Investigator-Initiated Phase I/II Clinical Trial of Selinexor (KPT-330) and Liposomal Doxorubicin for Relapsed and Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
The main purpose of this study is to determine the recommended doses of selinexor in combination with liposomal doxorubicin and dexamethasone for patients with relapsed and refractory myeloma. In addition, the study will assess whether this combination with effective for patients with multiple myeloma.
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
- •Patients with relapsed and refractory multiple myeloma who have received at least 2 prior therapies which must include lenalidomide and a proteasome inhibitor. Patients must have disease refractory to the most recent therapy. Refractory myeloma is defined as progressive disease during or within 60 days of last therapy. Patients must have previously received or be ineligible for (or refused) autologous stem cell transplant.
- •Must have measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g excreted in a 24-hour urine collection sample) or by free light chain (involved free light chain greater than 100 mg/L).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •ECOG 2 allowed if due to bone disease
- •Must have an echocardiogram or multigated acquisition (MUGA) scan indicating left ventricular ejection fraction (LVEF) ≥ 50% within 42 days prior to first dose of study drug
- •Adequate hematological function
- •Adequate hepatic function within 14 days prior to loading phase (day -14)
- •Adequate renal function within 14 days prior to loading: estimated creatinine clearance of ≥ 30 mL/min, (Cockcroft and Gault)
- •Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening. Male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.
排除标准
- •Women who are pregnant or lactating
- •Radiation, chemotherapy, or immunotherapy or any other approved anticancer therapy ≤2 weeks prior to day -7 (beginning of loading phase)
- •Major surgery within four weeks before Day -7
- •Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
- •Prior cumulative exposure to doxorubicin (including liposomal preparation) > 350mg/m^2
- •Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; patients with controlled infection or on prophylactic antibiotics are permitted in the study
- •Known to be HIV seropositive
- •Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus (HCV) RNA or HBsAg (HBV surface antigen)
- •Any underlying condition that would significantly interfere with the absorption of an oral medication
- •Grade >2 peripheral neuropathy at baseline (within 14 days prior to loading phase (day -7))
- •Serious psychiatric or medical conditions that could interfere with treatment
- •Participation in an investigational anti-cancer study within 3 weeks prior to day -7(beginning of loading phase)
- •Concurrent therapy with approved or investigational anticancer therapeutic
- •Coagulation problems and active bleeding in the last month
- •Previous allogeneic transplant within 6 months and have evidence of clinically significant graft versus host disease
研究组 & 干预措施
Selinexor, Liposomal Doxorubicin and Dexamethasone
Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D).
After the initial screening visit and registration in the study, participants will receive Selinexor orally at a dose of 80 mg along with dexamethasone for 1 day. One week later, patients will receive weekly selinexor at a starting dose from 60 mg once a week to 80 mg twice a week in combination with pegylated liposomal doxorubicin at a starting dose of 20 mg/m², and dexamethasone 40 mg orally weekly.
干预措施: Selinexor (Drug)
Selinexor, Liposomal Doxorubicin and Dexamethasone
Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D).
After the initial screening visit and registration in the study, participants will receive Selinexor orally at a dose of 80 mg along with dexamethasone for 1 day. One week later, patients will receive weekly selinexor at a starting dose from 60 mg once a week to 80 mg twice a week in combination with pegylated liposomal doxorubicin at a starting dose of 20 mg/m², and dexamethasone 40 mg orally weekly.
干预措施: Liposomal doxorubicin (Drug)
Selinexor, Liposomal Doxorubicin and Dexamethasone
Combination Therapy: Phase I Dose Escalation followed by Phase 2 treatment at Recommended Phase 2 Dose (RP2D).
After the initial screening visit and registration in the study, participants will receive Selinexor orally at a dose of 80 mg along with dexamethasone for 1 day. One week later, patients will receive weekly selinexor at a starting dose from 60 mg once a week to 80 mg twice a week in combination with pegylated liposomal doxorubicin at a starting dose of 20 mg/m², and dexamethasone 40 mg orally weekly.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: Up to 12 months
Determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D): Selinexor on Days 1, 8 and 15 when given in combination with Lipodox 20 mg/m\^2 and Dexamethasone 40 mg. Dose level 1: 40 mg in combination with Lipodox and Dexamethasone. Dose level 2: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone. Dose level 2m: 80 mg (D1,8,15) in combination with Lipodox and Dexamethasone. Dose level 3m: 80 mg (D1,3,8,10) in combination with Lipodox and Dexamethasone.
Overall Response Rate (ORR) -All Participants Treated at Recommended Phase 2 Dose
时间窗: Up to 24 months
Determine the overall response rate per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): \>/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>/= 90% or to \< 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \</= 5% plasma cells in bone marrow.
Overall Response Rate (ORR) - All Participants
时间窗: Up to 24 months
ORR per the modified uniform response criteria of the International Myeloma Working Group (IMWG), partial response and better. Partial Remission (PR): \>/= 50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>/= 90% or to \< 200 mg per 24 hours; Very Good Partial Remission (VGPR): Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours; Complete Remission (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \</= 5% plasma cells in bone marrow. Stable Disease: Not meeting criteria for CR, VGPR, PR, or progressive disease. Minimal response: Less than 50% decrease in M protein. Not evaluable: Cannot be measured because enough information has not been collected.
次要结局
未报告次要终点