Back to resultsA Study of Weekly Carfilzomib in Combination With Dexamethasone for Progressive Multiple Myeloma (CHAMPION 1)
Primary Purpose
Multiple Myeloma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Carfilzomib
Dexamethasone
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Multiple myeloma with relapsing or progressive disease at study entry
Measurable disease, as defined by 1 or more of the following (assessed within 21 days prior to enrollment):
- Serum M-protein ≥ 0.5 g/dL, or
- Urine M-protein ≥ 200 mg/24 hours, or
- Only in patients who do not meet a or b, then use serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa/lambda ratio
- Prior treatment with 1 to 3 prior regimens for multiple myeloma for Phase 1 and Phase 2 (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy
- Age ≥ 18 years
- Life expectancy ≥ 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Adequate hepatic function within 21 days prior to enrollment, with bilirubin < 1.5 × the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 × ULN
- Left ventricular ejection fraction (LVEF) ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated acquisition scan (MUGA) is acceptable if ECHO is not available
- Absolute neutrophil count (ANC) ≥ 1000/mm³ within 21 days prior to enrollment. Screening ANC is to be independent of growth factor support for ≥ 1 week
- Hemoglobin ≥ 8.0 g/dL within 21 days prior to enrollment. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion must have been at least 7 days prior to obtaining screening hemoglobin
- Platelet count ≥ 50,000/mm³ (≥ 30,000/mm³ if myeloma involvement in the bone marrow is > 50%) within 21 days prior to enrollment. Patients must not have received platelet transfusions for at least 7 days prior to obtaining the screening platelet count
- Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min within 21 days prior to enrollment. Calculation based on standard formula, such as the Cockcroft and Gault: [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female
- Written informed consent in accordance with federal, local, and institutional guidelines
- Female patients of childbearing potential (FCBP) must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use an effective method of contraception during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations). Postmenopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test
- Male patients must agree to use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with an FCBP
Exclusion Criteria:
- Multiple myeloma of Immunoglobulin M (IgM) subtype
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
- Waldenström's macroglobulinemia
- Amyloidosis
- Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to enrollment
- Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to enrollment
- Treatment with bortezomib (Velcade®), thalidomide (Thalomid®) or lenalidomide (Revlimid®) within 21 days prior to enrollment
- Focal radiation therapy within 7 days prior to enrollment. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (ie, prior radiation must have been to < 30% of the bone marrow)
- Immunotherapy within 21 days prior to enrollment
- Major surgery within 21 days prior to enrollment
- Active congestive heart failure (New York Heart Association [NYHA] Classes III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to enrollment
- Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B virus [HBV]), or antifungal agents within 14 days prior to enrollment
- Known human immunodeficiency virus (HIV) seropositivity
- Known hepatitis B or C virus infection (except for patients with HBV who are receiving and responding to HBV antiviral therapy: these patients are allowed)
- Patients with known cirrhosis
Second malignancy within the past 3 years, except:
- Adequately treated basal cell or squamous cell skin cancer
- Carcinoma in situ of the cervix
- Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
- Breast carcinoma in situ with full surgical resection
- Treated medullary or papillary thyroid cancer
- Patients with myelodysplastic syndrome
- Significant neuropathy (Grades 3 to 4) within 14 days prior to enrollment
- Female patients who are pregnant or lactating
- Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
- Prior carfilzomib treatment
- Prior participation in any Onyx-sponsored Phase 3 trial
- Patients with contraindication to dexamethasone
- Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
- Ongoing graft-versus-host disease
- Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment
- Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment
- Any other clinically significant medical disease or psychiatric condition that, in the Investigator's opinion, may interfere with protocol adherence or a patient's ability to give informed consent
Sites / Locations
- Arizona Oncology Associates
- Comprehensive Blood and Cancer Center (CCBC)
- California Cancer Associates for Research and Excellence
- Robert A. Moss, M.D., FACP, Inc.
- California Cancer Associates for Research and Excellence
- Cedars-Sinai Medical Center
- Monterey Bay Oncology
- Sansum Clinic
- Central Coast Medical Oncology Corporation
- James R. Berenson M.D. Inc.
- The Oncology Insititute of Hope and Innovation
- Rocky Mountain Cancer Centers
- Florida Cancer Specialists - South
- Florida Cancer Specialists - North
- Illinois Cancer Care
- Illinois Cancer Specialists
- Illinois Cancer Specialists
- Fort Wayne Oncology & Hematology
- Horizon Oncology Research, Inc.
- Center for Cancer and Blood Disorders (CCBD)
- Hematology-Oncology Associates of Northern NJ, PA
- New Mexico Cancer Care Alliance
- Clinical Research Alliance
- Hudson Valley Hematology Oncology Associates
- Willamette Valley Cancer Institute and Research Center
- Tennessee Oncology, PLLC
- St. Joseph Regional Cancer Center
- Millennium Oncology
- Waldron Medical Research and Development Center
- Cancer Care Centers of South Texas
- Center at Cancer Therapy & Research Center at The University of Texas Health Science Center at San Antonio
- Blood and Cancer Center of East Texas
- Shenandoah Oncology, PC
- Northwest Cancer Specialists
- Yakima Valley Memorial Hospital/ North Star Lodge
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Carfilzomib
Arm Description
In phase 1 participants were assigned to one of four sequential dose-escalating cohorts to receive 45, 56, 70 or 88 mg/m² carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15. In phase 2 participants received carfilzomib at the maximum tolerated dose (MTD) established in the Phase 1 portion of the study on days 1, 8 and 15 plus 40 mg dexamethasone IV or orally at the same schedule as used in the Phase 1 portion of the study. Participants were treated until confirmed progressive disease, unacceptable toxicity, withdrew consent for further treatment, were lost to follow-up, died, or the sponsor closed the study.
Outcomes
Primary Outcome Measures
Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
The MTD was defined as the highest carfilzomib dose at which < 33% of participants had a treatment-related DLT during the first 28-day cycle. A DLT was categorized as nonhematologic or hematologic and defined as follows:
Nonhematologic:
≥ grade 3 nonhematological toxicity (excluding nausea, vomiting, diarrhea, fatigue lasting < 14 days, increased serum creatinine or electrolyte abnormalities not clinically significant or requiring treatment)
≥ grade 3 acute kidney injury (creatinine > 3 x baseline or > 4.0 mg/dL) lasting > 72 hours
≥ grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy
Hematologic:
grade 4 neutropenia (absolute neutrophil count [ANC] < 500/mm³) for > 7 days
febrile neutropenia (ANC < 1000/mm³ with a fever ≥ 38.3ºC) of any duration
grade 4 thrombocytopenia (< 25 000/mm³) for > 14 days, despite holding treatment
grade 3 or 4 thrombocytopenia (< lower limit of normal) associated with > grade 1 bleeding
Overall Response Rate (ORR)
Disease response was evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). ORR was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).
sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).
CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in BM.
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein <100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to < 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
Secondary Outcome Measures
Clinical Benefit Response Rate
Clinical benefit rate was defined as the percentage of participants whose best response was sCR, CR, VGPR, PR, or minimal response (MR), where MR is defined by the European Group for Blood and Marrow Transplant (EBMT) criteria as a 25% to 49% reduction in the level of serum M-protein or a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour, maintained for a minimum of 8 weeks.
Progression-free Survival
Progression-free survival (PFS) was defined as the time from first dose to the earlier of disease progression or death due to any cause. The duration of PFS was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.
Participants were evaluated for disease response and progression by the investigator according to the IMWG-URC.
Time To Progression
Time to progression (TTP) was defined as the time from first dose to disease progression evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). TTP was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.
Duration of Response
Duration of response (DOR) was defined as the time from first evidence of PR or better to disease progression or death due to any cause. DOR was calculated using Kaplan-Meier methods; Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.
Number of Participants With Adverse Events
Adverse events were graded using National Cancer Institute-Common Terminology Criteria for Adverse Events (version 4.03).
Time to Maximum Plasma Concentration of Carfilzomib
Maximum Plasma Concentration of Carfilzomib
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Carfilzomib
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) fo Carfilzomib
Area Under the Plasma Concentration-time Curve During the Dosing Interval (0-168 Hours) for Carfilzomib
Volume of Distribution Observed at Steady State (Vss) for Carfilzomib
Terminal Half-life (T1/2,z) for Carfilzomib
Clearance of Carfilzomib After IV Infusion
Mean Residence Time Observed From Time Zero to Infinity (MRT0-∞) for Carfilzomib
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01677858
Brief Title
A Study of Weekly Carfilzomib in Combination With Dexamethasone for Progressive Multiple Myeloma
Acronym
CHAMPION 1
Official Title
A Phase 1/2 Study of Weekly Carfilzomib in Combination With Dexamethasone for Progressive Multiple Myeloma
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
July 4, 2012 (undefined)
Primary Completion Date
July 22, 2016 (Actual)
Study Completion Date
October 31, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The study had the following primary objectives:
Phase 1: to determine the maximum tolerated dose (MTD) of once-weekly (QW) carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior therapies
Phase 2: to estimate the overall response rate (ORR) for patients with relapsed or refractory multiple myeloma who received 1 to 3 prior therapies treated with carfilzomib and dexamethasone QW at the MTD established in phase 1.
Detailed Description
This is a Phase 1/2, multicenter, single-arm, nonrandomized, open-label and dose-escalation study of weekly carfilzomib and dexamethasone for patients with progressive multiple myeloma. The Phase 1 dose escalation portion will enroll patients into sequential dose-escalating cohorts consisting of 3 patients each to establish the maximum tolerated dose (MTD) of carfilzomib administered weekly as a 30 minute intravenous (IV) infusion with dexamethasone. The Phase 2 portion will enroll patients using the MTD established for carfilzomib from the Phase 1 portion of the study. Dexamethasone will be administered IV or orally at the same dose and schedule as used in the Phase 1 portion of the study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
116 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Carfilzomib
Arm Type
Experimental
Arm Description
In phase 1 participants were assigned to one of four sequential dose-escalating cohorts to receive 45, 56, 70 or 88 mg/m² carfilzomib administered by intravenous (IV) infusion on days 1, 8 and 15 of each 28-day cycle. Participants also received 40 mg dexamethasone IV or orally on days 1, 8, 15 and 22 for the first 8 cycles; starting with cycle 9, dexamethasone was administered only on days 1, 8, and 15.
In phase 2 participants received carfilzomib at the maximum tolerated dose (MTD) established in the Phase 1 portion of the study on days 1, 8 and 15 plus 40 mg dexamethasone IV or orally at the same schedule as used in the Phase 1 portion of the study.
Participants were treated until confirmed progressive disease, unacceptable toxicity, withdrew consent for further treatment, were lost to follow-up, died, or the sponsor closed the study.
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
Krypolis
Intervention Description
Carfilzomib was administered as a 30-minute IV infusion on days 1, 8, and 15 of each 28-day treatment cycle.
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Intervention Description
Dexamethasone was administered at a dose of 40 mg IV or orally (PO) on days 1, 8, 15, and 22 for the first 8 cycles; starting with cycle 9 dexamethasone was administered on days 1, 8, and 15.
Primary Outcome Measure Information:
Title
Phase 1: Number of Participants With Dose-limiting Toxicities (DLTs)
Description
The MTD was defined as the highest carfilzomib dose at which < 33% of participants had a treatment-related DLT during the first 28-day cycle. A DLT was categorized as nonhematologic or hematologic and defined as follows:
Nonhematologic:
≥ grade 3 nonhematological toxicity (excluding nausea, vomiting, diarrhea, fatigue lasting < 14 days, increased serum creatinine or electrolyte abnormalities not clinically significant or requiring treatment)
≥ grade 3 acute kidney injury (creatinine > 3 x baseline or > 4.0 mg/dL) lasting > 72 hours
≥ grade 3 nausea, vomiting, or diarrhea uncontrolled by maximal antiemetic/antidiarrheal therapy
Hematologic:
grade 4 neutropenia (absolute neutrophil count [ANC] < 500/mm³) for > 7 days
febrile neutropenia (ANC < 1000/mm³ with a fever ≥ 38.3ºC) of any duration
grade 4 thrombocytopenia (< 25 000/mm³) for > 14 days, despite holding treatment
grade 3 or 4 thrombocytopenia (< lower limit of normal) associated with > grade 1 bleeding
Time Frame
28 days
Title
Overall Response Rate (ORR)
Description
Disease response was evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). ORR was defined as the percentage of participants with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR).
sCR: As for CR, normal serum free light chain (SFLC) ratio and no clonal cells in bone marrow (BM).
CR: No immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas and < 5% plasma cells in BM.
VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% reduction in serum M-protein with urine M-protein <100 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
PR: ≥ 50% reduction of serum M-protein and reduction in urine M-protein by ≥ 90% or to < 200 mg/24 hours. A ≥ 50% reduction in the size of soft tissue plasmacytomas if present at baseline.
Time Frame
Disease response was assessed once every treatment cycle (28 days) and 30 days after last dose; the median overall treatment duration was 33.6 weeks.
Secondary Outcome Measure Information:
Title
Clinical Benefit Response Rate
Description
Clinical benefit rate was defined as the percentage of participants whose best response was sCR, CR, VGPR, PR, or minimal response (MR), where MR is defined by the European Group for Blood and Marrow Transplant (EBMT) criteria as a 25% to 49% reduction in the level of serum M-protein or a 50% to 89% reduction in 24-hour urinary M-protein, which still exceeds 200 mg /24 hour, maintained for a minimum of 8 weeks.
Time Frame
Disease response was assessed once every treatment cycle (28 days) and 30 days after last dose; the median overall treatment duration was 33.6 weeks.
Title
Progression-free Survival
Description
Progression-free survival (PFS) was defined as the time from first dose to the earlier of disease progression or death due to any cause. The duration of PFS was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.
Participants were evaluated for disease response and progression by the investigator according to the IMWG-URC.
Time Frame
From randomization until the data cut-off date of 22 July 2016; median follow-up time for PFS was 13.8 months
Title
Time To Progression
Description
Time to progression (TTP) was defined as the time from first dose to disease progression evaluated by the investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC). TTP was calculated using Kaplan-Meier methods; participants with no baseline and/or post-baseline disease assessments, who started a new anticancer therapy before documentation of disease progression or death, died or had disease progression immediately after more than 1 consecutively missed disease assessment visit or who were alive without documentation of disease progression before the data cutoff date were censored.
Time Frame
From randomization until the data cut-off date of 22 July 2016; median follow-up time for TTP was 13.4 months
Title
Duration of Response
Description
Duration of response (DOR) was defined as the time from first evidence of PR or better to disease progression or death due to any cause. DOR was calculated using Kaplan-Meier methods; Participants with no baseline disease assessments, starting a new anticancer therapy before documentation of disease progression or death, death or disease progression immediately after more than 1 consecutively missed disease assessment visit, or alive without documentation of disease progression before the data cut-off date were censored.
Time Frame
From randomization until the data cut-off date of 22 July 2016; median follow-up time for DOR was 14.3 months
Title
Number of Participants With Adverse Events
Description
Adverse events were graded using National Cancer Institute-Common Terminology Criteria for Adverse Events (version 4.03).
Time Frame
From the first day of study treatment and within 30 days of the last day of study treatment; median duration of treatment was 33.6 weeks.
Title
Time to Maximum Plasma Concentration of Carfilzomib
Time Frame
Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Title
Maximum Plasma Concentration of Carfilzomib
Time Frame
Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Title
Area Under the Plasma Concentration-time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUClast) for Carfilzomib
Time Frame
Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Title
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUCinf) fo Carfilzomib
Time Frame
Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Title
Area Under the Plasma Concentration-time Curve During the Dosing Interval (0-168 Hours) for Carfilzomib
Time Frame
Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Title
Volume of Distribution Observed at Steady State (Vss) for Carfilzomib
Time Frame
Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Title
Terminal Half-life (T1/2,z) for Carfilzomib
Time Frame
Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Title
Clearance of Carfilzomib After IV Infusion
Time Frame
Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
Title
Mean Residence Time Observed From Time Zero to Infinity (MRT0-∞) for Carfilzomib
Time Frame
Day 1 cycle 1 (20 mg/m² carfilzomib), cycle 1 day 15 (phase 1 70 and 88 mg/m² carfilzomib), and cycle 2 day 15 (phase 2 70 mg/m² carfilzomib) from predose to 4 hours after the end of the infusion.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Multiple myeloma with relapsing or progressive disease at study entry
Measurable disease, as defined by 1 or more of the following (assessed within 21 days prior to enrollment):
Serum M-protein ≥ 0.5 g/dL, or
Urine M-protein ≥ 200 mg/24 hours, or
Only in patients who do not meet a or b, then use serum free light chain (SFLC) > 100 mg/L (involved light chain) and an abnormal kappa/lambda ratio
Prior treatment with 1 to 3 prior regimens for multiple myeloma for Phase 1 and Phase 2 (induction therapy followed by stem cell transplant and consolidation/maintenance therapy will be considered as 1 line of therapy
Age ≥ 18 years
Life expectancy ≥ 6 months
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Adequate hepatic function within 21 days prior to enrollment, with bilirubin < 1.5 × the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 × ULN
Left ventricular ejection fraction (LVEF) ≥ 40%. 2-D transthoracic echocardiogram (ECHO) is the preferred method of evaluation. Multigated acquisition scan (MUGA) is acceptable if ECHO is not available
Absolute neutrophil count (ANC) ≥ 1000/mm³ within 21 days prior to enrollment. Screening ANC is to be independent of growth factor support for ≥ 1 week
Hemoglobin ≥ 8.0 g/dL within 21 days prior to enrollment. Use of erythropoietic stimulating factors and red blood cell (RBC) transfusions per institutional guidelines is allowed; however, most recent RBC transfusion must have been at least 7 days prior to obtaining screening hemoglobin
Platelet count ≥ 50,000/mm³ (≥ 30,000/mm³ if myeloma involvement in the bone marrow is > 50%) within 21 days prior to enrollment. Patients must not have received platelet transfusions for at least 7 days prior to obtaining the screening platelet count
Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/min within 21 days prior to enrollment. Calculation based on standard formula, such as the Cockcroft and Gault: [(140 - Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female
Written informed consent in accordance with federal, local, and institutional guidelines
Female patients of childbearing potential (FCBP) must have a negative serum pregnancy test within 21 days prior to enrollment and agree to use an effective method of contraception during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if required per local regulations). Postmenopausal females (> 45 years old and without menses for > 1 year) and surgically sterilized females are exempt from a pregnancy test
Male patients must agree to use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with an FCBP
Exclusion Criteria:
Multiple myeloma of Immunoglobulin M (IgM) subtype
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
Waldenström's macroglobulinemia
Amyloidosis
Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 7 days prior to enrollment
Cytotoxic chemotherapy with approved or investigational anticancer therapeutics within 28 days prior to enrollment
Treatment with bortezomib (Velcade®), thalidomide (Thalomid®) or lenalidomide (Revlimid®) within 21 days prior to enrollment
Focal radiation therapy within 7 days prior to enrollment. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to enrollment (ie, prior radiation must have been to < 30% of the bone marrow)
Immunotherapy within 21 days prior to enrollment
Major surgery within 21 days prior to enrollment
Active congestive heart failure (New York Heart Association [NYHA] Classes III to IV), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within 6 months prior to enrollment
Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B virus [HBV]), or antifungal agents within 14 days prior to enrollment
Known human immunodeficiency virus (HIV) seropositivity
Known hepatitis B or C virus infection (except for patients with HBV who are receiving and responding to HBV antiviral therapy: these patients are allowed)
Patients with known cirrhosis
Second malignancy within the past 3 years, except:
Adequately treated basal cell or squamous cell skin cancer
Carcinoma in situ of the cervix
Prostate cancer < Gleason score 6 with stable prostate-specific antigen (PSA) over 12 months
Breast carcinoma in situ with full surgical resection
Treated medullary or papillary thyroid cancer
Patients with myelodysplastic syndrome
Significant neuropathy (Grades 3 to 4) within 14 days prior to enrollment
Female patients who are pregnant or lactating
Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
Prior carfilzomib treatment
Prior participation in any Onyx-sponsored Phase 3 trial
Patients with contraindication to dexamethasone
Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment
Ongoing graft-versus-host disease
Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrollment
Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment
Any other clinically significant medical disease or psychiatric condition that, in the Investigator's opinion, may interfere with protocol adherence or a patient'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
Arizona Oncology Associates
City
Tucson
State/Province
Arizona
Country
United States
Facility Name
Comprehensive Blood and Cancer Center (CCBC)
City
Bakersfield
State/Province
California
Country
United States
Facility Name
California Cancer Associates for Research and Excellence
City
Encinitas
State/Province
California
Country
United States
Facility Name
Robert A. Moss, M.D., FACP, Inc.
City
Fountain Valley
State/Province
California
Country
United States
Facility Name
California Cancer Associates for Research and Excellence
City
Fresno
State/Province
California
Country
United States
Facility Name
Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Monterey Bay Oncology
City
Salinas
State/Province
California
Country
United States
Facility Name
Sansum Clinic
City
Santa Barbara
State/Province
California
Country
United States
Facility Name
Central Coast Medical Oncology Corporation
City
Santa Maria
State/Province
California
Country
United States
Facility Name
James R. Berenson M.D. Inc.
City
West Hollywood
State/Province
California
Country
United States
Facility Name
The Oncology Insititute of Hope and Innovation
City
Whittier
State/Province
California
Country
United States
Facility Name
Rocky Mountain Cancer Centers
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Florida Cancer Specialists - South
City
Fort Myers
State/Province
Florida
Country
United States
Facility Name
Florida Cancer Specialists - North
City
Tampa
State/Province
Florida
Country
United States
Facility Name
Illinois Cancer Care
City
Galesburg
State/Province
Illinois
Country
United States
Facility Name
Illinois Cancer Specialists
City
Hinsdale
State/Province
Illinois
Country
United States
Facility Name
Illinois Cancer Specialists
City
Niles
State/Province
Illinois
Country
United States
Facility Name
Fort Wayne Oncology & Hematology
City
Fort Wayne
State/Province
Indiana
Country
United States
Facility Name
Horizon Oncology Research, Inc.
City
Lafayette
State/Province
Indiana
Country
United States
Facility Name
Center for Cancer and Blood Disorders (CCBD)
City
Bethesda
State/Province
Maryland
Country
United States
Facility Name
Hematology-Oncology Associates of Northern NJ, PA
City
Morristown
State/Province
New Jersey
Country
United States
Facility Name
New Mexico Cancer Care Alliance
City
Albuquerque
State/Province
New Mexico
Country
United States
Facility Name
Clinical Research Alliance
City
New York
State/Province
New York
Country
United States
Facility Name
Hudson Valley Hematology Oncology Associates
City
Poughkeepsie
State/Province
New York
Country
United States
Facility Name
Willamette Valley Cancer Institute and Research Center
City
Eugene
State/Province
Oregon
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Chattanooga
State/Province
Tennessee
Country
United States
Facility Name
St. Joseph Regional Cancer Center
City
Bryan
State/Province
Texas
Country
United States
Facility Name
Millennium Oncology
City
Houston
State/Province
Texas
Country
United States
Facility Name
Waldron Medical Research and Development Center
City
Houston
State/Province
Texas
Country
United States
Facility Name
Cancer Care Centers of South Texas
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Center at Cancer Therapy & Research Center at The University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
Country
United States
Facility Name
Blood and Cancer Center of East Texas
City
Tyler
State/Province
Texas
Country
United States
Facility Name
Shenandoah Oncology, PC
City
Winchester
State/Province
Virginia
Country
United States
Facility Name
Northwest Cancer Specialists
City
Vancouver
State/Province
Washington
Country
United States
Facility Name
Yakima Valley Memorial Hospital/ North Star Lodge
City
Yakima
State/Province
Washington
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
32108443
Citation
Moreau P, Stewart KA, Dimopoulos M, Siegel D, Facon T, Berenson J, Raje N, Berdeja JG, Orlowski RZ, Yang H, Ma H, Klippel Z, Zahlten-Kumeli A, Mezzi K, Iskander K, Mateos MV. Once-weekly (70 mg/m2 ) vs twice-weekly (56 mg/m2 ) dosing of carfilzomib in patients with relapsed or refractory multiple myeloma: A post hoc analysis of the ENDEAVOR, A.R.R.O.W., and CHAMPION-1 trials. Cancer Med. 2020 May;9(9):2989-2996. doi: 10.1002/cam4.2945. Epub 2020 Feb 28.
Results Reference
background
PubMed Identifier
27207788
Citation
Berenson JR, Cartmell A, Bessudo A, Lyons RM, Harb W, Tzachanis D, Agajanian R, Boccia R, Coleman M, Moss RA, Rifkin RM, Patel P, Dixon S, Ou Y, Anderl J, Aggarwal S, Berdeja JG. CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma. Blood. 2016 Jun 30;127(26):3360-8. doi: 10.1182/blood-2015-11-683854. Epub 2016 May 12.
Results Reference
derived
Learn more about this trial
A Study of Weekly Carfilzomib in Combination With Dexamethasone for Progressive Multiple Myeloma
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