Phase 1/2 Study of Carfilzomib for the Prevention of Relapse and GVHD in Allo-HCT for Hematologic Malignancies

• Sponsor: University of Michigan Rogel Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02145403
• Collaborator: (none)
• Enrollment: 53
• Location: 1
• Arm: 1
• Actual Duration (Months): 72.5
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The investigators hypothesize that adding carfilzomib to standard conditioning regimen for allo-HCT for advanced or high-risk hematologic malignancies will decrease post-transplant relapse and treatment-related mortality by decreasing severe GVHD, leading to overall improvement in transplant outcomes.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Malignancies; Relapse; Graft-Versus-Host Disease	Drug: Carfilzomib; Drug: Tacrolimus	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 53 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of Carfilzomib for the Prevention of Relapse and Graft-versus-host Disease in Allogeneic Hematopoietic Cell Transplantation for High-risk Hematologic Malignancies
• Actual Study Start Date: Oct 1, 2014
• Actual Primary Completion Date: Nov 26, 2018
• Actual Study Completion Date: Oct 16, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Carfilzomib Carfilzomib will be administered IV over 30 minutes, starting at dose level 1 (20 mg/m2 IV) on Day +1, +2, +6 and +7.

Drug: Carfilzomib; Carfilzomib will be administered starting at dose level 1 (20 mg/m2 IV) on day +1, +2, +6 and +7. Dose escalation will be performed on the day +6 and day +7 doses only in each dose level. Day +1 and day+2 doses will be fixed at 20 mg/m2 IV in all dose levels.; Other Names: Kyprolis® ; Drug: Tacrolimus; Tacrolimus will be administered at 0.03 mg/kg continuous infusion over 24 hours, starting on day -3 as standard graft-versus-host disease prophylaxis.

Outcome Measures

Primary Outcome Measures

1. Phase I: Maximum Tolerated Dose (MTD) of Carfilzomib [Up to day 28]

   Subjects were enrolled on the first dose level (20 mg/m^2), following a standard 3+3 dose escalation. For any given dose level, if none of the 3 subjects developed a treatment-related dose limiting toxicity (DLT), defined per protocol, dose escalation would follow. If a DLT occurred in any given dose level, the cohort would be expanded to 6. Further dose escalation would be made only if DLTs occurred in <2 out of 6 subjects. If >=2 of 6 develop DLTs, dose de-escalation would be made to the previous level. The highest dose level at which no more than one of six participants experience a DLT defines the MTD.

2. Phase II: Kaplan-Meier Estimate of the Percentage of Patients Who Are Alive and Have Not Developed Any "Event" [1 year]

   Kaplan-Meier estimate of the percentage of patients who are alive and have not developed relapse/progression of primary disease or clinical grade III-IV acute graft-versus- host disease (GVHD) or chronic GVHD requiring systemic treatment. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.

Secondary Outcome Measures

1. Phase II: Kaplan-Meier Estimate for Progression/Relapse-free Survival Time [Up to 3 years]

   Time from day 0 to the date of the first progression/relapse. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.

2. Phase II: Kaplan-Meier Estimate for Overall Survival Time [Up to 3 years]

   The time from day 0 to the day of death from any cause. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.

3. Number of Regimen Related Toxicities (RRTs) [Up to 30 days post treatment]

   An RTT is defined as an adverse event (AE) that occurs within +37 days after transplant or 30 days after the last dose of carfilzomib (day +7), and is considered to be a direct consequence and a related event as a result of the combination of conditioning chemotherapy, GVHD prophylaxis regimen and carfilzomib.

4. Phase II: Cumulative Incidence of Acute GVHD [At day 180 post-transplant; data collected up to 3 years]

   The cumulative incidence of acute Graft Versus Host Disease (aGVHD). Events were assigned a severity grade using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4.0; lower values indicate least severe and higher values indicate most severe. Grades 2 - 4 and grades 3 - 4 events are reported. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.

5. Phase II: Cumulative Incidence of Chronic GVHD [Up to 3 years]

   The cumulative incidence of chronic Graft Versus Host Disease (GVHD). Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.

6. Phase II: Cumulative Incidence of Non-relapse Mortality [Up to 3 years]

   The cumulative incidence of non-relapse mortality. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Lymphoid or Myeloid malignancy requiring allogeneic hematopoietic cell transplantation

• Pathology review by the study institution is required

• Prior high-dose chemotherapy and autologous HCT(s) is (are) allowed

• Disease status: Stable disease or better at the time of enrollment

• Age: >18 and <70 years old at the time of transplant (< 71 years at transplant admission)

• Life expectancy ≥ 6 months after transplant

• A 8/8 or 7/8 HLA-matched donor is available

• Karnofsky Performance Status >70% (A measure of quality of life that ranges from 0 to 100 where 100 equals perfect health and 0 is death.)

• Adequate cardiac [LVEF (Left Ventricular Ejection Fraction) >0.4], pulmonary [FEV1 (Forced Expiratory Volume in 1 Second), FVC (Forced Vital Capacity), corrected DLCO (Diffusing Capacity) ≥ 50% predicted], hepatic [DB (Direct Bilirubin) <1.5xULN, AST (Aspartate Aminotransferase) / ALT (Alanine transaminase) ≤3xULN] and renal function [GFR (Glomerular Filtration Rate) ≥ 60 mL/min/1.73 m2]

Exclusion Criteria:

• Progressive disease

• Active central nervous system involvement by malignancy

• Non compliance to medications or medical instructions

• Lack of appropriate caregivers

• Life expectancy <6 months

• Pregnant or lactating females

• Uncontrolled infection requiring active treatment (systemic antibiotics, anti-virals, or anti-fungals) within 14 days

• HIV-1/HIV-2 or HTLV-1/HTLV-2 seropositivity

• Active hepatitis A, B or C infection

• Unstable angina or myocardial infarction within 6 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, uncontrolled or persistent atrial fibrillation/flutter, history of ventricular fibrillation, ventricular tachycardia/torsade de pointes, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker

• History of pulmonary hypertension

• Uncontrolled hypertension or uncontrolled diabetes mellitus

• Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen (PSA) levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas

• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)

• Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all available anti-microbial drugs or intolerance to IV hydration due to pre-existing pulmonary or cardiac impairment

• Subjects with pleural effusion requiring thoracentesis or ascites requiring paracentesis within 14 days prior to admission

• Uncontrolled psychiatric condition

• Any other clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan Hospital	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan Rogel Cancer Center

Investigators

• Principal Investigator: Attaphol Pawarode, M.D., University of Michgan Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 24, 2018

More Information

Publications

None provided.

• Responsible Party: University of Michigan Rogel Cancer Center
• ClinicalTrials.gov Identifier: NCT02145403
• Other Study ID Numbers: UMCC 2014.010; HUM00084170
• First Posted: May 22, 2014
• Last Update Posted: Jan 3, 2022
• Last Verified: Dec 1, 2021

• Keywords provided by University of Michigan Rogel Cancer Center: Allogeneic Transplantation; Carfilzomib; Relapse; Graft-Versus-Host Disease; Multiple Myeloma; Lymphoma; Leukemia
• Additional relevant MeSH terms: Neoplasms; Hematologic Neoplasms; Graft vs Host Disease; Recurrence; Tacrolimus

Study Results

Participant Flow

Pre-assignment Detail	Two patients who consented never began treatment.

Arm/Group Title	Dose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2	Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2	Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2	Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2
Arm/Group Description	Participants in all cohorts were administered 20 mg/m^2 of Carfilzomib on days +1 and +2, via intravenous catheter (IV) over 30 minutes. Cohort 1: Participants were administered 20 mg/m^2 of Carfilzomib on days +6 and +7. Participants in all cohorts were administered tacrolimus at 0.03 mg/kg continuous infusion over 24 hours, starting on day -3 as standard graft-versus-host disease prophylaxis.	Participants in all cohorts were administered 20 mg/m^2 of Carfilzomib on days +1 and +2, via intravenous catheter (IV) over 30 minutes. Cohort 2: Participants were administered 27 mg/m^2 of Carfilzomib on days +6 and +7. Participants in all cohorts were administered tacrolimus at 0.03 mg/kg continuous infusion over 24 hours, starting on day -3 as standard graft-versus-host disease prophylaxis.	Participants in all cohorts were administered 20 mg/m^2 of Carfilzomib on days +1 and +2, via intravenous catheter (IV) over 30 minutes. Cohort 3: Participants were administered 36 mg/m^2 of Carfilzomib on days +6 and +7. Participants in all cohorts were administered tacrolimus at 0.03 mg/kg continuous infusion over 24 hours, starting on day -3 as standard graft-versus-host disease prophylaxis.	"Participants in all cohorts were administered 20 mg/m^2 of Carfilzomib on days +1 and +2, via intravenous catheter (IV) over 30 minutes. Cohort 4: Participants were administered 45 mg/m^2 of Carfilzomib on days +6 and +7. Participants in all cohorts were administered tacrolimus at 0.03 mg/kg continuous infusion over 24 hours, starting on day -3 as standard graft-versus-host disease prophylaxis.
Period Title: Phase I: Max Dose 20 mg/m^2 (Day 1-7)
STARTED	3	0	0	0
COMPLETED	3	0	0	0
NOT COMPLETED	0	0	0	0
Period Title: Phase I: Max Dose 20 mg/m^2 (Day 1-7)
STARTED	0	3	0	0
COMPLETED	0	3	0	0
NOT COMPLETED	0	0	0	0
Period Title: Phase I: Max Dose 20 mg/m^2 (Day 1-7)
STARTED	0	0	4	0
COMPLETED	0	0	3	0
NOT COMPLETED	0	0	1	0
Period Title: Phase I: Max Dose 20 mg/m^2 (Day 1-7)
STARTED	0	0	0	4
COMPLETED	0	0	0	2
NOT COMPLETED	0	0	0	2
Period Title: Phase I: Max Dose 20 mg/m^2 (Day 1-7)
STARTED	0	0	37	0
COMPLETED	0	0	36	0
NOT COMPLETED	0	0	1	0

Baseline Characteristics

Arm/Group Title	Dose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2	Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2	Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2	Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2	Total
Arm/Group Description	Participants were administered 20 mg/m^2 of Carfilzomib on days 1, 2, 6 and 7.	Participants were administered 20 mg/m^2 on days 1 and 2; 27 mg/m^2 of Carfilzomib on days 6 and 7.	Participants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.	Participants were administered 20 mg/m^2 on days 1 and 2; 45 mg/m^2 of Carfilzomib on days 6 and 7.	Total of all reporting groups
Overall Participants	3	3	41	4	51
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	32	55	58	60	58
Sex: Female, Male (Count of Participants)
Female	1 33.3%	1 33.3%	22 53.7%	0 0%	24 47.1%
Male	2 66.7%	2 66.7%	19 46.3%	4 100%	27 52.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%	0 0%	0 0%
Not Hispanic or Latino	3 100%	3 100%	39 95.1%	4 100%	49 96.1%
Unknown or Not Reported	0 0%	0 0%	2 4.9%	0 0%	2 3.9%

Outcome Measures

1. Primary Outcome

Title	Phase I: Maximum Tolerated Dose (MTD) of Carfilzomib
Description	Subjects were enrolled on the first dose level (20 mg/m^2), following a standard 3+3 dose escalation. For any given dose level, if none of the 3 subjects developed a treatment-related dose limiting toxicity (DLT), defined per protocol, dose escalation would follow. If a DLT occurred in any given dose level, the cohort would be expanded to 6. Further dose escalation would be made only if DLTs occurred in <2 out of 6 subjects. If >=2 of 6 develop DLTs, dose de-escalation would be made to the previous level. The highest dose level at which no more than one of six participants experience a DLT defines the MTD.
Time Frame	Up to day 28

Outcome Measure Data

Analysis Population Description

Phase 1 study participants

Arm/Group Title	Phase 1 Study Participants
Arm/Group Description	Participants in all cohorts were administered 20 mg/m^2 of Carfilzomib on days +1 and +2, via intravenous catheter (IV) over 30 minutes. Dose Level 1, 2, 3, 4: Participants were administered 20, 27, 36, or 45 mg/m^2 of Carfilzomib on days +6 and +7, respectively. Participants in all cohorts were administered tacrolimus at 0.03 mg/kg continuous infusion over 24 hours, starting on day -3 as standard graft-versus-host disease prophylaxis.
Measure Participants	14
Number [milligrams per square meter (mg/m^2)]	36

2. Primary Outcome

Title	Phase II: Kaplan-Meier Estimate of the Percentage of Patients Who Are Alive and Have Not Developed Any "Event"
Description	Kaplan-Meier estimate of the percentage of patients who are alive and have not developed relapse/progression of primary disease or clinical grade III-IV acute graft-versus- host disease (GVHD) or chronic GVHD requiring systemic treatment. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Subjects who have received all 4 doses of carfilzomib at the maximum tolerated dose (MTD) level (dose level 3, 36 mg/m^2): 39 subjects total. Note: three subjects who completed 4 doses of carfilzomib at the MTD during the phase 1 portion of the study were included in phase 2 analysis of the primary outcome measure.

Arm/Group Title	Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IV
Arm/Group Description	Participants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
Measure Participants	39
Number (95% Confidence Interval) [percentage of participants]	31 1033.3%

3. Secondary Outcome

Title	Phase II: Kaplan-Meier Estimate for Progression/Relapse-free Survival Time
Description	Time from day 0 to the date of the first progression/relapse. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Subjects who received all 4 doses of carfilzomib at the maximum tolerated dose (MTD) level (dose level 3, 36 mg/m^2): 39 subjects total. Note: three subjects who completed 4 doses of carfilzomib at the MTD during the phase 1 portion of the study were included in phase 2 analysis.

Arm/Group Title	Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2
Arm/Group Description	Participants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
Measure Participants	39
1 year since transplant	72 2400%
3 years since transplant	40 1333.3%

4. Secondary Outcome

Title	Phase II: Kaplan-Meier Estimate for Overall Survival Time
Description	The time from day 0 to the day of death from any cause. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Subjects who received all 4 doses of carfilzomib at the maximum tolerated dose (MTD) level (dose level 3, 36 mg/m^2): 39 subjects total. Note: three subjects who completed 4 doses of carfilzomib at the MTD during the phase 1 portion of the study were included in phase 2 analysis.

Arm/Group Title	Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2
Arm/Group Description	Participants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
Measure Participants	39
1 year since transplant	72 2400%
3 years since transplant	54 1800%

5. Secondary Outcome

Title	Number of Regimen Related Toxicities (RRTs)
Description	An RTT is defined as an adverse event (AE) that occurs within +37 days after transplant or 30 days after the last dose of carfilzomib (day +7), and is considered to be a direct consequence and a related event as a result of the combination of conditioning chemotherapy, GVHD prophylaxis regimen and carfilzomib.
Time Frame	Up to 30 days post treatment

Outcome Measure Data

Analysis Population Description

Subjects who have received at least one dose of carfilzomib were evaluable for toxicities

Arm/Group Title	Dose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2 IV	Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IV	Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IV	Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV
Arm/Group Description	Participants were administered 20 mg/m^2 of Carfilzomib on days 1, 2, 6 and 7.	Participants were administered 20 mg/m^2 on days 1 and 2; 27 mg/m^2 of Carfilzomib on days 6 and 7.	Participants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.	Participants were administered 20 mg/m^2 on days 1 and 2; 45 mg/m^2 of Carfilzomib on days 6 and 7.
Measure Participants	3	3	41	4
Number [Regimen related toxicities]	4	1	15	6

6. Secondary Outcome

Title	Phase II: Cumulative Incidence of Acute GVHD
Description	The cumulative incidence of acute Graft Versus Host Disease (aGVHD). Events were assigned a severity grade using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4.0; lower values indicate least severe and higher values indicate most severe. Grades 2 - 4 and grades 3 - 4 events are reported. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.
Time Frame	At day 180 post-transplant; data collected up to 3 years

Outcome Measure Data

Analysis Population Description

Subjects who have received all 4 doses of carfilzomib at the maximum tolerated dose (MTD) level (dose level 3, 36 mg/m^2): 39 subjects total. Note: three subjects who completed 4 doses of carfilzomib at the MTD during the phase 1 portion of the study were included in phase 2 analysis of the primary outcome measure.

Arm/Group Title	Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2
Arm/Group Description	Participants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
Measure Participants	39
Acute GVHD grade 2-4	32 1066.7%
Acute GVHD grade 3-4	15 500%

7. Secondary Outcome

Title	Phase II: Cumulative Incidence of Chronic GVHD
Description	The cumulative incidence of chronic Graft Versus Host Disease (GVHD). Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Subjects who received all 4 doses of carfilzomib at the maximum tolerated dose (MTD) level (dose level 3, 36 mg/m^2): 39 subjects total. Note: three subjects who completed 4 doses of carfilzomib at the MTD during the phase 1 portion of the study were included in phase 2 analysis.

Arm/Group Title	Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2
Arm/Group Description	Participants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
Measure Participants	39
cGVHD overall: Day 180	2 66.7%
cGVHD overall: Day 365	15 500%
cGVHD overall: Day 1095	15 500%
cGVHD Moderate / Severe: Day 180	2 66.7%
cGVHD Moderate / Severe: Day 365	10 333.3%
cGVHD Moderate / Severe: Day 1095	10 333.3%
cGVHD Requiring Systemic Therapy: Day 180	2 66.7%
cGVHD Requiring Systemic Therapy: Day 365	7 233.3%
cGVHD Requiring Systemic Therapy: Day 1095	7 233.3%

8. Secondary Outcome

Title	Phase II: Cumulative Incidence of Non-relapse Mortality
Description	The cumulative incidence of non-relapse mortality. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Subjects who received all 4 doses of carfilzomib at the maximum tolerated dose (MTD) level (dose level 3, 36 mg/m^2): 39 subjects total. Note: three subjects who completed 4 doses of carfilzomib at the MTD during the phase 1 portion of the study were included in phase 2 analysis.

Arm/Group Title	Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2
Arm/Group Description	Participants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
Measure Participants	39
Day 180	15 500%
Day 365	17 566.7%
Day 1095	23 766.7%

Adverse Events

Time Frame	Adverse event data were collected up to 100 days after the last dose of carfilzomib. All-cause mortality includes all patients followed for up to three years after their first dose of carfilzomib; total duration of data collection was 6 years with an average duration of 1.8 years.
Arm/Group Title	Dose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2 IV		Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IV		Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IV		Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV
Arm/Group Description	Participants in all cohorts were administered 20 mg/m^2 of Carfilzomib on days +1 and +2, via intravenous catheter (IV) over 30 minutes. Cohort 1: Participants were administered 20 mg/m^2 of Carfilzomib on days +6 and +7.		Participants in all cohorts were administered 20 mg/m^2 of Carfilzomib on days +1 and +2, via intravenous catheter (IV) over 30 minutes. Cohort 2: Participants were administered 27 mg/m^2 of Carfilzomib on days +6 and +7.		Participants in all cohorts were administered 20 mg/m^2 of Carfilzomib on days +1 and +2, via intravenous catheter (IV) over 30 minutes. Cohort 3: Participants were administered 36 mg/m^2 of Carfilzomib on days +6 and +7.		Participants in all cohorts were administered 20 mg/m^2 of Carfilzomib on days +1 and +2, via intravenous catheter (IV) over 30 minutes. Cohort 4: Participants were administered 45 mg/m^2 of Carfilzomib on days +6 and +7.
All Cause Mortality
	Dose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2 IV		Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IV		Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IV		Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		2/3 (66.7%)		18/41 (43.9%)		2/4 (50%)
Serious Adverse Events
	Dose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2 IV		Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IV		Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IV		Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)		2/3 (66.7%)		25/41 (61%)		4/4 (100%)
Blood and lymphatic system disorders
Blood and lymphatic system disorders - Other	0/3 (0%)		0/3 (0%)		4/41 (9.8%)		2/4 (50%)
Febrile neutropenia	0/3 (0%)		1/3 (33.3%)		0/41 (0%)		0/4 (0%)
Cardiac disorders
Atrial fibrillation	0/3 (0%)		1/3 (33.3%)		0/41 (0%)		0/4 (0%)
Eye disorders
Corneal ulcer	0/3 (0%)		0/3 (0%)		0/41 (0%)		1/4 (25%)
Gastrointestinal disorders
Colonic hemorrhage	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Diarrhea	0/3 (0%)		0/3 (0%)		0/41 (0%)		1/4 (25%)
Dysphagia	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Enterocolitis	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Ileus	0/3 (0%)		0/3 (0%)		0/41 (0%)		1/4 (25%)
Lower gastrointestinal hemorrhage	0/3 (0%)		0/3 (0%)		0/41 (0%)		1/4 (25%)
Mucositis oral	0/3 (0%)		1/3 (33.3%)		0/41 (0%)		0/4 (0%)
Nausea	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Small intestinal obstruction	0/3 (0%)		0/3 (0%)		0/41 (0%)		1/4 (25%)
General disorders
Chills	1/3 (33.3%)		0/3 (0%)		0/41 (0%)		0/4 (0%)
Fever	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		1/4 (25%)
Non-cardiac chest pain	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Pain	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Immune system disorders
Anaphylaxis	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Immune system disorders - Other	0/3 (0%)		0/3 (0%)		9/41 (22%)		1/4 (25%)
Infections and infestations
Encephalitis infection	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Infections and infestations - Other	0/3 (0%)		1/3 (33.3%)		4/41 (9.8%)		0/4 (0%)
Lung infection	0/3 (0%)		0/3 (0%)		3/41 (7.3%)		0/4 (0%)
Papulopustular rash	0/3 (0%)		0/3 (0%)		0/41 (0%)		1/4 (25%)
Sepsis	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Upper respiratory infection	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Injury, poisoning and procedural complications
Vascular access complication	0/3 (0%)		1/3 (33.3%)		0/41 (0%)		0/4 (0%)
Investigations
Blood bilirubin increased	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		1/4 (25%)
Metabolism and nutrition disorders
Anorexia	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Dehydration	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Tumor lysis syndrome	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Generalized muscle weakness	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Neck pain	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Pain in extremity	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Nervous system disorders
Encephalopathy	0/3 (0%)		0/3 (0%)		2/41 (4.9%)		0/4 (0%)
Reversible posterior leukoencephalopathy syndrome	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Seizure	0/3 (0%)		0/3 (0%)		2/41 (4.9%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Erythema multiforme	0/3 (0%)		1/3 (33.3%)		0/41 (0%)		0/4 (0%)
Rash maculo-papular	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Vascular disorders
Hypotension	0/3 (0%)		0/3 (0%)		3/41 (7.3%)		0/4 (0%)
Thromboembolic event	0/3 (0%)		1/3 (33.3%)		2/41 (4.9%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Dose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2 IV		Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IV		Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IV		Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100%)		0/3 (0%)		16/41 (39%)		3/4 (75%)
Blood and lymphatic system disorders
Anemia	0/3 (0%)		0/3 (0%)		3/41 (7.3%)		0/4 (0%)
Febrile neutropenia	0/3 (0%)		0/3 (0%)		2/41 (4.9%)		0/4 (0%)
Gastrointestinal disorders
Diarrhea	0/3 (0%)		0/3 (0%)		4/41 (9.8%)		0/4 (0%)
Ileus	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Mucositis oral	3/3 (100%)		0/3 (0%)		5/41 (12.2%)		1/4 (25%)
Nausea	1/3 (33.3%)		0/3 (0%)		3/41 (7.3%)		0/4 (0%)
Vomiting	0/3 (0%)		0/3 (0%)		2/41 (4.9%)		0/4 (0%)
General disorders
Edema limbs	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Fatigue	0/3 (0%)		0/3 (0%)		3/41 (7.3%)		0/4 (0%)
Pain	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Immune system disorders
Immune system disorders - Other	0/3 (0%)		0/3 (0%)		2/41 (4.9%)		0/4 (0%)
Infections and infestations
Enterocolitis infectious	1/3 (33.3%)		0/3 (0%)		0/41 (0%)		0/4 (0%)
Lung infection	1/3 (33.3%)		0/3 (0%)		0/41 (0%)		0/4 (0%)
Papulopustular rash	1/3 (33.3%)		0/3 (0%)		0/41 (0%)		0/4 (0%)
Penile infection	1/3 (33.3%)		0/3 (0%)		0/41 (0%)		0/4 (0%)
Urinary tract infection	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		1/4 (25%)
Investigations
Alanine aminotransferase increased	0/3 (0%)		0/3 (0%)		2/41 (4.9%)		1/4 (25%)
Aspartate aminotransferase increased	0/3 (0%)		0/3 (0%)		5/41 (12.2%)		0/4 (0%)
Blood bilirubin increased	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Creatinine increased	0/3 (0%)		0/3 (0%)		2/41 (4.9%)		1/4 (25%)
Ejection fraction decreased	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Lymphocyte count decreased	0/3 (0%)		0/3 (0%)		3/41 (7.3%)		0/4 (0%)
Neutrophil count decreased	0/3 (0%)		0/3 (0%)		3/41 (7.3%)		0/4 (0%)
Platelet count decreased	0/3 (0%)		0/3 (0%)		3/41 (7.3%)		0/4 (0%)
White blood cell decreased	0/3 (0%)		0/3 (0%)		3/41 (7.3%)		0/4 (0%)
Metabolism and nutrition disorders
Dehydration	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Hypercalcemia	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Hyperglycemia	0/3 (0%)		0/3 (0%)		4/41 (9.8%)		0/4 (0%)
Hyperkalemia	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Hypertriglyceridemia	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Hypocalcemia	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Hypoglycemia	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Hypokalemia	0/3 (0%)		0/3 (0%)		2/41 (4.9%)		0/4 (0%)
Hyponatremia	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		1/4 (25%)
Hypophosphatemia	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Nervous system disorders
Seizure	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		0/4 (0%)
Vascular disorders
Hypertension	0/3 (0%)		0/3 (0%)		4/41 (9.8%)		0/4 (0%)
Hypotension	0/3 (0%)		0/3 (0%)		1/41 (2.4%)		1/4 (25%)

Limitations/Caveats

[Not Specified]

More Information

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.