A Phase 1 Study of Tabalumab (LY2127399) in Combination With Bortezomib and Dexamethasone in Japanese Patients With Relapsed or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs
研究概览
简要总结
The purpose of this study is to evaluate the safety and effect on the body of Tabalumab (LY2127399) in combination with bortezomib and dexamethasone in Japanese participants with relapsed or refractory multiple myeloma (MM).
详细描述
The study has 3 cohorts. Cohort 2 and cohort 2-SC will be conducted in parallel with some data presented combined.
Cohort 1 - Participants will receive 100 mg Tabalumab (LY2127399) intravenously (IV), 1.3 milligram per square meter (mg/m^2) bortezomib IV, and 20 mg dexamethasone orally.
Cohort 2 - Participants will receive 300 mg Tabalumab (LY2127399) IV, 1.3 mg/m^2 bortezomib IV, and 20 mg dexamethasone orally.
Cohort 2-SC - Participants will receive 300 mg Tabalumab (LY2127399) IV, 1.3 mg/m^2 bortezomib subcutaneously (SC), and 20 mg dexamethasone orally.
Cohort 2-SC was added per protocol amendment in February 2013.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have relapsed or refractory MM treated with at least 1 prior regimen. Prior therapy with bortezomib is allowed if there was previously at least a minimal response (MR).
- •Have measurable disease as defined by one or more of the following:
- •serum M-protein concentration ≥ 1 g/dL (10 g/L)
- •urine monoclonal light chain concentration ≥ 200 mg/24 hours as determined by urine protein electrophoresis
- •involved serum free light chain (SFLC) concentration ≥ 10 mg/dL (100 mg/L) and an abnormal SFLC ratio
- •Have adequate organ function including:
- •Absolute neutrophil count (ANC) ≥ 1000/microliter
- •Platelet (PLT) count ≥ 75,000/microliter
- •Hemoglobin (Hgb) ≥ 8.0 g/dL
- •Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (if total is elevated check direct and, if normal, participant is eligible)
- •Aspartate transaminase (AST) and alanine aminotransferase (ALT) are ≤ 3 x ULN
- •Serum creatinine ≤ 3.0 mg/dL.
- •Have an Eastern Cooperative Oncology Group performance status (ECOG PS) score of ≤
- •Have discontinued all previous therapies for cancer, including chemotherapy, surgery, and radiotherapy for at least 2 weeks (6 weeks for mitomycin-C or nitrosoureas) before study enrollment and recovered from the acute effects of therapy.
- •Males and females with reproductive potential: Must agree to use medically approved contraceptive precautions during the study and for 4 months following the last dose of study drug.
- •Females with childbearing potential: Must have had a negative urine or serum pregnancy test <7 days before the first dose of study drug.
- •Have an estimated life expectancy of ≥16 weeks, in the opinion of the investigator.
排除标准
- •Have received treatment within 30 days of the initial dose of study drug with an experimental agent for non-cancer indications that has not received regulatory approval for any indication.
- •Have one or more serious preexisting medical conditions that, in the opinion of the investigator, would preclude participation in this study.
- •Have an uncontrolled infection.
- •Females who are pregnant or breastfeeding.
- •Have known positive test results for human immunodeficiency virus (HIV), hepatitis B*, or hepatitis C antibodies (HCAb).
- •* Have evidence of or test positive for hepatitis B. A positive test for hepatitis B is defined as:
- •positive for hepatitis B surface antigen (HBsAg+). OR
- •positive for anti-hepatitis B core antibody and positive for hepatitis B deoxyribonucleic acid (HBV DNA).
- •positive for anti-hepatitis B surface antibody (HBsAb+) and positive for hepatitis B deoxyribonucleic acid (HBV DNA).
- •Have ≥ Grade 2 peripheral neuropathy or any grade with pain as assessed using the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE v 4.03).
- •Have previously received an allogenic hematopoietic stem cell transplant.
- •Have previously received treatment with an experimental agent that targets B-cell activating factor (BAFF).
- •Have a corrected QT (QTc) interval >470 msec on their baseline electrocardiogram (ECG).
- •Have interstitial pneumonitis (interstitial pneumonia) or pulmonary fibrosis manifested as opacity on chest X-ray or computed tomography (CT) scan.
- •Have had another active malignancy within the past 5 years.
研究组 & 干预措施
300 mg Tabalumab+BTZ IV+Dex
Cohort 2. 300 mg tabalumab (LY2127399) IV on day 1 of each cycle, each cycle is 21 days. BTZ, 1.3 mg/m^2, IV on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dex, 20 mg/day, on day of and day after BTZ.
干预措施: Tabalumab (Biological)
100 mg Tabalumab+Bortezomib (BTZ)IV+Dexamethasone (Dex)
Cohort 1. 100 mg tabalumab (LY2127399) intravenously (IV) on day 1 of each cycle, each cyle is 21 days. Bortezomib (BTZ), 1.3 milligram per square meter (mg/m^2), IV on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dexamethasone (Dex), 20 mg/day, on day of and day after BTZ.
干预措施: Tabalumab (Biological)
100 mg Tabalumab+Bortezomib (BTZ)IV+Dexamethasone (Dex)
Cohort 1. 100 mg tabalumab (LY2127399) intravenously (IV) on day 1 of each cycle, each cyle is 21 days. Bortezomib (BTZ), 1.3 milligram per square meter (mg/m^2), IV on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dexamethasone (Dex), 20 mg/day, on day of and day after BTZ.
干预措施: Bortezomib IV (Drug)
100 mg Tabalumab+Bortezomib (BTZ)IV+Dexamethasone (Dex)
Cohort 1. 100 mg tabalumab (LY2127399) intravenously (IV) on day 1 of each cycle, each cyle is 21 days. Bortezomib (BTZ), 1.3 milligram per square meter (mg/m^2), IV on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dexamethasone (Dex), 20 mg/day, on day of and day after BTZ.
干预措施: Dexamethasone (Drug)
300 mg Tabalumab+BTZ IV+Dex
Cohort 2. 300 mg tabalumab (LY2127399) IV on day 1 of each cycle, each cycle is 21 days. BTZ, 1.3 mg/m^2, IV on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dex, 20 mg/day, on day of and day after BTZ.
干预措施: Bortezomib IV (Drug)
300 mg Tabalumab+BTZ IV+Dex
Cohort 2. 300 mg tabalumab (LY2127399) IV on day 1 of each cycle, each cycle is 21 days. BTZ, 1.3 mg/m^2, IV on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dex, 20 mg/day, on day of and day after BTZ.
干预措施: Dexamethasone (Drug)
300 mg Tabalumab+BTZ SC+Dex
Cohort 2-SC. 300 mg tabalumab (LY2127399)IV on day 1 of each cycle, each cycle is 21 days. BTZ, 1.3 mg/m^2, subcutaneously (SC) on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dex, 20 mg/day, on day of and day after BTZ. Cohort 2-SC was added per protocol amendment in February 2013.
干预措施: Tabalumab (Biological)
300 mg Tabalumab+BTZ SC+Dex
Cohort 2-SC. 300 mg tabalumab (LY2127399)IV on day 1 of each cycle, each cycle is 21 days. BTZ, 1.3 mg/m^2, subcutaneously (SC) on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dex, 20 mg/day, on day of and day after BTZ. Cohort 2-SC was added per protocol amendment in February 2013.
干预措施: Bortezomib SC (Drug)
300 mg Tabalumab+BTZ SC+Dex
Cohort 2-SC. 300 mg tabalumab (LY2127399)IV on day 1 of each cycle, each cycle is 21 days. BTZ, 1.3 mg/m^2, subcutaneously (SC) on days 1, 4, 8, 11 of Cycle 1-8, then on days 1, 8, 15, 22 from Cycle 9 onward. Oral dex, 20 mg/day, on day of and day after BTZ. Cohort 2-SC was added per protocol amendment in February 2013.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Number of Participants With One or More Drug Related Adverse Events (AEs) or Any Serious AEs
时间窗: Baseline through 8 months
A summary of other non-serious AEs, and all SAE's, regardless of causality, is located in the Reported Adverse Events section.
次要结局
- Pharmacokinetics (PK): Maximum Plasma Concentration (Cmax) for Tabalumab (LY2127399)(Cycle 1, Day 1: 6 + or - hours after bortezomib (BTZ); Cycle 7, Day 1: immediately post BTZ dose and 2 hours after tabalumab)
- Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-∞) of Tabalumab (LY2127399)(Cycle 1, Day 1: 6 + or - hours after bortezomib (BTZ); Cycle 7, Day 1: immediately post BTZ dose and 2 hours after tabalumab)
- Time to Progression (TTP)(Baseline to date of Progressive Disease (up to 455 days))
- Pharmacodynamics (PD): Change From Baseline in B-cell Subset Fractions(Baseline, Cycle 1 and Cycle 7: prior to first tabalumab dose.)
- Pharmacokinetics (PK): Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Plasma Concentration (AUC0-tlast) of Tabalumab (LY2127399)(Cycle 1, Day 1: 6 + or - hours after bortezomib (BTZ); Cycle 7, Day 1: immediately post BTZ dose and 2 hours after tabalumab)
- Number of Participants With Tumor Response (Tumor Response Rate)(Baseline to disease progression (up to 421 days))
- Duration of Response (DoR)(Time from Response until measured Progressive Disease (up to 455 days))
- Pharmacodynamics (PD): Change From Baseline in Absolute B-cell Count(Baseline through study completion (up to 455 days))