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
Обзор исследования
Статус
Условия
Вмешательство/лечение
Тип исследования
Регистрация (Действительный)
Фаза
- Фаза 1
Контакты и местонахождение
Места учебы
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California
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Bakersfield, California, Соединенные Штаты, 93309
- Research Site
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Bakersfield, California, Соединенные Штаты
- CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
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Burbank, California, Соединенные Штаты, 91505
- Research Site
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Burbank, California, Соединенные Штаты
- Providence Saint Joseph Medical Center
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Fountain Valley, California, Соединенные Штаты, 92708
- Research Site
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Fountain Valley, California, Соединенные Штаты
- Compassionate Care Research Group, Inc.
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Los Angeles, California, Соединенные Штаты, 90017
- Research Site
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Los Angeles, California, Соединенные Штаты, 90095-1686
- Research Site
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Los Angeles, California, Соединенные Штаты
- Los Angeles Hematology / Oncology Medical Group
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Whittier, California, Соединенные Штаты, 90603
- Research Site
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Colorado
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Aurora, Colorado, Соединенные Штаты, 80045
- Research Site
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Aurora, Colorado, Соединенные Штаты
- University of Colorado
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District of Columbia
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Washington, District of Columbia, Соединенные Штаты, 20057
- Research Site
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Washington, District of Columbia, Соединенные Штаты
- Lombardi Cancer Center, Pediatric Hematology Oncology
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Florida
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Fort Myers, Florida, Соединенные Штаты
- Florida Cancer Specialists
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Fort Myers, Florida, Соединенные Штаты, 33905
- Research Site
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Tampa, Florida, Соединенные Штаты, 33612
- Research Site
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Tampa, Florida, Соединенные Штаты
- H. Lee Moffitt Cancer Center & Research Institute
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West Palm Beach, Florida, Соединенные Штаты, 33401
- Research Site
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West Palm Beach, Florida, Соединенные Штаты
- Florida Cancer Specialists
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Illinois
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Chicago, Illinois, Соединенные Штаты
- University Of Chicago Medical Center
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Massachusetts
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Boston, Massachusetts, Соединенные Штаты, 02114
- Research Site
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Boston, Massachusetts, Соединенные Штаты
- Dana Farber Partners Cancer Care
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Michigan
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Ann Arbor, Michigan, Соединенные Штаты, 48109
- Research Site
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New Jersey
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Hackensack, New Jersey, Соединенные Штаты, 07601
- Research Site
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Hackensack, New Jersey, Соединенные Штаты
- John Theurer Cancer Center at Hackensack University Medical Center
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New York
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New York, New York, Соединенные Штаты, 10021
- Research Site
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New York, New York, Соединенные Штаты, 10065
- Research Site
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New York, New York, Соединенные Штаты
- Memorial Sloan Kettering
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New York, New York, Соединенные Штаты
- Weill Cornell Medical College
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New York, New York, Соединенные Штаты
- Clinical Research Alliance
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New York, New York, Соединенные Штаты
- Morton Coleman, MD
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Stony Brook, New York, Соединенные Штаты, 11794
- Research Site
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Stony Brook, New York, Соединенные Штаты
- Stony Brook University Medical Center
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North Carolina
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Durham, North Carolina, Соединенные Штаты, 27705
- Research Site
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Durham, North Carolina, Соединенные Штаты
- Durham Veterans Affairs Medical Center
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Ohio
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Cincinnati, Ohio, Соединенные Штаты, 45242
- Research Site
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Cincinnati, Ohio, Соединенные Штаты
- Sarah Cannon Research Institute
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Oregon
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Bend, Oregon, Соединенные Штаты, 97701
- Research Site
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Bend, Oregon, Соединенные Штаты
- Bend Memorial Clinic
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South Carolina
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Charleston, South Carolina, Соединенные Штаты, 29424
- Research Site
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Charleston, South Carolina, Соединенные Штаты
- Medical University of South Carolina, Hollings Cancer Center
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Greenville, South Carolina, Соединенные Штаты, 29607
- Research Site
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Greenville, South Carolina, Соединенные Штаты
- Greenville Health System
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Greenville, South Carolina, Соединенные Штаты
- Saint Francis Hospital Cancer Center
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South Dakota
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Sioux Falls, South Dakota, Соединенные Штаты, 57105
- Research Site
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Sioux Falls, South Dakota, Соединенные Штаты
- Avera Cancer Institute
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Tennessee
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Germantown, Tennessee, Соединенные Штаты, 38138
- Research Site
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Memphis, Tennessee, Соединенные Штаты
- The West Clinic, PC
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Nashville, Tennessee, Соединенные Штаты, 37203
- Research Site
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Nashville, Tennessee, Соединенные Штаты, 37232
- Research Site
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Nashville, Tennessee, Соединенные Штаты
- Vanderbilt University Medical Center
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Nashville, Tennessee, Соединенные Штаты
- Tennessee Oncology, PLLC / The Sarah Cannon Research lnstitute
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Utah
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Salt Lake City, Utah, Соединенные Штаты, 84112
- Research Site
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Salt Lake City, Utah, Соединенные Штаты
- Huntsman Cancer Institute
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Washington
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Seattle, Washington, Соединенные Штаты, 98104
- Research Site
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Seattle, Washington, Соединенные Штаты
- Swedish Cancer Institute
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Wisconsin
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Milwaukee, Wisconsin, Соединенные Штаты
- Aurora Health Care, Aurora Cancer Care
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Wauwatosa, Wisconsin, Соединенные Штаты, 53226
- Research Site
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Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
Принимает здоровых добровольцев
Полы, имеющие право на обучение
Описание
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
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Нерандомизированный
- Интервенционная модель: Одногрупповое задание
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
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Экспериментальный: 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.
Другие имена:
Administered orally once daily on days 1-21 of each 28-day cycle.
Другие имена:
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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Экспериментальный: 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.
Другие имена:
Administered orally once daily on days 1-21 of each 28-day cycle.
Другие имена:
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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Экспериментальный: 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.
Другие имена:
Administered orally once daily on days 1-21 of each 28-day cycle.
Другие имена:
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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Экспериментальный: 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.
Другие имена:
Administered orally once daily on days 1-21 of each 28-day cycle.
Другие имена:
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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|
Экспериментальный: 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.
Другие имена:
Administered orally once daily on days 1-21 of each 28-day cycle.
Другие имена:
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.
|
|
Экспериментальный: 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.
Другие имена:
Administered orally once daily on days 1-21 of each 28-day cycle.
Другие имена:
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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Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Number of Participants With Adverse Events (AEs)
Временное ограничение: 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.
|
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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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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Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
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Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
Временное ограничение: 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
|
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
Временное ограничение: 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
Временное ограничение: 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
|
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)
Временное ограничение: 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.
|
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.
|
|
Complete Response Rate (CRR)
Временное ограничение: 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.
|
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)
Временное ограничение: 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.
|
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.
|
|
Duration of Response (DOR)
Временное ограничение: 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.
|
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.
|
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.
|
Соавторы и исследователи
Спонсор
Следователи
- Директор по исследованиям: Amy Kimball, MD, Amgen
Публикации и полезные ссылки
Полезные ссылки
Даты записи исследования
Изучение основных дат
Начало исследования (Действительный)
Первичное завершение (Действительный)
Завершение исследования (Действительный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Оценивать)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Дополнительные соответствующие термины MeSH
- Сердечно-сосудистые заболевания
- Сосудистые заболевания
- Заболевания иммунной системы
- Новообразования по гистологическому типу
- Новообразования
- Лимфопролиферативные заболевания
- Иммунопролиферативные заболевания
- Гематологические заболевания
- Геморрагические расстройства
- Нарушения гемостаза
- Парапротеинемии
- Нарушения белков крови
- Множественная миелома
- Новообразования, Плазматические клетки
- Физиологические эффекты лекарств
- Автономные агенты
- Агенты периферической нервной системы
- Противовоспалительные агенты
- Противоопухолевые агенты
- Иммунологические факторы
- Противорвотные средства
- Желудочно-кишечные агенты
- Глюкокортикоиды
- Гормоны
- Гормоны, заменители гормонов и антагонисты гормонов
- Противоопухолевые агенты, гормональные
- Ингибиторы ангиогенеза
- Агенты, модулирующие ангиогенез
- Вещества роста
- Ингибиторы роста
- Дексаметазон
- Леналидомид
Другие идентификационные номера исследования
- CFZ013
Планирование данных отдельных участников (IPD)
Планируете делиться данными об отдельных участниках (IPD)?
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