An Open-Label, Single-Arm Study of ATG-010 Plus Dexamethasone in Patients With Multiple Myeloma Refractory to Prior Treatment With Immunomodulatory Agents and Proteasome Inhibitor
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 82
- 试验地点
- 17
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This is an open-label, single-arm study of ATG-010 (selinexor) plus low-dose Dexamethasone (Sd) in patients with multiple myeloma previously treated with lenalidomide and bortezomib refractory to prior treatment with immunomodulatory agents and proteasome Inhibitors.
详细描述
This is a single-arm, open-label, multicenter study of ATG-010 (Selinexor) plus low dose Dexamethasone dosed twice weekly each week in four-week cycles, in patients with triple-refractory MM. The population refractory for the primary efficacy analysis will contain only patients with triple-MM enrolled. PK analysis would be performed which would contain approximately 30% of the patients enrolled. Safety analyses will be performed on the overall population of patients who received at least one dose of study drug among triple-refractory patient populations. Patients will receive treatment until progressive disease (PD), death, toxicity that cannot be managed by standard care, or withdrawal, whichever occurs first.
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
- •Written informed consent in accordance with federal, local, and institutional guidelines.
- •Age ≥ 18 years at the time of signing informed consent.
- •Patients must have previously received including proteasome inhibitors (PI) (i.e., lenalidomide) and immunomodulatory drugs (i.e., bortezomib) and were refractory to both drugs.
- •Any clinically significant non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #17) that patients experienced from treatments in previous clinical studies must have resolved to Grade ≤ 2 by Cycle 1 Day
- •Adequate hepatic function within 21 days prior to Cycle 1 Day 1: total bilirubin < 2x upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3x ULN), AST < 2.5x ULN and ALT < 2.5x ULN.
- •Adequate renal function within 21 days prior to Cycle 1 Day 1: estimated creatinine clearance of ≥ 20 mL/min, calculated using the formula of cockroft and gault.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤
- •Measurable MM based on IMWG guidelines.
- •Adequate hematopoietic function within 21 days prior to Cycle 1 Day 1 (See Exclusion Criterion #20 for transfusion washout periods for RBCs and platelets):
- •Hemoglobin level ≥ 8.5 g/dL
- •ANC ≥ 1000/mm^3
- •Platelet count ≥ 75,000/mm^3 (patients in whom < 50% of bone marrow nucleated cells are plasma cells) or ≥ 50,000/mm^3 (patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells. [Platelet transfusions < 1 week prior to Cycle 1 Day 1 are prohibited (see below).]
- •Female subjects of child-bearing potential must have both of the following:
- •Agree to the use of two study physician-approved contraceptive methods simultaneously, or practice complete abstinence starting at the time of ICF signature, while on study medication, and 3 months following the last dose of study drug.
- •Have negative serum pregnancy test result at screening.
排除标准
- •The presence of any of the following will exclude a subject from enrollment:
- •Active smoldering MM.
- •Active plasma cell leukemia.
- •Documented systemic amyloid light chain amyloidosis.
- •Active central nervous system (CNS) MM.
- •Pregnancy or breastfeeding.
- •Chemotherapy ≤ 4 week, radiation and immunotherapy ≤ 4 weeks prior to Cycle 1 Day 1, and radio-immunotherapy 6 weeks prior to Cycle 1 Day
- •Active graft vs. host disease (after allogeneic stem cell transplantation) at Cycle 1 Day 1
- •Life expectancy of < 4 months.
- •Major surgery within four weeks prior to Cycle 1 Day
- •Active, unstable cardiovascular function:
- •Symptomatic ischemia, or
- •Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or
- •Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or
- •Myocardial infarction (MI) within 3 months prior to Cycle 1 Day
- •Prior exposure to a SINE compound, including ATG-010.
研究组 & 干预措施
ATG-010 + Dexamethasone
Open-label ATG-010 80mg plus Dexamethasone 20 mg
干预措施: ATG-010 (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 12 months
The primary efficacy endpoint of ORR consists of proportion of patients who achieve PR, VGPR, CR, or sCR according to IMWG 2016 criteria: * CR means Negative IFE of serum and urine, disappearance of any soft tissue plasmacytomas (SPD), and \<5% plasma cells in bone marrow aspirates; * sCR means CR as defined above plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio ≤ 4:1 or ≥ 1:2 for κ and λ patients, respectively, after counting ≥ 100 plasma cells); * VGPR means Serum and urine M-protein detectable by IFE but not on electrophoresis, or ≥90% reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours; * PR means ≥50% reduction of serum M-protein plus reduction in 24-hour urine M-protein by ≥90% or to \<200 mg per 24 hours. If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.
次要结局
- Progression-Free Survival (PFS)(12 months)