A Phase 2b, Open-label, Multi-arm Clinical Trial of Selinexor Plus Low-dose Dexamethasone (Sd) in Patients With Penta-refractory Multiple Myeloma or Selinexor and Bortezomib Plus Low-dose Dexamethasone (SVd) in Patients With Triple-class Refractory Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 127
- 试验地点
- 30
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to assess the efficacy, antitumor activity, safety and tolerability of selinexor plus low-dose dexamethasone in participants with penta-refractory multiple myeloma or selinexor and bortezomib plus low-dose dexamethasone in participants with triple-class refractory multiple myeloma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age greater than or equal to (>=)18 years at the time of signing informed consent.
- •Written informed consent in accordance with federal, local, and institutional guidelines.
- •Measurable MM based on IMWG guidelines as defined by at least one of the following:
- •Serum M-protein >= 0.5 gram per deciliter (g/dL) by serum protein electrophoresis (SPEP) or, for Immunoglobulin (Ig) A myeloma, by quantitative IgA.
- •Urinary M-protein excretion >= 200 mg/24 hours.
- •Free light chain (FLC) >= 100 milligram per liter (mg/L), provided that the FLC ratio is abnormal.
- •Only for arms Sd-40 BIW, Sd-100 QW and Sd-80 BIW prior to protocol version (PV) 5.0: Participants must have relapsed or refractory multiple myeloma (RRMM) and have previously received at least 4 anti-MM prior therapies and have MM that is refractory to previous treatment with at least 2 proteasome inhibitors (PIs), at least 2 immunomodulatory agent (IMiDs), and 1 anti-cluster of differentiation (CD38) monoclonal antibody. Refractory is defined as lesser than or equal to (<=) 25 percent (%) response to therapy, or progression during therapy or progression within 60 days after completion of therapy.
- •Only for Arms Sd-40 BIW and Sd-100 QW as of PV 5.0: Participants must have RR MM and have been previously treated with >=3 anti-MM therapies (with exposure to at least 2 PI drugs, at least 2 IMiDs, and 1 anti-CD38 monoclonal antibody), and be refractory to at least 1 drug of each class (PI/IMiD/anti-CD38). Refractory is defined as <=25% response to therapy or progression during therapy or progression within 60 days after completion of therapy.
- •Only for arm SVd: Participants must have previously received 1 to 5 anti-MM prior therapies and have MM that is refractory to previous treatment with at least 1 PI, at least 1 IMiD, and 1 anti- CD38 monoclonal antibody.
- •Eastern Cooperative Oncology Group (ECOG) performance status of <=
- •Female participants of childbearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male participants must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for 7 months for female and 4 months for male following the discontinuation of study treatment.
排除标准
- •Active plasma cell leukemia.
- •Documented systemic amyloid light chain amyloidosis.
- •Active central nervous system MM.
- •Only for SVd arm: Greater than Grade 2 peripheral neuropathy or Grade >= 2 peripheral neuropathy with pain at baseline, regardless of whether or not the participant is currently receiving medication.
- •Radiation, chemotherapy, immunotherapy, or any other anticancer therapy (including investigational therapies) <= 2 weeks prior to Cycle 1 Day 1 (C1D1). (Steroids are permitted up to 1 pulse of 40 mg per day for 4 days in the 2 weeks prior to C1D1).
- •Active graft vs. host disease (after allogeneic stem cell transplantation) at C1D
- •Ongoing clinically significant non-hematological toxicities from prior treatments that are Grade greater than (>) 2 at C1D
- •Inadequate hepatic function defined as total bilirubin >= 2x upper limit of normal (ULN) (>= 3x ULN for participants with Gilbert's syndrome), aspartate transaminase (AST) >= 2.5x ULN, and alanine transaminase (ALT) >= 2.5x ULN.
- •Inadequate renal function defined as estimated creatinine clearance of lesser than (<) 20 milliliter per minute (mL/min), calculated using the formula of Cockroft and Gault.
- •Inadequate hematopoietic function defined as the following:
- •Absolute neutrophil count (ANC) < 1000/cubic millimeter (mm^3)
- •Platelet count < 75,000/mm^3
- •Hemoglobin (Hb) level < 8.5 g/dL
- •Life expectancy of < 4 months, based on the opinion of the Investigator.
- •Major surgery within 4 weeks prior to C1D
- •Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to first dose.
- •Active gastrointestinal dysfunction interfering with the ability to swallow tablets, or any gastrointestinal dysfunction that could interfere with absorption of the study treatment.
- •Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus RNA or hepatitis B virus surface antigen.
- •Female participants who are pregnant or lactating.
- •Known intolerance, hypersensitivity, or contraindication to glucocorticoid therapy at C1D
- •Concurrent therapy with approved or investigational anticancer therapeutic including topical therapies.
- •Prior exposure to a SINE compound, including selinexor.
- •Serious, active psychiatric or active medical conditions which, in the opinion of the Investigator or the Sponsor, could interfere with the participation in the study.
- •Contraindication to any of the required concomitant drugs or supportive treatments.
研究组 & 干预措施
Selinexor + Low-dose Dexamethasone (Sd-40 BIW)
Participants will receive fixed dose of 40 milligram (mg) of Selinexor oral tablet followed by 20 mg of low-dose Dexamethasone oral tablet twice weekly (BIW) on Days 1, 3, 8, 10, 15, 17, 22, and 24 of each 28-day cycle.
干预措施: Selinexor (Drug)
Selinexor + Low-dose Dexamethasone (Sd-40 BIW)
Participants will receive fixed dose of 40 milligram (mg) of Selinexor oral tablet followed by 20 mg of low-dose Dexamethasone oral tablet twice weekly (BIW) on Days 1, 3, 8, 10, 15, 17, 22, and 24 of each 28-day cycle.
干预措施: Dexamethasone (Drug)
Selinexor + Low-dose Dexamethasone (Sd-100 QW)
Participants will receive fixed dose of 100 mg of Selinexor oral tablet followed by 40 mg of low-dose Dexamethasone oral tablet once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle. (Dexamethasone may be given as 20 mg on days 1 and 2 of each week at the discretion of the treating physician).
干预措施: Selinexor (Drug)
Selinexor + Low-dose Dexamethasone (Sd-100 QW)
Participants will receive fixed dose of 100 mg of Selinexor oral tablet followed by 40 mg of low-dose Dexamethasone oral tablet once weekly (QW) on Days 1, 8, 15, and 22 of each 28-day cycle. (Dexamethasone may be given as 20 mg on days 1 and 2 of each week at the discretion of the treating physician).
干预措施: Dexamethasone (Drug)
Selinexor + Low-dose Dexamethasone (Sd-80 BIW)
Participants will receive fixed dose of 80 mg of Selinexor oral tablet followed by 20 mg of low-dose Dexamethasone oral tablet BIW on Days 1, 3, 8, 10,15, 17, 22, and 24 of each 28-day cycle. Closed for recruitment.
干预措施: Selinexor (Drug)
Selinexor + Low-dose Dexamethasone (Sd-80 BIW)
Participants will receive fixed dose of 80 mg of Selinexor oral tablet followed by 20 mg of low-dose Dexamethasone oral tablet BIW on Days 1, 3, 8, 10,15, 17, 22, and 24 of each 28-day cycle. Closed for recruitment.
干预措施: Dexamethasone (Drug)
Selinexor + Bortezomib + Dexamethasone (SVd)
Participants will receive fixed dose of 100 mg of Selinexor oral tablet on Days 1, 8, 15, 22, and 29 followed by 1.3 milligram per square-meter (mg/m^2) of Bortezomib subcutaneous (SC) injection on Days 1, 8, 15, and 22 and followed by 40 mg of low-dose Dexamethasone oral tablet on Days 1, 8, 15, 22, and 29 of each 35-day cycle (Dexamethasone dose may be split to 20 mg on days 1 and 2 of each week at the discretion of the treating physician). Closed for recruitment.
干预措施: Selinexor (Drug)
Selinexor + Bortezomib + Dexamethasone (SVd)
Participants will receive fixed dose of 100 mg of Selinexor oral tablet on Days 1, 8, 15, 22, and 29 followed by 1.3 milligram per square-meter (mg/m^2) of Bortezomib subcutaneous (SC) injection on Days 1, 8, 15, and 22 and followed by 40 mg of low-dose Dexamethasone oral tablet on Days 1, 8, 15, 22, and 29 of each 35-day cycle (Dexamethasone dose may be split to 20 mg on days 1 and 2 of each week at the discretion of the treating physician). Closed for recruitment.
干预措施: Dexamethasone (Drug)
Selinexor + Bortezomib + Dexamethasone (SVd)
Participants will receive fixed dose of 100 mg of Selinexor oral tablet on Days 1, 8, 15, 22, and 29 followed by 1.3 milligram per square-meter (mg/m^2) of Bortezomib subcutaneous (SC) injection on Days 1, 8, 15, and 22 and followed by 40 mg of low-dose Dexamethasone oral tablet on Days 1, 8, 15, 22, and 29 of each 35-day cycle (Dexamethasone dose may be split to 20 mg on days 1 and 2 of each week at the discretion of the treating physician). Closed for recruitment.
干预措施: Bortezomib (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: From the date of randomization up to death (approximately 60 months)
次要结局
- Duration of Response (DOR)(From the date of randomization to first disease progression or death (approximately 60 months))
- Clinical Benefit Rate (CBR)(From the date of randomization up to death (approximately 60 months))
- Disease control rate (DCR)(From the date of randomization up to death (approximately 60 months))
- Progression-Free Survival (PFS)(From the date of randomization to first disease progression or death (approximately 60 months))
- Overall Survival (OS)(From the date of randomization up to death (approximately 60 months))
- Time to Next Treatment (TTNT)(From the date of first dose up to death (approximately 60 months))
- Number of Participants with Adverse Events (AE)(From start of study drug administration up to follow-up (approximately 60 months))