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Safety Study of the Proteasome Inhibitor PR-171 (Carfilzomib for Injection) in Patients With Hematological Malignancies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00150462
First received: September 6, 2005
Last updated: October 29, 2015
Last verified: October 2015
Results First Received: October 29, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Waldenstrom's Macroglobulinemia
Non-Hodgkin's Lymphoma
Hodgkin's Disease
Multiple Myeloma
Interventions: Drug: Carfilzomib
Drug: Dexamethasone

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Adults with with multiple myeloma (MM)—both secretory and nonsecretory, non-Hodgkin’s lymphoma (NHL), Hodgkin’s disease (HD), or Waldenström’s macroglobulinemia (WM) were eligible for enrollment in this study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study was divided into a sequential Dose Escalation phase (Part 1; Arms 1-9), followed by a Dose Expansion phase (Part 2; Arms 10-11) consisting of a carfilzomib-only cohort and a carfilzomib-plus dexamethasone cohort.

Reporting Groups
  Description
CFZ 1.2 mg/m² Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 2.4 mg/m² Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 4.0 mg/m² Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 6.0 mg/m² Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 8.4 mg/m² Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 11.0 mg/m² Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 15.0 mg/m² Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 20.0 mg/m² Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 27.0 mg/m² Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 20/27 mg/m² Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
CFZ 20/27 mg/m² + DEX Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).

Participant Flow:   Overall Study
    CFZ 1.2 mg/m²     CFZ 2.4 mg/m²     CFZ 4.0 mg/m²     CFZ 6.0 mg/m²     CFZ 8.4 mg/m²     CFZ 11.0 mg/m²     CFZ 15.0 mg/m²     CFZ 20.0 mg/m²     CFZ 27.0 mg/m²     CFZ 20/27 mg/m²     CFZ 20/27 mg/m² + DEX  
STARTED     3     3     4     3     3     4     3     8     6     7     4  
COMPLETED     0 [1]   0 [1]   0 [1]   0 [1]   0 [1]   0 [1]   0 [1]   0 [1]   0 [1]   1 [2]   1 [2]
NOT COMPLETED     3     3     4     3     3     4     3     8     6     6     3  
Disease Progression or Relapse                 3                 1                 2                 1                 2                 2                 3                 5                 5                 3                 2  
Withdrawal by Subject                 0                 1                 1                 0                 1                 2                 0                 1                 0                 1                 0  
Death                 0                 1                 0                 0                 0                 0                 0                 0                 1                 0                 0  
Adverse Event                 0                 0                 0                 1                 0                 0                 0                 2                 0                 1                 0  
Physician Decision                 0                 0                 1                 1                 0                 0                 0                 0                 0                 0                 0  
Other                 0                 0                 0                 0                 0                 0                 0                 0                 0                 1                 1  
[1] Indicates participants remaining on study treatment
[2] Indicates participants who completed 12 cycles of treatment.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
CFZ 1.2 mg/m² Participants received carfilzomib (CFZ) 1.2 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 2.4 mg/m² Participants received carfilzomib 2.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 4.0 mg/m² Participants received carfilzomib 4.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 6.0 mg/m² Participants received carfilzomib 6.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 8.4 mg/m² Participants received carfilzomib 8.4 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 11.0 mg/m² Participants received carfilzomib 11.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 15.0 mg/m² Participants received carfilzomib 15.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 20.0 mg/m² Participants received carfilzomib 20.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 27.0 mg/m² Participants received carfilzomib 27.0 mg/m² administered by intravenous bolus on Days 1, 2, 8, 9, 15 and 16 in 28-day treatment cycles for up to 12 cycles.
CFZ 20/27 mg/m² Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles.
CFZ 20/27 mg/m² + DEX Participants received carfilzomib 20 mg/m² administered by intravenous bolus on Cycle 1 Days 1, 2, 8, 9, 15 and 16, then 27 mg/m² in all subsequent cycles, for up to 12 cycles. Participants also received 20 mg dexamethasone (DEX) administered before each dose of carfilzomib (i.e. 40 mg weekly).
Total Total of all reporting groups

Baseline Measures
    CFZ 1.2 mg/m²     CFZ 2.4 mg/m²     CFZ 4.0 mg/m²     CFZ 6.0 mg/m²     CFZ 8.4 mg/m²     CFZ 11.0 mg/m²     CFZ 15.0 mg/m²     CFZ 20.0 mg/m²     CFZ 27.0 mg/m²     CFZ 20/27 mg/m²     CFZ 20/27 mg/m² + DEX     Total  
Number of Participants  
[units: participants]
  3     3     4     3     3     4     3     8     6     7     4     48  
Age  
[units: years]
Mean (Standard Deviation)
                       
Dose Escalation (Part 1)     62.5  (17.47)     69.6  (4.80)     55.3  (21.71)     51.7  (6.20)     61.6  (9.15)     61.3  (3.76)     50.3  (12.99)     60.6  (11.99)     67.6  (9.82)     NA [1]   NA [1]   60.6  (12.25)  
Dose Expansion (Part 2)     NA [2]   NA [2]   NA [2]   NA [2]   NA [2]   NA [2]   NA [2]   NA [2]   NA [2]   66.3  (9.21)     54.3  (13.57)     61.9  (11.96)  
Gender  
[units: participants]
                       
Female     0     2     3     2     1     4     1     2     2     2     3     22  
Male     3     1     1     1     2     0     2     6     4     5     1     26  
Race/Ethnicity, Customized  
[units: participants]
                       
African American     0     0     0     0     1     0     0     0     0     1     1     3  
Caucasian     3     2     3     3     2     4     3     7     6     6     3     42  
Hispanic     0     1     0     0     0     0     0     0     0     0     0     1  
Native American     0     0     1     0     0     0     0     1     0     0     0     2  
Disease Diagnosis  
[units: participants]
                       
Multiple Myeloma     0     3     0     2     1     2     2     6     5     3     4     28  
Non-Hodgkin's Lymphoma     3     0     3     1     2     2     1     2     1     2     0     17  
Waldenstrom's Macroglobulinemia     0     0     0     0     0     0     0     0     0     2     0     2  
Hodgkin's Disease     0     0     1     0     0     0     0     0     0     0     0     1  
[1] Not applicable for Part 2 groups
[2] Not applicable for Part 1 groups



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Dose-limiting Toxicities (DLTs)   [ Time Frame: 28 days ]

2.  Primary:   Maximum Observed Plasma Concentration of Carfilzomib (Cmax)   [ Time Frame: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose. ]

3.  Primary:   Time to Maximum Observed Plasma Concentration of Carfilzomib (Tmax)   [ Time Frame: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose. ]

4.  Primary:   Area Under the Concentration-time Curve to Last Measureable Timepoint (AUClast) for Carfilzomib   [ Time Frame: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose. ]

5.  Primary:   Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) for Carfilzomib   [ Time Frame: Cycle 1, Day 1 at predose, 5, 15, and 30 minutes, and 1, 2, 4, and 24 hours post dose. ]

6.  Secondary:   Best Clinical Response to Treatment   [ Time Frame: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase. ]

7.  Secondary:   Duration of Response   [ Time Frame: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase. ]

8.  Secondary:   Time to Progression   [ Time Frame: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase. ]

9.  Secondary:   Progression-free Survival   [ Time Frame: From the first dose of study drug until 30 days after the last dose. Median duration of treatment was 6.3 weeks in the dose escalation phase and 6.4 weeks in the dose expansion phase. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen, Inc.
phone: 866-572-6436



Responsible Party: Onyx Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00150462     History of Changes
Other Study ID Numbers: PX-171-002
Study First Received: September 6, 2005
Results First Received: October 29, 2015
Last Updated: October 29, 2015
Health Authority: United States: Food and Drug Administration