Number of Participants Who Experience Grade 3/4 Toxicity [Through 30 days after completion of treatment (median number of cycles was 9.5 (range 1-34))]

Secondary Outcome Measures

1. Median Overall Survival [Completion of follow-up (median of 23.3 months)]

2. Progression-free Survival Time (Phase 2 Only) [Through completion of follow-up (median follow-up was 23.3 months)]

   -Progression per IMWG Criteria

3. Median Duration of Overall Response [Through completion of follow-up (median follow-up was 23.3 months)]

   For participants with confirmed tumor responses A confirmed response is defined to be a complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG Criteria

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed diagnosis of multiple myeloma with a measurable disease parameter at time of screening; a measurable disease parameter is defined as one or more of the following:

• Serum monoclonal protein >= 0.5 g/dl

• 24 hour urine monoclonal protein >= 0.2 g/24 hour

• Serum free light chain ratio > 5 x normal ratio with an absolute difference of 10mg/dl between the involved and uninvolved free light chain

• Soft tissue plasmacytoma >= 2 cm measurable by either physical examination and/or applicable radiographs (e.g. magnetic resonance imaging [MRI], computed tomography [CT], etc)

• Bone Marrow Plasma Cells >= 30%

• Documentation of at least one line of prior myeloma therapy now with relapsed or refractory disease requiring re-treatment

• At least 18 years of age at the time of signing the informed consent.

• Performance status of Eastern Cooperative Oncology Group (ECOG) =< 2 or Karnofsky >= 60%; participants with lower performance status based solely on bone pain secondary to multiple myeloma will be eligible

• Required laboratory values

• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) and aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 2.5 x the upper limit of the institutional normal value (ULN)

• Total bilirubin =< 1.5 x upper limit of normal (ULN)

• Absolute neutrophil count (ANC) >= 1,000

• Hemoglobin >= 8 g/dl

• Platelets >= 50,000

• Creatinine clearance > 15 ml/minute using Cockcroft-Gault formula

• For those participants receiving warfarin (Coumadin), unfractionated heparin, or low-molecular weight heparin therapy, the applicable coagulation parameter that is being monitored must be within the accepted therapeutic ranges for those indications

• Transfusions and/or growth factor dependent participants are not excluded if the above parameters can be achieved with such support

• Females of childbearing potential (FCBP) must agree to refrain from becoming pregnant while on study drug and for 3 months after discontinuation from study drug, and must agree to use adequate contraception including hormonal contraception, (i.e. birth control pills, etc), barrier method contraception (i.e. condoms), or abstinence during that time frame; FCBP must agree to regular pregnancy testing during this timeframe; inclusion of FCBP requires two negative pregnancy tests prior to enrollment. All women, regardless of age, should be considered FCBP unless they are surgically sterile (post hysterectomy, post bilateral oophorectomy, etc) or have been naturally post menopausal for >= 24 consecutive months

• Men engaging in sexual intercourse with a FCBP must agree to use adequate contraception including hormonal contraception, (i.e. birth control pills, etc), barrier method contraception (i.e. condoms), or abstinence while on study drug and for 3 months after discontinuation from study drug

• Ability to understand and willing to sign a written informed consent document

Exclusion Criteria:

• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)

• Plasma Cell Leukemia

• Waldenstrom's macroglobulinemia

• Pregnant or lactating females

• Use of any anti-myeloma drug therapy within 14 days of initiation of study drug treatment excluding corticosteroids if given for an indication other than myeloma; bisphosphonates are not considered anti-myeloma drugs

• Participation in an investigational therapeutic study within 14 days of initiation of study drug treatment

• Radiotherapy to multiple sites or immunotherapy within 14 days of initiation of study drug treatment (localized radiotherapy to a single site at least 7 days before start is permissible)

• Major surgery within 14 days of initiation of study drug treatment

• Participants in whom the required program of oral (PO) and IV fluid hydration is contraindicated

• Prior history of a hypersensitivity reaction to PLD, doxorubicin, bortezomib, carfilzomib, or liposomal drug formulations other than PLD; history of reactions to liposomal drug formulations other than PLD should be evaluated individually and if their reactions were felt to have been due to the encapsulated agent, rather than the liposomal component itself they should be excluded at the discretion of the investigators

• Participants who are known to have active hepatitis A, B, or C viral infection may not participate in this study; active disease is defined as participants with a known viral hepatitis whose liver function tests are elevated

• Known human immunodeficiency virus (HIV)-seropositive and are taking anti-retrovirals may not participate in this study; participants who are HIV-seropositive and not on anti-retroviral therapy and who otherwise meet the inclusion/exclusion criteria will be eligible for the study

• Compromised cardiovascular function defined as any of the following:

• Electrocardiogram (EKG) evidence of acute ischemia

• EKG evidence of medically significant conduction system abnormalities

• History of myocardial infarction within the last 6 months

• Unstable angina pectoris or cardiac arrhythmia

• History of Class 3 or Class 4 New York Heart Association Congestive Heart Failure within 6 months of enrollment on study

• Left ventricular ejection fraction (LVEF) < 45% by either echocardiography or radionuclide-based multiple gated acquisition (Echo or MUGA)

• Uncontrolled concurrent illness including: other hematologic or non-hematologic malignancy, active infection, or uncontrolled diabetes

• Any significant psychological, medical, or surgical condition thought to compromise the participant, the study, or prevent informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Washington University School of Medicine	Saint Louis	Missouri	United States	63110

Sponsors and Collaborators

• Washington University School of Medicine

Investigators

• Principal Investigator: Ravi Vij, M.D., Washington University School of Medicine

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Dec 4, 2015

More Information

Additional Information:

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Publications

None provided.

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT01246063
• Other Study ID Numbers: 201102043
• First Posted: Nov 23, 2010
• Last Update Posted: Apr 8, 2019
• Last Verified: Apr 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Doxorubicin; Liposomal doxorubicin

Study Results

Participant Flow

Recruitment Details	The study opened to participant enrollment on 05/14/2012 and closed to participant enrollment on 08/02/2016.

Arm/Group Title	Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2)	Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2)	Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2)	Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2)	Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone)	Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone)
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Dose Level 1: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Dose Level 2: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Dose Level 3: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Period Title: Overall Study
STARTED	3	4	4	5	7	17
COMPLETED	3	4	4	5	7	17
NOT COMPLETED	0	0	0	0	0	0

Baseline Characteristics

Arm/Group Title	Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2)	Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2)	Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2)	Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2)	Phase I-Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone)	Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone)	Total
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (27 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Dose Level 1: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (36 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Dose Level 2: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (45 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Dose Level 3: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (56 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Total of all reporting groups
Overall Participants	3	4	4	5	7	17	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	65	66.5	72	57	63	65	65
Sex: Female, Male (Count of Participants)
Female	2 66.7%	2 50%	2 50%	5 100%	5 71.4%	7 41.2%	23 57.5%
Male	1 33.3%	2 50%	2 50%	0 0%	2 28.6%	10 58.8%	17 42.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	1 33.3%	4 100%	4 100%	4 80%	7 100%	17 100%	37 92.5%
Unknown or Not Reported	2 66.7%	0 0%	0 0%	1 20%	0 0%	0 0%	3 7.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 33.3%	1 25%	1 25%	1 20%	0 0%	5 29.4%	9 22.5%
White	2 66.7%	3 75%	3 75%	4 80%	7 100%	11 64.7%	30 75%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	1 5.9%	1 2.5%
Region of Enrollment (Count of Participants)
United States	3 100%	4 100%	4 100%	5 100%	7 100%	17 100%	40 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Carfilzomib and Pegylated Liposomal Doxorubicin (Phase I - Part 1).
Description	MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level. Please note that the maximum tolerated dose of carfilzomib and pegylated liposomal doxorubicin was not reached. The data below is the recommended dosage for further studies.
Time Frame	28 days (completion of first cycle of all Phase I - Part 1 patients)

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Phase I - Part 1 portion of this study were the only evaluable participants for this outcome measure.

Arm/Group Title	Phase I - Part 1	Phase I - Part 2	Phase 2
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 1: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 2: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 3: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Measure Participants	16	0	0
Carfilzomib Recommended Dose	56
Pegylated liposomal doxorubicin recommended dose	30

2. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Carfilzomib and PLD (Phase I - Part 2).
Description	-MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level.
Time Frame	28 days (completion of first cycle of all Phase I - Part 2 patients)

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Phase I - Part 2 portion of this study were the only evaluable participants for this outcome measure.

Arm/Group Title	Phase I - Part 1	Phase I - Part 2	Phase 2
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 1: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 2: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 3: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Measure Participants	0	7	0
Carfilzomib dose	56
Pegylated liposomal doxorubicin dose	30

3. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Dexamethasone (Phase I - Part 2).
Description	-MTD is the maximum tolerated dose level tested unless dose limiting toxicity (DLT) are observed during Cycle 1. If DLT is observed, MTD will be the next lower dose level.
Time Frame	28 days (completion of first cycle of all Phase I - Part 2 patients)

Outcome Measure Data

Analysis Population Description

Participants enrolled in the Phase I - Part 2 portion of this study were the only evaluable participants for this outcome measure.

Arm/Group Title	Phase I - Part 1	Phase I - Part 2	Phase 2
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 1: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 2: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 3: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Measure Participants	0	7	0
Number [mg]	20

4. Primary Outcome

Title	Phase 2 - Efficacy of Carfilzomib in Combination With PLD and Dexamethasone as Measured by the Percentage of Participants With Confirmed Tumor Responses
Description	-A confirmed response is defined to be a complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG Criteria.
Time Frame	Completion of treatment (median number of cycles was 9.5 (range 1-34))

Outcome Measure Data

Analysis Population Description

For this outcome measure the Phase I - Part 1 Dose Level 3 and Phase I - Part 2 participants were combined with the Phase 2 participants as they received the same dosing of carfilzomib. The remaining Phase I - Part 1 participants were not evaluable for this outcome measure.

Arm/Group Title	Phase I - Part 1	Phase 2 (Includes Phase I - Part 2 Participants)
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 1: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 2: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 3: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Phase I Part 2 Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib. Phase 2: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Measure Participants	0	24
Count of Participants [Participants]	20 666.7%

5. Primary Outcome

Title	Phase 2 - Toxicity of Carfilzomib in Combination With PLD and Dexamethasone as Measured by Number of Participants Who Experience Grade 3/4 Toxicity
Time Frame	Through 30 days after completion of treatment (median number of cycles was 9.5 (range 1-34))

Outcome Measure Data

Analysis Population Description

For this outcome measure the Phase I - Part 2 participants were combined with the Phase 2 participants as they received the same dosing regimen. Phase I - Part 1 participants were not evaluable for this outcome measure.

Arm/Group Title	Phase I - Part 1	Phase 2 (Includes Phase I - Part 2 Participants)
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 1: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 2: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 3: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Phase I Part 2 Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib. Phase 2: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Measure Participants	0	24
Count of Participants [Participants]	22 733.3%

6. Secondary Outcome

Title	Median Overall Survival
Time Frame	Completion of follow-up (median of 23.3 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2)	Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2)	Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2)	Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2)	Phase I-Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone)	Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone)
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (27 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Dose Level 1: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (36 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Dose Level 2: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (45 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Dose Level 3: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (56 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Measure Participants	3	4	4	5	7	17
Median (95% Confidence Interval) [months]	25.490	18.780	11.610	32.340	18.720	NA

7. Secondary Outcome

Title	Progression-free Survival Time (Phase 2 Only)
Description	-Progression per IMWG Criteria
Time Frame	Through completion of follow-up (median follow-up was 23.3 months)

Outcome Measure Data

Analysis Population Description

This outcome measure is for Phase 2 (including Phase I Part 2) participants only. Phase I Part 2 and Phase 2 participants who began alternative anti-multiple myeloma treatment prior to progression were censored.

Arm/Group Title	Phase I - Part 1	Phase 2 (Includes Phase I - Part 2 Participants)
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 1: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 2: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6. Dose Level 3: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.	Phase I Part 2 Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib. Phase 2: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Measure Participants	0	8
Median (95% Confidence Interval) [months]	13.4

8. Secondary Outcome

Title	Median Duration of Overall Response
Description	For participants with confirmed tumor responses A confirmed response is defined to be a complete response (CR), very good partial response (VGPR), or partial response (PR) per IMWG Criteria
Time Frame	Through completion of follow-up (median follow-up was 23.3 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2)	Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2)	Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2)	Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2)	Phase I-Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone)	Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone)
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (27 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Dose Level 1: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (36 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Dose Level 2: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (45 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Dose Level 3: Carfilzomib IV (20 mg/m2) D1&D2 of C1 and carfilzomib IV (56 mg/m2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m2)D8 C1-6.	Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.	Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
Measure Participants	1	2	2	4	5	15
Median (95% Confidence Interval) [months]	6.090	6.840	3.420	13.130	9.440	23.950

Adverse Events

Time Frame	Adverse events were followed from first day of study treatment until 30 days following the last day of study treatment or until the start of a new chemotherapy, whichever is sooner. Median number of cycles was 9.5 (range 1-34 cycles). All-cause mortality data was collected from first day of study treatment until completion of treatment.
Arm/Group Title	Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2)		Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2)		Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2)		Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2)		Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone)		Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone)
Arm/Group Description	Dose Level 0: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (27 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (27 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (27 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.		Dose Level 1: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (36 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (36 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (36 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.		Dose Level 2: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (45 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (45 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (45 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.		Dose Level 3: Carfilzomib IV (20 mg/m^2) D1&D2 of C1 and carfilzomib IV (56 mg/m^2)D8, D9, D15, D16 of C1. Carfilzomib IV (56 mg/m^2) D1, D2, D8, D9, D15, D16 C2-6. Carfilzomib IV (56 mg/m^2)D1, D2, D8, D15, D22 C7+. PLD IV (30 mg/m^2)D8 C1-6.		Cohort 0: Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.		Carfilzomib IV (56 mg/^2 - Phase 1 Part 1) D1, D2, D8, D9, D15, D16 C1-6. Carfilzomib IV (56 mg/m^2 - Phase 1 Part 1) D1, D8, D15, D22 C7 and subsequent cycles. PLD IV (30 mg/m^2 - Phase 1 Part 1) D8 of each cycle. Dexamethasone 20 mg IV or PO same schedule as carfilzomib.
All Cause Mortality
	Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2)		Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2)		Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2)		Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2)		Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone)		Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone)
	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	0/3 (0%)		0/4 (0%)		2/4 (50%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Serious Adverse Events
	Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2)		Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2)		Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2)		Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2)		Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone)		Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone)
	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	2/3 (66.7%)		3/4 (75%)		4/4 (100%)		3/5 (60%)		2/7 (28.6%)		10/17 (58.8%)
Blood and lymphatic system disorders
Thrombotic thrombocytopenic purpura	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Cardiac disorders
Aortic valve disease	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Supraventricular tachycardia	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Gastrointestinal disorders
Diarrhea	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Diverticulitis	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
General disorders
Fever	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		1/7 (14.3%)		1/17 (5.9%)
Infusion related reaction	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Pain	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Weakness	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Infections and infestations
Acute bronchitis	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Pneumonia	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
RSV infection	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Sepsis	0/3 (0%)		0/4 (0%)		3/4 (75%)		0/5 (0%)		1/7 (14.3%)		1/17 (5.9%)
Skin infection (cellulitis)	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Skin infection (MRSA)	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Skin infection (shingles)	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Upper respiratory infection	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/7 (14.3%)		4/17 (23.5%)
Urinary tract infection	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		2/17 (11.8%)
Injury, poisoning and procedural complications
Polypharmacy	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Metabolism and nutrition disorders
Dehydration	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Bone pain	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Left hip pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Nervous system disorders
Acute encephalopathy	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Posterior reversible encephalopathy syndrome	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Renal and urinary disorders
Acute rental failure	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
COPD exacerbation	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Dyspnea	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Dyspnea (COPD exacerbation)	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Hypoxia	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Pneumonitis	0/3 (0%)		0/4 (0%)		1/4 (25%)		1/5 (20%)		2/7 (28.6%)		0/17 (0%)
Respiratory failure	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Vascular disorders
Thromboembolic event (DVT)	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Other (Not Including Serious) Adverse Events
	Phase I - Part 1 Dose Level 0 (Carfilzomib 20/27 mg/m^2)		Phase I - Part 1 Dose Level 1 (Carfilzomib 20/36 mg/m^2)		Phase I - Part 1 Dose Level 2 (Carfilzomib 20/45 mg/m^2)		Phase I - Part 1 Dose Level 3 (Carfilzomib 20/56 mg/^2)		Phase I -Part 2 Cohort 0 (Carfilzomib 56 mg/m^2+Dexamethasone)		Phase 2 (Carfilzomib 56 mg/m^2+ Dexamethasone)
	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%)		4/4 (100%)		4/4 (100%)		5/5 (100%)		7/7 (100%)		17/17 (100%)
Blood and lymphatic system disorders
Anemia	0/3 (0%)		3/4 (75%)		4/4 (100%)		4/5 (80%)		6/7 (85.7%)		14/17 (82.4%)
Hemolysis	0/3 (0%)		0/4 (0%)		0/4 (0%)		2/5 (40%)		0/7 (0%)		2/17 (11.8%)
Lymph node swelling	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Cardiac disorders
Heart failure	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		1/17 (5.9%)
Heart murmur	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Myocardial infarction	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Sinus bradycardia	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Sinus tachycardia	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/7 (14.3%)		1/17 (5.9%)
Tricuspid valve disease	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Ear and labyrinth disorders
Ear pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		2/7 (28.6%)		2/17 (11.8%)
Right ear fullness	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Tinnitus	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		1/17 (5.9%)
Vertigo	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Eye disorders
Blurred vision	0/3 (0%)		0/4 (0%)		2/4 (50%)		0/5 (0%)		1/7 (14.3%)		1/17 (5.9%)
Cataract	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		4/17 (23.5%)
Conjunctivitis	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Dry eye	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Eye erythema	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Flashing lights	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Subconjunctival hemorrhage	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Watering eyes	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Gastrointestinal disorders
Abdominal distension	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Abdominal pain	1/3 (33.3%)		1/4 (25%)		2/4 (50%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Anal fistula	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Anal pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Bloating	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		2/7 (28.6%)		0/17 (0%)
Constipation	3/3 (100%)		3/4 (75%)		3/4 (75%)		2/5 (40%)		1/7 (14.3%)		6/17 (35.3%)
Dental caries	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Diarrhea	1/3 (33.3%)		0/4 (0%)		3/4 (75%)		5/5 (100%)		4/7 (57.1%)		9/17 (52.9%)
Diverticulitis	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Dyspepsia	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/7 (14.3%)		3/17 (17.6%)
Dysphagia	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Fecal incontinence	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Gastroenteritis	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		2/17 (11.8%)
Gastroesophageal reflux disease	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Hemorrhoids	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		2/17 (11.8%)
Hypersalivating	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Ileus	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Indigestion	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Mouth sores	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Mucositits oral	0/3 (0%)		0/4 (0%)		2/4 (50%)		4/5 (80%)		1/7 (14.3%)		6/17 (35.3%)
Nausea	3/3 (100%)		1/4 (25%)		3/4 (75%)		4/5 (80%)		4/7 (57.1%)		9/17 (52.9%)
Oral dysesthesia	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Oral pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Rectal hemorrhage	0/3 (0%)		0/4 (0%)		2/4 (50%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Rectal pain	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Rectal ulcer	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Sores at corner of mouth	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Stomach flu	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Stomach pain	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Stomach virus	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Toothache	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		3/17 (17.6%)
Upset stomach	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Vomiting	3/3 (100%)		0/4 (0%)		2/4 (50%)		2/5 (40%)		6/7 (85.7%)		4/17 (23.5%)
General disorders
Achy	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Black spot-tongue	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Chills	0/3 (0%)		0/4 (0%)		2/4 (50%)		4/5 (80%)		1/7 (14.3%)		4/17 (23.5%)
Edema face	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		1/17 (5.9%)
Edema limbs	2/3 (66.7%)		1/4 (25%)		1/4 (25%)		1/5 (20%)		0/7 (0%)		2/17 (11.8%)
Fatigue	3/3 (100%)		2/4 (50%)		3/4 (75%)		5/5 (100%)		5/7 (71.4%)		10/17 (58.8%)
Fever	1/3 (33.3%)		0/4 (0%)		3/4 (75%)		4/5 (80%)		2/7 (28.6%)		8/17 (47.1%)
Flu Like Symptoms	1/3 (33.3%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Generalized pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		3/17 (17.6%)
Groin pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Hand pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
IV site swelling	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Infusion related reaction	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Infusion site extravasation	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/7 (28.6%)		5/17 (29.4%)
Injection like reaction	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Kidney pain cramping	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Legs/jaw/head pain	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Localized edema	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		1/7 (14.3%)		5/17 (29.4%)
Localized edema-feet	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Malaise	0/3 (0%)		0/4 (0%)		1/4 (25%)		2/5 (40%)		0/7 (0%)		2/17 (11.8%)
Neck edema	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Night sweats	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		2/7 (28.6%)		0/17 (0%)
Non-cardiac chest pain	1/3 (33.3%)		0/4 (0%)		1/4 (25%)		1/5 (20%)		0/7 (0%)		2/17 (11.8%)
Pain	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Rib cage pain	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Shoulder blade pain	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Sweating	0/3 (0%)		0/4 (0%)		1/4 (25%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Pain-head to toe	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Hepatobiliary disorders
Gallstones	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Infections and infestations
Anorectal infection	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Bone infection	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
C. diff colitis	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Conjunctivitis infective	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		1/7 (14.3%)		1/17 (5.9%)
Finger wart	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Groin infection	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Lip infection	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Lung infection	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Nail infection	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		1/17 (5.9%)
Oral candidiasis/thrush	0/3 (0%)		0/4 (0%)		2/4 (50%)		1/5 (20%)		1/7 (14.3%)		5/17 (29.4%)
Otitis media	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Perianal abscess	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Salivary gland infection	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Sinusitis	0/3 (0%)		1/4 (25%)		0/4 (0%)		3/5 (60%)		2/7 (28.6%)		5/17 (29.4%)
Skin infection	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Stool (+) VRE	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Stool (+) norovirus	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Stye	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Tooth infection	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Upper respiratory infection	2/3 (66.7%)		0/4 (0%)		2/4 (50%)		4/5 (80%)		3/7 (42.9%)		10/17 (58.8%)
Urinary tract infection	1/3 (33.3%)		0/4 (0%)		2/4 (50%)		0/5 (0%)		1/7 (14.3%)		4/17 (23.5%)
Viral illness	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Injury, poisoning and procedural complications
Bruising	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		2/17 (11.8%)
Elbow wound	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Fall	1/3 (33.3%)		0/4 (0%)		3/4 (75%)		2/5 (40%)		0/7 (0%)		3/17 (17.6%)
Fracture	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Great toe wound	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Phalangeal fracture	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Rib fractures	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Right foot fracture	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Spinal fracture - pathologic	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Investigations
Alanine aminotransferase increased	1/3 (33.3%)		0/4 (0%)		3/4 (75%)		3/5 (60%)		3/7 (42.9%)		10/17 (58.8%)
Alkaline phosphatase increased	0/3 (0%)		0/4 (0%)		2/4 (50%)		1/5 (20%)		3/7 (42.9%)		2/17 (11.8%)
Aspartate aminotransferase increased	2/3 (66.7%)		1/4 (25%)		3/4 (75%)		3/5 (60%)		4/7 (57.1%)		14/17 (82.4%)
Blood bilirubin increased	0/3 (0%)		0/4 (0%)		1/4 (25%)		2/5 (40%)		2/7 (28.6%)		5/17 (29.4%)
CPK increased	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		1/17 (5.9%)
Cardiac troponin I increased	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		2/17 (11.8%)
Cholesterol high	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		3/17 (17.6%)
Creatinine increased	3/3 (100%)		2/4 (50%)		3/4 (75%)		3/5 (60%)		5/7 (71.4%)		8/17 (47.1%)
INR increased	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		1/7 (14.3%)		6/17 (35.3%)
Lipase increased	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		1/17 (5.9%)
Lymphocyte count decreased	3/3 (100%)		1/4 (25%)		3/4 (75%)		4/5 (80%)		7/7 (100%)		17/17 (100%)
Lymphocyte count increased	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Neutrophil count decreased	1/3 (33.3%)		2/4 (50%)		1/4 (25%)		4/5 (80%)		6/7 (85.7%)		12/17 (70.6%)
Platelet count decreased	2/3 (66.7%)		1/4 (25%)		3/4 (75%)		5/5 (100%)		7/7 (100%)		17/17 (100%)
Serum amylase increased	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Weight gain	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		2/7 (28.6%)		1/17 (5.9%)
Weight loss	0/3 (0%)		1/4 (25%)		0/4 (0%)		3/5 (60%)		0/7 (0%)		5/17 (29.4%)
White blood cell decreased	1/3 (33.3%)		2/4 (50%)		3/4 (75%)		3/5 (60%)		5/7 (71.4%)		17/17 (100%)
Metabolism and nutrition disorders
Anorexia	2/3 (66.7%)		1/4 (25%)		2/4 (50%)		4/5 (80%)		2/7 (28.6%)		3/17 (17.6%)
Dehydration	0/3 (0%)		0/4 (0%)		1/4 (25%)		3/5 (60%)		3/7 (42.9%)		6/17 (35.3%)
Diabetes type 2	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Hypercalcemia	2/3 (66.7%)		1/4 (25%)		1/4 (25%)		2/5 (40%)		3/7 (42.9%)		9/17 (52.9%)
Hyperglycemia	0/3 (0%)		3/4 (75%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		3/17 (17.6%)
Hyperkalemia	0/3 (0%)		0/4 (0%)		1/4 (25%)		2/5 (40%)		1/7 (14.3%)		7/17 (41.2%)
Hypermagnesemia	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/7 (28.6%)		3/17 (17.6%)
Hypernatremia	0/3 (0%)		2/4 (50%)		1/4 (25%)		1/5 (20%)		1/7 (14.3%)		8/17 (47.1%)
Hyperphosphatemia	0/3 (0%)		0/4 (0%)		1/4 (25%)		3/5 (60%)		5/7 (71.4%)		12/17 (70.6%)
Hypertriglyceridemia	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		2/17 (11.8%)
Hyperuricemia	1/3 (33.3%)		1/4 (25%)		2/4 (50%)		1/5 (20%)		3/7 (42.9%)		9/17 (52.9%)
Hypoalbuminemia	1/3 (33.3%)		1/4 (25%)		3/4 (75%)		2/5 (40%)		4/7 (57.1%)		11/17 (64.7%)
Hypocalcemia	3/3 (100%)		3/4 (75%)		4/4 (100%)		5/5 (100%)		5/7 (71.4%)		6/17 (35.3%)
Hypoglycemia	1/3 (33.3%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		3/17 (17.6%)
Hypokalemia	2/3 (66.7%)		1/4 (25%)		2/4 (50%)		4/5 (80%)		4/7 (57.1%)		4/17 (23.5%)
Hypomagnesemia	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Hyponatremia	2/3 (66.7%)		1/4 (25%)		2/4 (50%)		4/5 (80%)		1/7 (14.3%)		8/17 (47.1%)
Hypophosphatemia	2/3 (66.7%)		1/4 (25%)		3/4 (75%)		2/5 (40%)		3/7 (42.9%)		12/17 (70.6%)
Iron overload	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Musculoskeletal and connective tissue disorders
Achiness hips	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Arthralgia	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		2/17 (11.8%)
Back pain	2/3 (66.7%)		1/4 (25%)		2/4 (50%)		2/5 (40%)		1/7 (14.3%)		2/17 (11.8%)
Body aches	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		1/7 (14.3%)		0/17 (0%)
Bone pain	1/3 (33.3%)		0/4 (0%)		1/4 (25%)		2/5 (40%)		1/7 (14.3%)		1/17 (5.9%)
Buttock pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		1/17 (5.9%)
Cramping arms, hands, and feet	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Cramping hands and feet	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Elbow pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Flank pain	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		2/17 (11.8%)
Foot pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Generalized muscle weakness	1/3 (33.3%)		0/4 (0%)		2/4 (50%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Hip pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		3/17 (17.6%)
Hip/leg pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Intercostal pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Joint range of motion decreased	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Joint range of motion decreased in lumbar spine	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Leg cramps	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		1/17 (5.9%)
Muscle cramps/spasms	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Muscle spasms-hands	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Muscle weakness-hands	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Muscle weakness/heaviness lower limbs	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Myalgia	0/3 (0%)		0/4 (0%)		1/4 (25%)		1/5 (20%)		1/7 (14.3%)		2/17 (11.8%)
Neck pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		3/17 (17.6%)
Osteonecrosis of palate	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Pain in extremity	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		2/7 (28.6%)		0/17 (0%)
Rib pain	0/3 (0%)		0/4 (0%)		1/4 (25%)		1/5 (20%)		0/7 (0%)		2/17 (11.8%)
Right armpit pain	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Right rib cage pain	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Right side pain with deep breath	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Rotator cuff tear full/partial	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Shoulder pain	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/7 (14.3%)		2/17 (11.8%)
Shoulder spasm	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Warm spot on thigh	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Wrist pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BCCA Nasal Ala	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Enlarging pulmonary nodule	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
T10 lesion-invasion into spinal cord	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Tumor pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Nervous system disorders
Akathisia	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Dizziness	0/3 (0%)		0/4 (0%)		1/4 (25%)		2/5 (40%)		2/7 (28.6%)		5/17 (29.4%)
Dysgeusia	0/3 (0%)		0/4 (0%)		1/4 (25%)		2/5 (40%)		0/7 (0%)		0/17 (0%)
Facial droop	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		2/17 (11.8%)
Fingertip sensitivity	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Headache	1/3 (33.3%)		1/4 (25%)		1/4 (25%)		3/5 (60%)		4/7 (57.1%)		8/17 (47.1%)
Intracranial hemorrhage	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Lethargy	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Memory impairment	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Neuralgia-shingles pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Paresthesia	0/3 (0%)		0/4 (0%)		1/4 (25%)		2/5 (40%)		3/7 (42.9%)		2/17 (11.8%)
Peripheral sensory neuropathy	3/3 (100%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		2/7 (28.6%)		3/17 (17.6%)
Sinus pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Spasticity	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Syncope	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		2/7 (28.6%)		2/17 (11.8%)
Tingling/numbness lower jaw	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Tremor	2/3 (66.7%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Psychiatric disorders
Agitation	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Anxiety	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		2/7 (28.6%)		3/17 (17.6%)
Concentration impairment	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Confusion	1/3 (33.3%)		1/4 (25%)		3/4 (75%)		2/5 (40%)		1/7 (14.3%)		4/17 (23.5%)
Delirium	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Hallucinations	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Insomnia	0/3 (0%)		1/4 (25%)		1/4 (25%)		1/5 (20%)		3/7 (42.9%)		9/17 (52.9%)
Renal and urinary disorders
ATN	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Acute kidney injury	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Bladder pain	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Cystitis noninfective	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Dysuria	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Hematuria	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Proteinuria	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Urinary frequency	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Urinary incontinence	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Urinary retention	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Urinary urgency	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Reproductive system and breast disorders
Scrotal pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Vaginal hemorrhage	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Atelectasis	0/3 (0%)		1/4 (25%)		2/4 (50%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Congestion head/chest	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Cough	0/3 (0%)		2/4 (50%)		3/4 (75%)		4/5 (80%)		3/7 (42.9%)		10/17 (58.8%)
Dypnea	1/3 (33.3%)		2/4 (50%)		4/4 (100%)		3/5 (60%)		4/7 (57.1%)		8/17 (47.1%)
Epistaxis	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		3/17 (17.6%)
Hiccups	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Hypoxia	1/3 (33.3%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Indeterminate lung nodules	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Nasal congestion	0/3 (0%)		1/4 (25%)		1/4 (25%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Pleural effusion	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Pleuritic pain	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Pneumonitis	0/3 (0%)		1/4 (25%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		3/17 (17.6%)
Postnasal drip	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		3/17 (17.6%)
Productive cough	0/3 (0%)		1/4 (25%)		2/4 (50%)		0/5 (0%)		3/7 (42.9%)		9/17 (52.9%)
Pulmonary edema	0/3 (0%)		1/4 (25%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Respiratory distress-tachypnea	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Rhinorrhea	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		1/7 (14.3%)		0/17 (0%)
Sore throat	1/3 (33.3%)		0/4 (0%)		1/4 (25%)		3/5 (60%)		1/7 (14.3%)		4/17 (23.5%)
Wheezing	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		1/17 (5.9%)
Skin and subcutaneous tissue disorders
"Pink Areas" palms of hands	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Alopecia	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Blood blisters	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		2/17 (11.8%)
Bug bites	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Cat bite	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Dry skin	0/3 (0%)		1/4 (25%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		3/17 (17.6%)
Enlarging mole	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Erythema Multiforme	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Erythematous rash	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Flaking skin on hands	1/3 (33.3%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Foot blisters (after excessive walking)	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Head nodule	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Nail changes	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Open area-left eyebrow	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Palmar-plantar erythrodysesthesia syndrome	1/3 (33.3%)		0/4 (0%)		2/4 (50%)		1/5 (20%)		0/7 (0%)		2/17 (11.8%)
Periorbital edema	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		2/17 (11.8%)
Petechial rash	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Poison ivy	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/7 (14.3%)		1/17 (5.9%)
Pressure ulcers - buttocks	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Pruritus	0/3 (0%)		1/4 (25%)		0/4 (0%)		1/5 (20%)		2/7 (28.6%)		1/17 (5.9%)
Rash aceniform	0/3 (0%)		1/4 (25%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Rash arms	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Rash maculo-papular	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Rash-back	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Skin blisters s/p lesion removal	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Skin tear	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Skin ulceration	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Swelling from bug bites	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Surgical and medical procedures
Colonoscopy	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Cytoscopy with bladder biopsies	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		0/7 (0%)		0/17 (0%)
Excision osteonecrosis-maxilla	0/3 (0%)		0/4 (0%)		0/4 (0%)		1/5 (20%)		0/7 (0%)		0/17 (0%)
Foot surgery	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Shoulder rotator cuff repair-right	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Urethral sling placement	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		0/7 (0%)		1/17 (5.9%)
Vascular disorders
Flushing	0/3 (0%)		0/4 (0%)		0/4 (0%)		2/5 (40%)		0/7 (0%)		1/17 (5.9%)
Flushing-face	0/3 (0%)		0/4 (0%)		0/4 (0%)		0/5 (0%)		1/7 (14.3%)		0/17 (0%)
Hot flashes	0/3 (0%)		0/4 (0%)		1/4 (25%)		1/5 (20%)		1/7 (14.3%)		1/17 (5.9%)
Hypertension	2/3 (66.7%)		0/4 (0%)		1/4 (25%)		3/5 (60%)		1/7 (14.3%)		6/17 (35.3%)
Hypotension	0/3 (0%)		0/4 (0%)		2/4 (50%)		2/5 (40%)		0/7 (0%)		3/17 (17.6%)
Thromboembolic event - DVT	0/3 (0%)		0/4 (0%)		1/4 (25%)		0/5 (0%)		1/7 (14.3%)		4/17 (23.5%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

All Principal Investigators ARE 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.