Phase 1b Study of Weekly Carfilzomib in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma
Phase 1b Study of Carfilzomib Administered Once Weekly in Combination With Lenalidomide and Dexamethasone in Subjects With Multiple Myeloma
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Studietype
Registrering (Faktiske)
Fase
- Fase 1
Kontakter og plasseringer
Studiesteder
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California
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Bakersfield, California, Forente stater, 93309
- Research Site
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Bakersfield, California, Forente stater
- CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
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Burbank, California, Forente stater, 91505
- Research Site
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Burbank, California, Forente stater
- Providence Saint Joseph Medical Center
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Fountain Valley, California, Forente stater, 92708
- Research Site
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Fountain Valley, California, Forente stater
- Compassionate Care Research Group, Inc.
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Los Angeles, California, Forente stater, 90017
- Research Site
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Los Angeles, California, Forente stater, 90095-1686
- Research Site
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Los Angeles, California, Forente stater
- Los Angeles Hematology / Oncology Medical Group
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Whittier, California, Forente stater, 90603
- Research Site
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Colorado
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Aurora, Colorado, Forente stater, 80045
- Research Site
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Aurora, Colorado, Forente stater
- University of Colorado
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District of Columbia
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Washington, District of Columbia, Forente stater, 20057
- Research Site
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Washington, District of Columbia, Forente stater
- Lombardi Cancer Center, Pediatric Hematology Oncology
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Florida
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Fort Myers, Florida, Forente stater
- Florida Cancer Specialists
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Fort Myers, Florida, Forente stater, 33905
- Research Site
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Tampa, Florida, Forente stater, 33612
- Research Site
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Tampa, Florida, Forente stater
- H. Lee Moffitt Cancer Center & Research Institute
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West Palm Beach, Florida, Forente stater, 33401
- Research Site
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West Palm Beach, Florida, Forente stater
- Florida Cancer Specialists
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Illinois
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Chicago, Illinois, Forente stater
- University Of Chicago Medical Center
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Massachusetts
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Boston, Massachusetts, Forente stater, 02114
- Research Site
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Boston, Massachusetts, Forente stater
- Dana Farber Partners Cancer Care
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Michigan
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Ann Arbor, Michigan, Forente stater, 48109
- Research Site
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New Jersey
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Hackensack, New Jersey, Forente stater, 07601
- Research Site
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Hackensack, New Jersey, Forente stater
- John Theurer Cancer Center at Hackensack University Medical Center
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New York
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New York, New York, Forente stater, 10021
- Research Site
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New York, New York, Forente stater, 10065
- Research Site
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New York, New York, Forente stater
- Memorial Sloan Kettering
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New York, New York, Forente stater
- Weill Cornell Medical College
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New York, New York, Forente stater
- Clinical Research Alliance
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New York, New York, Forente stater
- Morton Coleman, MD
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Stony Brook, New York, Forente stater, 11794
- Research Site
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Stony Brook, New York, Forente stater
- Stony Brook University Medical Center
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North Carolina
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Durham, North Carolina, Forente stater, 27705
- Research Site
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Durham, North Carolina, Forente stater
- Durham Veterans Affairs Medical Center
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Ohio
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Cincinnati, Ohio, Forente stater, 45242
- Research Site
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Cincinnati, Ohio, Forente stater
- Sarah Cannon Research Institute
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Oregon
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Bend, Oregon, Forente stater, 97701
- Research Site
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Bend, Oregon, Forente stater
- Bend Memorial Clinic
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South Carolina
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Charleston, South Carolina, Forente stater, 29424
- Research Site
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Charleston, South Carolina, Forente stater
- Medical University of South Carolina, Hollings Cancer Center
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Greenville, South Carolina, Forente stater, 29607
- Research Site
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Greenville, South Carolina, Forente stater
- Greenville Health System
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Greenville, South Carolina, Forente stater
- Saint Francis Hospital Cancer Center
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South Dakota
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Sioux Falls, South Dakota, Forente stater, 57105
- Research Site
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Sioux Falls, South Dakota, Forente stater
- Avera Cancer Institute
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Tennessee
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Germantown, Tennessee, Forente stater, 38138
- Research Site
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Memphis, Tennessee, Forente stater
- The West Clinic, PC
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Nashville, Tennessee, Forente stater, 37203
- Research Site
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Nashville, Tennessee, Forente stater, 37232
- Research Site
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Nashville, Tennessee, Forente stater
- Vanderbilt University Medical Center
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Nashville, Tennessee, Forente stater
- Tennessee Oncology, PLLC / The Sarah Cannon Research lnstitute
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Utah
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Salt Lake City, Utah, Forente stater, 84112
- Research Site
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Salt Lake City, Utah, Forente stater
- Huntsman Cancer Institute
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Washington
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Seattle, Washington, Forente stater, 98104
- Research Site
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Seattle, Washington, Forente stater
- Swedish Cancer Institute
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Wisconsin
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Milwaukee, Wisconsin, Forente stater
- Aurora Health Care, Aurora Cancer Care
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Wauwatosa, Wisconsin, Forente stater, 53226
- Research Site
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
Key Inclusion Criteria:
- Newly diagnosed or relapsed multiple myeloma
- Measureable disease by serum M protein, or urine M protein, or serum free light chain (SFLC) and an abnormal serum kappa lambda ratio (for subjects without detectable serum or urine M-protein), or serum quantitative immunoglobulin A (glgA) (for immunoglobulin (Ig) A subjects whose disease can only be reliable measured by qlgA).
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2
- Left ventricular ejection fraction (LVEF) ≥ 40%
Key Exclusion Criteria:
- Waldenström macroglobulinemia
- For newly diagnosed multiple myeloma: multiple myeloma of IgM subtype
For relapsed disease:
- If treated with a lenalidomide and dexamethasone combination, progression during the first 3 months after initiating treatment.
- Any progression during treatment if the lenalidomide and dexamethasone regimen was the most recent line of therapy.
- Any prior treatment with carfilzomib
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Plasma cell leukemia (> 2.0 × 10^9/L circulating plasma cells by standard differential)
- Myelodysplastic syndrome
- Amyloidosis
- Prior treatment with carfilzomib or oprozomib
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomisert
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
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Eksperimentell: RRMM Dose-evaluation: Carfilzomib 56 mg/m²
Participants with relapsed or refractory multiple myeloma (RRMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. |
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
Andre navn:
Administered orally once daily on days 1-21 of each 28-day cycle.
Andre navn:
Administered by mouth or IV at 40 mg on days 1, 8, and 15 of each 28-day cycle and on day 22 of cycles 1 to 8.
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Eksperimentell: RRMM Dose-evaluation: Carfilzomib 70 mg/m²
Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. |
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
Andre navn:
Administered orally once daily on days 1-21 of each 28-day cycle.
Andre navn:
Administered by mouth or IV at 40 mg on days 1, 8, and 15 of each 28-day cycle and on day 22 of cycles 1 to 8.
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Eksperimentell: RRMM Dose-expansion: Carfilzomib 70 mg/m²
Participants with RRMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. |
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
Andre navn:
Administered orally once daily on days 1-21 of each 28-day cycle.
Andre navn:
Administered by mouth or IV at 40 mg on days 1, 8, and 15 of each 28-day cycle and on day 22 of cycles 1 to 8.
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Eksperimentell: NDMM Dose-evaluation: Carfilzomib 56/70 mg/m²
Participants with newly diagnosed multiple myeloma (NDMM) received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1 day 1, 56 mg/m² on cycle 1 days 8 and 15, and then 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. |
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
Andre navn:
Administered orally once daily on days 1-21 of each 28-day cycle.
Andre navn:
Administered by mouth or IV at 40 mg on days 1, 8, and 15 of each 28-day cycle and on day 22 of cycles 1 to 8.
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Eksperimentell: NDMM Dose-expansion: Carfilzomib 70 mg/m²
Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 70 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. |
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
Andre navn:
Administered orally once daily on days 1-21 of each 28-day cycle.
Andre navn:
Administered by mouth or IV at 40 mg on days 1, 8, and 15 of each 28-day cycle and on day 22 of cycles 1 to 8.
|
|
Eksperimentell: NDMM Dose-expansion: Carfilzomib 56 mg/m²
Participants with NDMM received treatment with carfilzomib, lenalidomide, and dexamethasone (KRd) for up to eighteen 28-day cycles, or until disease progression, patient withdrawal, stem cell transplant, or death. Participants received carfilzomib on days 1, 8, and 15 of each cycle. The dose was 20 mg/m² on cycle 1, day 1, and 56 mg/m² thereafter. Participants also received lenalidomide 25 mg once daily on days 1-21 and dexamethasone 40 mg (oral or IV) on days 1, 8, and 15 of each cycle, and on day 22 of cycles 1 to 8. |
Administered once weekly by 30-minute intravenous (IV) infusion on days 1, 8, and 15 of each 28-day cycle.
Andre navn:
Administered orally once daily on days 1-21 of each 28-day cycle.
Andre navn:
Administered by mouth or IV at 40 mg on days 1, 8, and 15 of each 28-day cycle and on day 22 of cycles 1 to 8.
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Number of Participants With Adverse Events (AEs)
Tidsramme: From the first dose of any study drug up to 30 days after the last dose of any study drug; median (range) duration of treatment with carfilzomib was 32 (1.1, 76.7) weeks in RRMM participants and 26 (1.0, 94.4) weeks in NDMM participants.
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Safety and tolerability were evaluated according to the type, incidence, and severity of adverse events. An AE is defined as any untoward medical occurrence in a clinical trial subject. The event does not necessarily have a causal relationship with study treatment. A serious adverse event is defined as an AE that meets at least 1 of the following serious criteria:
The severity of each AE was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death. |
From the first dose of any study drug up to 30 days after the last dose of any study drug; median (range) duration of treatment with carfilzomib was 32 (1.1, 76.7) weeks in RRMM participants and 26 (1.0, 94.4) weeks in NDMM participants.
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Change From Baseline in Hemoglobin Levels
Tidsramme: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
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Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
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Change From Baseline in Platelet Count
Tidsramme: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
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Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
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Change From Baseline in Neutrophil Count
Tidsramme: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
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Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
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Change From Baseline in Bilirubin
Tidsramme: Baseline and Cycle 2 day 1
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Baseline and Cycle 2 day 1
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Change From Baseline in Creatinine
Tidsramme: Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
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Baseline and Cycle 1, days 8 and 15 and Cycle 2 days 1, 8, and 15
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Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Tidsramme: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
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Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
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Time to Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Tidsramme: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
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Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
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Area Under the Curve From Time Zero to Time of Last Quantifiable Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Tidsramme: Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
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Day 8 of Cycle 1 at predose, 15 minutes after the start of infusion, at the end of infusion, and 15 and 60 minutes after the end of infusion
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Overall Response Rate (ORR)
Tidsramme: Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
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Response was determined by the investigator based on the International Myeloma Working Group Uniform Response Criteria (IMWG URC). ORR was defined as the percentage of participants who achieved a best response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Responses must have been confirmed in 2 consecutive assessments at any time prior to initiation of any new therapy. Disease assessments included serum protein electrophoresis (SPEP) with immunofixation, urine protein electrophoresis (UPEP; 24-hour assessment) with immunofixation, serum free light chain (SFLC), quantitative immunoglobulins, bone marrow aspirates to determine percent plasma cell involvement, and skeletal imaging for plasmacytoma evaluation. |
Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
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Complete Response Rate (CRR)
Tidsramme: Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
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Complete Response Rate (CRR) is defined as the percentage of participants who achieved a best overall response of either stringent complete response (sCR) or complete response (CR) in accordance with International Myeloma Working Group-Uniform Response Criteria (IMWG-URC). sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM) CR: Negative serum and urine immunofixation, disappearance of any soft tissue plasmacytomas, < 5% plasma cells in BM, and normal SFLC ratio in participants with measurable disease only by SFLC. |
Response assessments were performed on day 1 of each treatment cycle from cycle 2 and then every 8 weeks during follow-up until disease progression. Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
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Progression-free Survival (PFS)
Tidsramme: From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
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PFS is defined as the time from the first day of study treatment to the earlier of disease progression or death due to any cause. Disease progression was determined by the investigator according to IMWG-URC. Progressive Disease (PD): Increase of 25% from lowest value in serum M-component (absolute increase ≥ 0.5 g/dL), urine M-component (absolute increase ≥ 200 mg per 24 hours) and/or the difference between involved and uninvolved FLC levels (absolute increase >10 mg/dL) in patients without measurable serum and urine M-protein levels, and/or any new or increase in size of bone lesions or soft tissue plasmacytomas, or development of hypercalcemia. PFS was analyzed using Kaplan-Meier methods. Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after > 1 consecutively missed assessment visit, were lost to follow-up or withdrew consent were censored at the date of last disease assessment. |
From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
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Duration of Response (DOR)
Tidsramme: From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
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Duration of response (DOR) was calculated for participants who achieved a confirmed PR or better based on Investigator assessment and according to the IMWG URC.
Duration of overall response is defined as the time from first documentation of response to disease progression or death due to any cause.
DOR was analyzed using Kaplan-Meier methods.
Participants who were alive with no documented PD, started new anticancer therapy before documentation of PD or death, had death or PD immediately after > 1 consecutively missed disease assessment visit, were lost to follow-up, or withdrew consent were censored at the date of last disease assessment.
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From first dose of study drug until the end of follow-up; Median time on follow-up was 10.6 months in RRMM participants and 6.9 months in NDMM participants.
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Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studieleder: Amy Kimball, MD, Amgen
Publikasjoner og nyttige lenker
Hjelpsomme linker
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Kardiovaskulære sykdommer
- Vaskulære sykdommer
- Sykdommer i immunsystemet
- Neoplasmer etter histologisk type
- Neoplasmer
- Lymfoproliferative lidelser
- Immunproliferative lidelser
- Hematologiske sykdommer
- Hemoragiske lidelser
- Hemostatiske lidelser
- Paraproteinemier
- Blodproteinforstyrrelser
- Multippelt myelom
- Neoplasmer, plasmacelle
- Fysiologiske effekter av legemidler
- Autonome agenter
- Agenter fra det perifere nervesystemet
- Anti-inflammatoriske midler
- Antineoplastiske midler
- Immunologiske faktorer
- Antiemetika
- Gastrointestinale midler
- Glukokortikoider
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Antineoplastiske midler, hormonelle
- Angiogenese-hemmere
- Angiogenesemodulerende midler
- Vekststoffer
- Veksthemmere
- Deksametason
- Lenalidomid
Andre studie-ID-numre
- CFZ013
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
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