Phase Ib/II Study of ATG-010 in Combination With Thalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
Multiple myeloma (MM) is an incurable plasma cell cancer that almost all patients eventually relapse despite advancement in treatment strategies. B-cell maturation antigen (BCMA) is a cell surface receptor that expressed primarily by malignant and normal plasma cells. This is a single-arm that includes escalation phase and expansion phase ,Selinexor in Combination withThalidomide and Dexamethasone to Treat Relapsed/Refractory Multiple Myeloma Patients.To evaluate efficacy and safety of Selinexor in combination with Thalidomide and Dexamethasone in RRMM patients received at least one prior lines of therapy
详细描述
This is a single-arm and open-label phase Ib/IIa study of Relapsed/Refractory Multiple Myeloma patients who have received at least one prior lines of treatment therapy; Approximately 3-48 patients will be enrolled in the study. In dose escalation phase, patients with RRMM will be treated with thalidomide 100mg/d, dexamethasone 20mg biweekly, and escalating doses of oral ATG-010 weekly in a 3+3 design. ATG-010 dose level (DL) 1, 2 and 3 are 60, 80 and 100mg respectively.
Then a phase 2 expansion at the recommended dose level based on phase 1b trial will be conducted to evaluate the efficacy, safety and tolerability.
This arm is 4 weeks per cycle and include a total of 12 cycles.Selinexor RP2D，Thalidomide will be given at 100mg/d d1-28, and Dexamethasone 20 mg/d will be given on day 1, 2,8,9,15,16,22,23. If a patient develops partial intolerance to glucocorticoids (as determined by the Investigator) during the study, a dose reduction of dexamethasone maximum to 10 mg is permitted. If patients do not tolerate this dose, a potential discontinuation or further dose reduction would be allowed.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:
- •Known and written informed consent (ICF) voluntarily.
- •Age ≥ 18 years and ≤ 75 years.
- •Patients with multiple myeloma who have received first-line treatment (induction, autologous transplantation and maintenance as the same first-line treatment) and achieved at least partial remission in induction.
- •At or after accepting first-line regimen, subjects must have progression disease (PD) recorded which is determined by researcher according to IMWG criteria.
- •Any clinically significant non-hematological toxicities (except for hair loss, peripheral neuropathy, which is otherwise stipulated in Article 13 of the exclusion criteria) that relevant to previous therapies must have resolved to ≤Grade 2 prior to first dose of study drug.
- •Adequate hepatic function: total bilirubin < 2× upper limit of normal (ULN) (for patients with Gilbert's syndrome, a total bilirubin of < 3× ULN is required), AST < 2.5× ULN, and ALT < 2.5× ULN.
- •Adequate renal function: estimated creatinine clearance ≥ 20 mL/min (calculated using the formula of Cockroft-Gault).
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or
- •Measurable MM as defined by at least one of the following:
- •Serum M-protein (SPEP) ≥ 10 g/L
- •24 hours-Urinary M-protein excretion ≥ 0.2 g (200 mg)
- •Serum FLC ≥ 100 mg/L with abnormal FLC ratio
- •Expected survival is more than 6 months.
- •Adequate hematopoietic function (no blood transfusion within 2 weeks and no G-CSF/GM-CSF supportive treatment within 1 week prior to screening test):
- •Hemoglobin level ≥ 80 g/L
- •ANC ≥ 1,000/mm3 (1.0×109/L)
- •Platelet count ≥ 75,000/mm3 (75×109/L)
- •Female patients of childbearing potential must meet below two criteria:
- •must agree to use effective contraception methods since signature in ICF, throughout the study and for 3 months following the last dose of study treatment.
- •must have a negative serum pregnancy test at screening. Note: A woman is considered of childbearing potential following menarche and until becoming postmenopausal (defined as no menstrual period for a minimum of 12 months) or permanently sterile (having undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy). A woman who is taking oral contraceptive or using intrauterine device is considered of childbearing potential.
- •Male patients (including those who have received vasectomy) must use a condom if sexually active with a female of child-bearing potential throughout the study and for 3 months following the last dose of study treatment.
排除标准
- •Patients who meet any of the following criteria will not be enrolled:
- •Asymptomatic (smoldering) MM.
- •Plasma cell leukemia.
- •Documented active amyloidosis.
- •Previously refractory or intolerant to immunomodulators.
- •Pregnancy or breastfeeding.
- •Major surgery was performed within 4 weeks prior to the first study.
- •Patients with active, unstable cardiovascular diseases, fits any of the following:
- •Symptomatic ischemia, or
- •Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with first-degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) are allowed), or
- •Congestive heart failure (CHF) of New York Heart Association (NYHA) ≥ Grade 3, or
- •Acute myocardial infarction (AMI) within 3 months prior to the first dose of study drug.
- •Uncontrolled active infection within 1 week prior to the first dose of study drug.
- •Known HIV positive.
- •Known active hepatitis A, B, or C infection; or known positive for HCV RNA or HBsAg.
- •(Note: patients with HBsAg negative but HBc Ab positive need further HBV-DNA test, excluded if HBV-DNA ≥103 , if HBV-DNA <103 need anti-viral drugs)
- •Prior malignancy that required treatment or has shown evidence of recurrence (except for skin basal-cell carcinoma and in-situ carcinoma including squamous cell carcinoma, bladder cancer in situ, endometrial cancer in situ, cervical cancer in situ/atypical hyperplasia, prostate cancer incidental finding (T1a or T1b), or breast cancer in situ) within 5 years prior to the first dose of study drug.
- •Active GI dysfunction interfering with the ability to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment.
- •Grade ≥ 3 peripheral neuropathy, and Grade ≥ 2 painful neuropathy, within 3 weeks prior to the first dose of study drug.
- •Previous history of deep vein thrombosis.
- •Serious, active psychiatric, or medical conditions which, in the opinion of the Investigator, could interfere with study treatment.
- •Participation in an investigational anti-cancer clinical study within 3 weeks or 5 half-lives (T1/2) prior to the first dose of study drug.
- •Received ASCT within 12 weeks prior to the first dose of study drug or previous allogeneic stem cell transplantation (no time limitation).
- •Treatment with an approved or trial anticancer drug was given within 4 weeks prior to the first study.
- •Known intolerance to or contraindication for glucocorticoid therapy.
- •Prior exposure to a SINE compound.
研究组 & 干预措施
Selinexor in combination with thalidomide and Dexamethasone
Selinexor in combination with thalidomide and Dexamethasone. Thalidomide will be given at 100mg/d d1-28,and Dexamethasone 20 mg/d will be given on day 1, 2,8,9,15,16,22,23. Treatment will be administered in 28-day cycles,include a total of 12 cycles. Selinexor dose escalation: 60, 80, 100mg respectively on day 1,8,15,22 for 4-week cycles. Then Selinexor will be given at the recommended dose level on phase II.
干预措施: Selinexor (Drug)
Selinexor in combination with thalidomide and Dexamethasone
Selinexor in combination with thalidomide and Dexamethasone. Thalidomide will be given at 100mg/d d1-28,and Dexamethasone 20 mg/d will be given on day 1, 2,8,9,15,16,22,23. Treatment will be administered in 28-day cycles,include a total of 12 cycles. Selinexor dose escalation: 60, 80, 100mg respectively on day 1,8,15,22 for 4-week cycles. Then Selinexor will be given at the recommended dose level on phase II.
干预措施: Thalidomide (Drug)
Selinexor in combination with thalidomide and Dexamethasone
Selinexor in combination with thalidomide and Dexamethasone. Thalidomide will be given at 100mg/d d1-28,and Dexamethasone 20 mg/d will be given on day 1, 2,8,9,15,16,22,23. Treatment will be administered in 28-day cycles,include a total of 12 cycles. Selinexor dose escalation: 60, 80, 100mg respectively on day 1,8,15,22 for 4-week cycles. Then Selinexor will be given at the recommended dose level on phase II.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: Assessed from the date of first dose of study treatment until the date that PD assessed up to 12months
ORR in each arm: partial response (PR) + very good partial response (VGPR) + complete response (CR)
次要结局
- Disease Control Rate (DCR)(12 months)
- Duration of Response (DOR)(12 months)
- Overall Survival (OS)(12 months)
- Minimal Residual Disease (MRD)(12 months)
- Progression-Free Survival (PFS)(12 months)
- Clinical Benefit Rate (CBR)(12 months)
- Number of Participants with Adverse Events(From first dose of study drug administration to end of treatment (up to 12 months))
研究者
Li Zheng
Chief physician, professor
Sichuan University