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)
53
Enrollment
1
Location
1
Arm
72.5
Actual Duration (Months)
0.7
Patients Per Site Per Month

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 DiseaseIntervention/TreatmentPhase
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

ArmIntervention/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

    SiteCityStateCountryPostal Code
    1University of Michigan HospitalAnn ArborMichiganUnited States48109

    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)

    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

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment DetailTwo patients who consented never began treatment.
    Arm/Group TitleDose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2
    Arm/Group DescriptionParticipants 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)
    STARTED3000
    COMPLETED3000
    NOT COMPLETED0000
    Period Title: Phase I: Max Dose 20 mg/m^2 (Day 1-7)
    STARTED0300
    COMPLETED0300
    NOT COMPLETED0000
    Period Title: Phase I: Max Dose 20 mg/m^2 (Day 1-7)
    STARTED0040
    COMPLETED0030
    NOT COMPLETED0010
    Period Title: Phase I: Max Dose 20 mg/m^2 (Day 1-7)
    STARTED0004
    COMPLETED0002
    NOT COMPLETED0002
    Period Title: Phase I: Max Dose 20 mg/m^2 (Day 1-7)
    STARTED00370
    COMPLETED00360
    NOT COMPLETED0010

    Baseline Characteristics

    Arm/Group TitleDose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2Total
    Arm/Group DescriptionParticipants 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 Participants3341451
    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
    TitlePhase I: Maximum Tolerated Dose (MTD) of Carfilzomib
    DescriptionSubjects 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 FrameUp to day 28

    Outcome Measure Data

    Analysis Population Description
    Phase 1 study participants
    Arm/Group TitlePhase 1 Study Participants
    Arm/Group DescriptionParticipants 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 Participants14
    Number [milligrams per square meter (mg/m^2)]
    36
    2. Primary Outcome
    TitlePhase II: Kaplan-Meier Estimate of the Percentage of Patients Who Are Alive and Have Not Developed Any "Event"
    DescriptionKaplan-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 Frame1 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 TitleDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IV
    Arm/Group DescriptionParticipants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
    Measure Participants39
    Number (95% Confidence Interval) [percentage of participants]
    31
    1033.3%
    3. Secondary Outcome
    TitlePhase II: Kaplan-Meier Estimate for Progression/Relapse-free Survival Time
    DescriptionTime 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 FrameUp 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 TitleDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2
    Arm/Group DescriptionParticipants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
    Measure Participants39
    1 year since transplant
    72
    2400%
    3 years since transplant
    40
    1333.3%
    4. Secondary Outcome
    TitlePhase II: Kaplan-Meier Estimate for Overall Survival Time
    DescriptionThe 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 FrameUp 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 TitleDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2
    Arm/Group DescriptionParticipants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
    Measure Participants39
    1 year since transplant
    72
    2400%
    3 years since transplant
    54
    1800%
    5. Secondary Outcome
    TitleNumber of Regimen Related Toxicities (RRTs)
    DescriptionAn 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 FrameUp 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 TitleDose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2 IVDose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IVDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IVDose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV
    Arm/Group DescriptionParticipants 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 Participants33414
    Number [Regimen related toxicities]
    4
    1
    15
    6
    6. Secondary Outcome
    TitlePhase II: Cumulative Incidence of Acute GVHD
    DescriptionThe 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 FrameAt 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 TitleDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2
    Arm/Group DescriptionParticipants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
    Measure Participants39
    Acute GVHD grade 2-4
    32
    1066.7%
    Acute GVHD grade 3-4
    15
    500%
    7. Secondary Outcome
    TitlePhase II: Cumulative Incidence of Chronic GVHD
    DescriptionThe 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 FrameUp 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 TitleDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2
    Arm/Group DescriptionParticipants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
    Measure Participants39
    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
    TitlePhase II: Cumulative Incidence of Non-relapse Mortality
    DescriptionThe 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 FrameUp 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 TitleDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2
    Arm/Group DescriptionParticipants were administered 20 mg/m^2 on days 1 and 2; 36 mg/m^2 of Carfilzomib on days 6 and 7.
    Measure Participants39
    Day 180
    15
    500%
    Day 365
    17
    566.7%
    Day 1095
    23
    766.7%

    Adverse Events

    Time FrameAdverse 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.
    Adverse Event Reporting Description
    Arm/Group TitleDose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2 IVDose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IVDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IVDose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV
    Arm/Group DescriptionParticipants 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 IVDose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IVDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IVDose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/3 (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 IVDose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IVDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IVDose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total1/3 (33.3%) 2/3 (66.7%) 25/41 (61%) 4/4 (100%)
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders - Other0/3 (0%) 0/3 (0%) 4/41 (9.8%) 2/4 (50%)
    Febrile neutropenia0/3 (0%) 1/3 (33.3%) 0/41 (0%) 0/4 (0%)
    Cardiac disorders
    Atrial fibrillation0/3 (0%) 1/3 (33.3%) 0/41 (0%) 0/4 (0%)
    Eye disorders
    Corneal ulcer0/3 (0%) 0/3 (0%) 0/41 (0%) 1/4 (25%)
    Gastrointestinal disorders
    Colonic hemorrhage0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Diarrhea0/3 (0%) 0/3 (0%) 0/41 (0%) 1/4 (25%)
    Dysphagia0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Enterocolitis0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Ileus0/3 (0%) 0/3 (0%) 0/41 (0%) 1/4 (25%)
    Lower gastrointestinal hemorrhage0/3 (0%) 0/3 (0%) 0/41 (0%) 1/4 (25%)
    Mucositis oral0/3 (0%) 1/3 (33.3%) 0/41 (0%) 0/4 (0%)
    Nausea0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Small intestinal obstruction0/3 (0%) 0/3 (0%) 0/41 (0%) 1/4 (25%)
    General disorders
    Chills1/3 (33.3%) 0/3 (0%) 0/41 (0%) 0/4 (0%)
    Fever0/3 (0%) 0/3 (0%) 1/41 (2.4%) 1/4 (25%)
    Non-cardiac chest pain0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Pain0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Immune system disorders
    Anaphylaxis0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Immune system disorders - Other0/3 (0%) 0/3 (0%) 9/41 (22%) 1/4 (25%)
    Infections and infestations
    Encephalitis infection0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Infections and infestations - Other0/3 (0%) 1/3 (33.3%) 4/41 (9.8%) 0/4 (0%)
    Lung infection0/3 (0%) 0/3 (0%) 3/41 (7.3%) 0/4 (0%)
    Papulopustular rash0/3 (0%) 0/3 (0%) 0/41 (0%) 1/4 (25%)
    Sepsis0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Upper respiratory infection0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Injury, poisoning and procedural complications
    Vascular access complication0/3 (0%) 1/3 (33.3%) 0/41 (0%) 0/4 (0%)
    Investigations
    Blood bilirubin increased0/3 (0%) 0/3 (0%) 1/41 (2.4%) 1/4 (25%)
    Metabolism and nutrition disorders
    Anorexia0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Dehydration0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Tumor lysis syndrome0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Musculoskeletal and connective tissue disorders
    Generalized muscle weakness0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Neck pain0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Pain in extremity0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Nervous system disorders
    Encephalopathy0/3 (0%) 0/3 (0%) 2/41 (4.9%) 0/4 (0%)
    Reversible posterior leukoencephalopathy syndrome0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Seizure0/3 (0%) 0/3 (0%) 2/41 (4.9%) 0/4 (0%)
    Skin and subcutaneous tissue disorders
    Erythema multiforme0/3 (0%) 1/3 (33.3%) 0/41 (0%) 0/4 (0%)
    Rash maculo-papular0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Vascular disorders
    Hypotension0/3 (0%) 0/3 (0%) 3/41 (7.3%) 0/4 (0%)
    Thromboembolic event0/3 (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 IVDose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IVDose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IVDose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/3 (100%) 0/3 (0%) 16/41 (39%) 3/4 (75%)
    Blood and lymphatic system disorders
    Anemia0/3 (0%) 0/3 (0%) 3/41 (7.3%) 0/4 (0%)
    Febrile neutropenia0/3 (0%) 0/3 (0%) 2/41 (4.9%) 0/4 (0%)
    Gastrointestinal disorders
    Diarrhea0/3 (0%) 0/3 (0%) 4/41 (9.8%) 0/4 (0%)
    Ileus0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Mucositis oral3/3 (100%) 0/3 (0%) 5/41 (12.2%) 1/4 (25%)
    Nausea1/3 (33.3%) 0/3 (0%) 3/41 (7.3%) 0/4 (0%)
    Vomiting0/3 (0%) 0/3 (0%) 2/41 (4.9%) 0/4 (0%)
    General disorders
    Edema limbs0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Fatigue0/3 (0%) 0/3 (0%) 3/41 (7.3%) 0/4 (0%)
    Pain0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Immune system disorders
    Immune system disorders - Other0/3 (0%) 0/3 (0%) 2/41 (4.9%) 0/4 (0%)
    Infections and infestations
    Enterocolitis infectious1/3 (33.3%) 0/3 (0%) 0/41 (0%) 0/4 (0%)
    Lung infection1/3 (33.3%) 0/3 (0%) 0/41 (0%) 0/4 (0%)
    Papulopustular rash1/3 (33.3%) 0/3 (0%) 0/41 (0%) 0/4 (0%)
    Penile infection1/3 (33.3%) 0/3 (0%) 0/41 (0%) 0/4 (0%)
    Urinary tract infection0/3 (0%) 0/3 (0%) 1/41 (2.4%) 1/4 (25%)
    Investigations
    Alanine aminotransferase increased0/3 (0%) 0/3 (0%) 2/41 (4.9%) 1/4 (25%)
    Aspartate aminotransferase increased0/3 (0%) 0/3 (0%) 5/41 (12.2%) 0/4 (0%)
    Blood bilirubin increased0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Creatinine increased0/3 (0%) 0/3 (0%) 2/41 (4.9%) 1/4 (25%)
    Ejection fraction decreased0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Lymphocyte count decreased0/3 (0%) 0/3 (0%) 3/41 (7.3%) 0/4 (0%)
    Neutrophil count decreased0/3 (0%) 0/3 (0%) 3/41 (7.3%) 0/4 (0%)
    Platelet count decreased0/3 (0%) 0/3 (0%) 3/41 (7.3%) 0/4 (0%)
    White blood cell decreased0/3 (0%) 0/3 (0%) 3/41 (7.3%) 0/4 (0%)
    Metabolism and nutrition disorders
    Dehydration0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Hypercalcemia0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Hyperglycemia0/3 (0%) 0/3 (0%) 4/41 (9.8%) 0/4 (0%)
    Hyperkalemia0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Hypertriglyceridemia0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Hypocalcemia0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Hypoglycemia0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Hypokalemia0/3 (0%) 0/3 (0%) 2/41 (4.9%) 0/4 (0%)
    Hyponatremia0/3 (0%) 0/3 (0%) 1/41 (2.4%) 1/4 (25%)
    Hypophosphatemia0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Musculoskeletal and connective tissue disorders
    Back pain0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Nervous system disorders
    Seizure0/3 (0%) 0/3 (0%) 1/41 (2.4%) 0/4 (0%)
    Vascular disorders
    Hypertension0/3 (0%) 0/3 (0%) 4/41 (9.8%) 0/4 (0%)
    Hypotension0/3 (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.

    Results Point of Contact

    Name/TitleAttaphol Pawarode, M.D.
    OrganizationUniversity of Michigan Rogel Cancer Center
    Phone734-936-8785
    Emailpawarode@med.umich.edu
    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