Phase 1b/2, Multicenter, Open-label Study of Oprozomib, Melphalan, and Prednisone in Transplant Ineligible Patients With Newly Diagnosed Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 9
- 试验地点
- 8
- 主要终点
- Overall Response Rate (ORR) - Phase 2
研究概览
简要总结
The purpose of Phase 1b of the study is to determine the maximum tolerated dose (MTD) of oprozomib in combination with melphalan and prednisone (OMP).
The purpose of Phase 2 of the study is to estimate the overall response rate (ORR) and complete response rate (CRR) of the OMP combination.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed symptomatic multiple myeloma patients who are transplant ineligible with measureable disease as indicated by one or more of the following:
- •Serum M-protein ≥ 500 mg/dL
- •Urine M-protein ≥ 200 mg/24 hour
- •Serum Free Light Chain: Involved free light chain (FLC) level ≥ 10 mg/dL, provided serum FLC ratio is abnormal
- •Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- •Creatinine clearance (CrCl) ≥ 30 mL/min, either measured or calculated using the formula of Cockcroft and Gault [(140 - age) × mass (kg) / (72 × serum creatinine mg/dL)]. Multiply result by 0.85 if female.
排除标准
- •Any prior systemic antimyeloma therapy except oral steroids (dexamethasone up to a total dose of 160 mg or equivalent within 14 days prior to the first dose of study treatment is allowed). Use of topical or inhaled steroids is acceptable.
- •Congestive heart failure (New York Hearth Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months prior to first dose
- •Known or suspected HIV, active Hepatitis A, B C or virus infection (Exception: Subjects with chronic or cleared HBV and HCV infection and stable liver function tests [bilirubin, AST] will be allowed).
- •Significant neuropathy (Grade 2 with pain or higher) at the time of first dose.
- •Plasma cell leukemia.
- •POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- •Known amyloidosis
研究组 & 干预措施
Oprozomib with Melphalan and Prednisone (OMP)
Subjects will receive oprozomib administered orally.
The combination of oprozomib, melphalan, and prednisone (OMP) will be administered until progression of disease, unacceptable toxicity, discontinuation of study treatment for reasons other than progression or toxicity, or a maximum of 9 cycles (54 weeks), whichever occurs first.
干预措施: Oprozomib (Drug)
Oprozomib with Melphalan and Prednisone (OMP)
Subjects will receive oprozomib administered orally.
The combination of oprozomib, melphalan, and prednisone (OMP) will be administered until progression of disease, unacceptable toxicity, discontinuation of study treatment for reasons other than progression or toxicity, or a maximum of 9 cycles (54 weeks), whichever occurs first.
干预措施: Melphalan (Drug)
Oprozomib with Melphalan and Prednisone (OMP)
Subjects will receive oprozomib administered orally.
The combination of oprozomib, melphalan, and prednisone (OMP) will be administered until progression of disease, unacceptable toxicity, discontinuation of study treatment for reasons other than progression or toxicity, or a maximum of 9 cycles (54 weeks), whichever occurs first.
干预措施: Prednisone (Drug)
结局指标
主要结局
Overall Response Rate (ORR) - Phase 2
时间窗: 39 months
ORR defined as a best overall response of sCR, CR, VGPR, or PR according to the IMWG-URC.
Maximum Tolerated Dose (MTD) - Phase 1b
时间窗: 42 weeks
MTD is defined as the highest dose at which a DLT is observed in less than 2 of 6 evaluable subjects occurring within the 4 weeks after the first dose of combination therapy.
Complete Response Rate (CRR) - Phase 2
时间窗: 39 months
CRR defined as a best overall response of sCR or CR according to the IMWG-URC.
次要结局
- Population Pharmacokinetic (PK) parameters - apparent clearance and volume of distribution(2 postdose time points in Cycle 1 Day 1, 1 predose and 2 postdose time points on Cycle 3 Day 1 and Cycle 5 Day 1)
- Adverse Events (AEs) and Serious Adverse Events (SAEs) - Phase 2(Collected from signing of informed consent and throughout study until 30 days after the last dose of study treatment (up to 58 weeks))
- Duration of Response (DOR)(39 months)
- Progression-free Survival (PFS)(39 months)