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
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
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California
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Bakersfield、California、アメリカ、93309
- Research Site
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Bakersfield、California、アメリカ
- CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center
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Burbank、California、アメリカ、91505
- Research Site
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Burbank、California、アメリカ
- Providence Saint Joseph Medical Center
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Fountain Valley、California、アメリカ、92708
- Research Site
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Fountain Valley、California、アメリカ
- Compassionate Care Research Group, Inc.
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Los Angeles、California、アメリカ、90017
- Research Site
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Los Angeles、California、アメリカ、90095-1686
- Research Site
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Los Angeles、California、アメリカ
- Los Angeles Hematology / Oncology Medical Group
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Whittier、California、アメリカ、90603
- Research Site
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Colorado
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Aurora、Colorado、アメリカ、80045
- Research Site
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Aurora、Colorado、アメリカ
- University of Colorado
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District of Columbia
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Washington、District of Columbia、アメリカ、20057
- Research Site
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Washington、District of Columbia、アメリカ
- Lombardi Cancer Center, Pediatric Hematology Oncology
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Florida
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Fort Myers、Florida、アメリカ
- Florida Cancer Specialists
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Fort Myers、Florida、アメリカ、33905
- Research Site
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Tampa、Florida、アメリカ、33612
- Research Site
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Tampa、Florida、アメリカ
- H. Lee Moffitt Cancer Center & Research Institute
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West Palm Beach、Florida、アメリカ、33401
- Research Site
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West Palm Beach、Florida、アメリカ
- Florida Cancer Specialists
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Illinois
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Chicago、Illinois、アメリカ
- University Of Chicago Medical Center
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Massachusetts
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Boston、Massachusetts、アメリカ、02114
- Research Site
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Boston、Massachusetts、アメリカ
- Dana Farber Partners Cancer Care
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Michigan
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Ann Arbor、Michigan、アメリカ、48109
- Research Site
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New Jersey
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Hackensack、New Jersey、アメリカ、07601
- Research Site
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Hackensack、New Jersey、アメリカ
- John Theurer Cancer Center at Hackensack University Medical Center
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New York
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New York、New York、アメリカ、10021
- Research Site
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New York、New York、アメリカ、10065
- Research Site
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New York、New York、アメリカ
- Memorial Sloan Kettering
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New York、New York、アメリカ
- Weill Cornell Medical College
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New York、New York、アメリカ
- Clinical Research Alliance
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New York、New York、アメリカ
- Morton Coleman, MD
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Stony Brook、New York、アメリカ、11794
- Research Site
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Stony Brook、New York、アメリカ
- Stony Brook University Medical Center
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North Carolina
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Durham、North Carolina、アメリカ、27705
- Research Site
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Durham、North Carolina、アメリカ
- Durham Veterans Affairs Medical Center
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Ohio
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Cincinnati、Ohio、アメリカ、45242
- Research Site
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Cincinnati、Ohio、アメリカ
- Sarah Cannon Research Institute
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Oregon
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Bend、Oregon、アメリカ、97701
- Research Site
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Bend、Oregon、アメリカ
- Bend Memorial Clinic
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South Carolina
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Charleston、South Carolina、アメリカ、29424
- Research Site
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Charleston、South Carolina、アメリカ
- Medical University of South Carolina, Hollings Cancer Center
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Greenville、South Carolina、アメリカ、29607
- Research Site
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Greenville、South Carolina、アメリカ
- Greenville Health System
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Greenville、South Carolina、アメリカ
- Saint Francis Hospital Cancer Center
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South Dakota
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Sioux Falls、South Dakota、アメリカ、57105
- Research Site
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Sioux Falls、South Dakota、アメリカ
- Avera Cancer Institute
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Tennessee
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Germantown、Tennessee、アメリカ、38138
- Research Site
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Memphis、Tennessee、アメリカ
- The West Clinic, PC
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Nashville、Tennessee、アメリカ、37203
- Research Site
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Nashville、Tennessee、アメリカ、37232
- Research Site
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Nashville、Tennessee、アメリカ
- Vanderbilt University Medical Center
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Nashville、Tennessee、アメリカ
- Tennessee Oncology, PLLC / The Sarah Cannon Research lnstitute
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Utah
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Salt Lake City、Utah、アメリカ、84112
- Research Site
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Salt Lake City、Utah、アメリカ
- Huntsman Cancer Institute
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Washington
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Seattle、Washington、アメリカ、98104
- Research Site
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Seattle、Washington、アメリカ
- Swedish Cancer Institute
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Wisconsin
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Milwaukee、Wisconsin、アメリカ
- Aurora Health Care, Aurora Cancer Care
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Wauwatosa、Wisconsin、アメリカ、53226
- Research Site
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：非ランダム化
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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.
他の名前：
Administered orally once daily on days 1-21 of each 28-day cycle.
他の名前：
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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実験的：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.
他の名前：
Administered orally once daily on days 1-21 of each 28-day cycle.
他の名前：
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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実験的：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.
他の名前：
Administered orally once daily on days 1-21 of each 28-day cycle.
他の名前：
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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実験的：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.
他の名前：
Administered orally once daily on days 1-21 of each 28-day cycle.
他の名前：
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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実験的：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.
他の名前：
Administered orally once daily on days 1-21 of each 28-day cycle.
他の名前：
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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実験的：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.
他の名前：
Administered orally once daily on days 1-21 of each 28-day cycle.
他の名前：
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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of Participants With Adverse Events (AEs)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Maximum Plasma Concentration of Carfilzomib on Day 8 of Cycle 1 by Dose Group
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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.
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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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協力者と研究者
スポンサー
捜査官
- スタディディレクター：Amy Kimball, MD、Amgen
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- CFZ013
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。