A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects (CHAMPION 2)
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| ClinicalTrials.gov Identifier: NCT01980589 |
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Recruitment Status :
Completed
First Posted : November 11, 2013
Results First Posted : October 31, 2016
Last Update Posted : May 30, 2017
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Sponsor:
Amgen
Information provided by (Responsible Party):
Amgen
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Multiple Myeloma | Drug: Carfilzomib Drug: Cyclophosphamide Drug: Dexamethasone | Phase 1 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 22 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | A Multicenter, Open-label, Phase 1b Study of Carfilzomib, Cyclophosphamide and Dexamethasone in Newly Diagnosed Multiple Myeloma Subjects |
| Study Start Date : | August 2013 |
| Actual Primary Completion Date : | March 2016 |
| Actual Study Completion Date : | March 2016 |
Resource links provided by the National Library of Medicine
MedlinePlus Genetics related topics:
Multiple myeloma
MedlinePlus related topics:
Multiple Myeloma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Carfilzomib, Cyclophosphamide and Dexamethasone (CCd)
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.
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Drug: Carfilzomib
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.
Other Names:
Drug: Cyclophosphamide Cyclophosphamide administered orally (PO) at the dose of 300 mg/m² on Days 1, 8, and 15 of each 28-day cycle. Drug: Dexamethasone Dexamethasone administered PO or IV at 40 mg on Days 1, 8, 15, and 22 of each 28-day cycle. |
Primary Outcome Measures :
- Number of Participants With Dose-limiting Toxicities (DLTs) [ Time Frame: First cycle treatment over 28-days ]
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) [ 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. ]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 Frame: Disease response was assessed at the end of each cycle and 30 days after the last treatment; maximum treatment duration was 32 weeks. ]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 [ Time Frame: From first dose of study drug until 30 days after last dose; median duration of treatment was 31 weeks. ]
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.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Newly diagnosed multiple myeloma
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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
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01980589
Locations
| United States, California | |
| California Cancer Associates for Research and Excellence | |
| Encinitas, California, United States | |
| James R. Berenson, MD | |
| West Hollywood, California, United States | |
| The Oncology Institute of Hope and Innovation | |
| Whittier, California, United States | |
| United States, Indiana | |
| Horizon Oncology Research | |
| Lafayette, Indiana, United States | |
| United States, Maryland | |
| Center for Cancer and Blood Disorders | |
| Bethesda, Maryland, United States | |
| United States, New York | |
| Clinical Research Alliance | |
| New York, New York, United States | |
| United States, Tennessee | |
| Tennessee Oncology | |
| Nashville, Tennessee, United States | |
| United States, Texas | |
| Texas Oncology | |
| Austin, Texas, United States | |
| United States, Virginia | |
| Virginia Oncology Associates | |
| Norfolk, Virginia, United States | |
Sponsors and Collaborators
Amgen
Investigators
| Study Director: | MD | Amgen |
| Responsible Party: | Amgen |
| ClinicalTrials.gov Identifier: | NCT01980589 |
| Other Study ID Numbers: |
2012-003 |
| First Posted: | November 11, 2013 Key Record Dates |
| Results First Posted: | October 31, 2016 |
| Last Update Posted: | May 30, 2017 |
| Last Verified: | April 2017 |
Keywords provided by Amgen:
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multiple myeloma |
Additional relevant MeSH terms:
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Multiple Myeloma Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Dexamethasone |
Cyclophosphamide Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents Gastrointestinal Agents |