Back to resultsA Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects (CHAMPION 2)
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Carfilzomib
Cyclophosphamide
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring multiple myeloma
Eligibility Criteria
Inclusion Criteria:
- Newly diagnosed multiple myeloma
Measurable disease, as defined by 1 or more of the following
- Serum M-protein ≥ 0.5 g/dL, or
- Urine M-protein ≥ 200 mg/24 hours, or
- In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa lambda ( κ/λ) ratio
- Males and females ≥ 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Adequate hepatic function
- Left ventricular ejection fraction (LVEF) ≥ 40%
- Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
- Platelet count ≥ 50 × 10^9/L
- Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min
Exclusion Criteria:
- Planned autologous hematopoietic stem cell transplantation (HSCT) for the initial therapy of newly diagnosed multiple myeloma
- Multiple myeloma of immunoglobulin M (IgM) subtype
- Prior systemic treatment for multiple myeloma
- Glucocorticoid therapy within 14 days prior to enrollment that equals or exceeds the equivalent of dexamethasone 160 mg
- Known amyloidosis
- Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to enrollment.
- Known human immunodeficiency virus (HIV) seropositive, hepatitis C infection, and/or hepatitis B (subjects with hepatitis B surface antigen [SAg] or core antibody receiving and responding to antiviral therapy directed at hepatitis B are allowed)
- Significant neuropathy (Grades ≥ 2) within 14 days prior to enrollment
- Any other clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
Sites / Locations
- California Cancer Associates for Research and Excellence
- James R. Berenson, MD
- The Oncology Institute of Hope and Innovation
- Horizon Oncology Research
- Center for Cancer and Blood Disorders
- Clinical Research Alliance
- Tennessee Oncology
- Texas Oncology
- Virginia Oncology Associates
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Carfilzomib, Cyclophosphamide and Dexamethasone (CCd)
Arm Description
Participants received carfilzomib, cyclophosphamide and dexamethasone for up to eight 28-day cycles, or until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
Outcomes
Primary Outcome Measures
Number of Participants With Dose-limiting Toxicities (DLTs)
The MTD is defined as the highest carfilzomib dose at which fewer than 33% of participants experience a treatment-related dose-limiting toxicity (DLT) during the first 28-day cycle. The number of participants who experienced a DLT is reported.
Dose-limiting toxicities are defined as any of the following carfilzomib-related adverse events:
Nonhematologic:
≥ Grade 3 non-hematological toxicity
≥ Grade 3 acute kidney injury (creatinine > 3 × baseline or > 4.0 mg/dL) lasting > 72 hours
Hematologic:
Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10^9/L) lasting for > 7 days
Febrile neutropenia (ANC < 1.0 × 10^9/L with a fever ≥ 38.3ºC) of any duration
Grade 4 thrombocytopenia (< 25 × 10^9/L) that persists for > 14 days, despite holding treatment
Grade 3 or 4 thrombocytopenia associated with > Grade 1 bleeding
Secondary Outcome Measures
Overall Response Rate (ORR)
Participants were evaluated for disease response and progression by the investigator according to the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). Disease response and progression assessments included serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum immunofixation, serum free light chain (SFLC), bone marrow sample (including fluorescent in situ hybridization [FISH]), plasmacytoma evaluation, and skeletal survey. Overall response rate is defined as the percentage of participants with a best response of stringent complete response, complete response, very good partial response (VGPR), or partial response.
Time To Response (TTR)
Time to response is defined as months from treatment start to first documentation of response of partial response or better. Summary of time to response includes confirmed responders of PR or better only.
Number of Participants With Adverse Events
Adverse events (AEs) were graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 and using the following scale:
Grade 1 = Mild, Grade 3 = Moderate; Grade 3 = Severe, Grade 4 = Life-threatening; Grade 5 = Fatal.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01980589
Brief Title
A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects
Acronym
CHAMPION 2
Official Title
A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective was to determine the maximum tolerated dose of carfilzomib given twice weekly in combination with cyclophosphamide and dexamethasone for patients with newly diagnosed multiple myeloma.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
Keywords
multiple myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carfilzomib, Cyclophosphamide and Dexamethasone (CCd)
Arm Type
Experimental
Arm Description
Participants received carfilzomib, cyclophosphamide and dexamethasone for up to eight 28-day cycles, or until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death.
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
PR-171, PR171, Kyprolis® (carfilzomib) for Injection
Intervention Description
Carfilzomib administered as a 30-minute intravenous (IV) infusion on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle. On Days 1 and 2 of Cycle 1, all participants received carfilzomib at 20 mg/m².
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide administered orally (PO) at the dose of 300 mg/m² on Days 1, 8, and 15 of each 28-day cycle.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone administered PO or IV at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle.
Primary Outcome Measure Information:
Title
Number of Participants With Dose-limiting Toxicities (DLTs)
Description
The MTD is defined as the highest carfilzomib dose at which fewer than 33% of participants experience a treatment-related dose-limiting toxicity (DLT) during the first 28-day cycle. The number of participants who experienced a DLT is reported.
Dose-limiting toxicities are defined as any of the following carfilzomib-related adverse events:
Nonhematologic:
≥ Grade 3 non-hematological toxicity
≥ Grade 3 acute kidney injury (creatinine > 3 × baseline or > 4.0 mg/dL) lasting > 72 hours
Hematologic:
Grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10^9/L) lasting for > 7 days
Febrile neutropenia (ANC < 1.0 × 10^9/L with a fever ≥ 38.3ºC) of any duration
Grade 4 thrombocytopenia (< 25 × 10^9/L) that persists for > 14 days, despite holding treatment
Grade 3 or 4 thrombocytopenia associated with > Grade 1 bleeding
Time Frame
First cycle treatment over 28-days
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
Participants were evaluated for disease response and progression by the investigator according to the International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). Disease response and progression assessments included serum protein electrophoresis (SPEP), urine protein electrophoresis (UPEP), serum immunofixation, serum free light chain (SFLC), bone marrow sample (including fluorescent in situ hybridization [FISH]), plasmacytoma evaluation, and skeletal survey. Overall response rate is defined as the percentage of participants with a best response of stringent complete response, complete response, very good partial response (VGPR), or partial response.
Time Frame
Disease response was assessed at the end of each cycle and 30 days after the last treatment; maximum treatment duration was 32 weeks.
Title
Time To Response (TTR)
Description
Time to response is defined as months from treatment start to first documentation of response of partial response or better. Summary of time to response includes confirmed responders of PR or better only.
Time Frame
Disease response was assessed at the end of each cycle and 30 days after the last treatment; maximum treatment duration was 32 weeks.
Title
Number of Participants With Adverse Events
Description
Adverse events (AEs) were graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03 and using the following scale:
Grade 1 = Mild, Grade 3 = Moderate; Grade 3 = Severe, Grade 4 = Life-threatening; Grade 5 = Fatal.
Time Frame
From first dose of study drug until 30 days after last dose; median duration of treatment was 31 weeks.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Newly diagnosed multiple myeloma
Measurable disease, as defined by 1 or more of the following
Serum M-protein ≥ 0.5 g/dL, or
Urine M-protein ≥ 200 mg/24 hours, or
In subjects without detectable serum or urine M-protein, serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa lambda ( κ/λ) ratio
Males and females ≥ 18 years of age
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Adequate hepatic function
Left ventricular ejection fraction (LVEF) ≥ 40%
Absolute neutrophil count (ANC) ≥ 1.0 × 10^9/L
Platelet count ≥ 50 × 10^9/L
Calculated or measured creatinine clearance (CrCl) of ≥ 15 mL/min
Exclusion Criteria:
Planned autologous hematopoietic stem cell transplantation (HSCT) for the initial therapy of newly diagnosed multiple myeloma
Multiple myeloma of immunoglobulin M (IgM) subtype
Prior systemic treatment for multiple myeloma
Glucocorticoid therapy within 14 days prior to enrollment that equals or exceeds the equivalent of dexamethasone 160 mg
Known amyloidosis
Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to enrollment.
Known human immunodeficiency virus (HIV) seropositive, hepatitis C infection, and/or hepatitis B (subjects with hepatitis B surface antigen [SAg] or core antibody receiving and responding to antiviral therapy directed at hepatitis B are allowed)
Significant neuropathy (Grades ≥ 2) within 14 days prior to enrollment
Any other clinically significant medical disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
California Cancer Associates for Research and Excellence
City
Encinitas
State/Province
California
Country
United States
Facility Name
James R. Berenson, MD
City
West Hollywood
State/Province
California
Country
United States
Facility Name
The Oncology Institute of Hope and Innovation
City
Whittier
State/Province
California
Country
United States
Facility Name
Horizon Oncology Research
City
Lafayette
State/Province
Indiana
Country
United States
Facility Name
Center for Cancer and Blood Disorders
City
Bethesda
State/Province
Maryland
Country
United States
Facility Name
Clinical Research Alliance
City
New York
State/Province
New York
Country
United States
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Texas Oncology
City
Austin
State/Province
Texas
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
Country
United States
12. IPD Sharing Statement
Learn more about this trial
A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects
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