Clinical Efficacy and Safety of Selinexol Combined With Azacitidine and Venetoclax (SAV Regimen) in the Treatment of Acute Myeloid Leukemia (AML)-a Multi-center, Single-arm, Prospective Clinical Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 58
- 试验地点
- 19
- 主要终点
- Percentage of Participants With Composite Complete Remission
研究概览
简要总结
This is a prospective, single-arm, multi-center clinical trial to evaluate the efficacy and safety of selinexor in combination with azacitidine and venetoclax for untreated acute myeloid leukemia.
详细描述
This is a prospective, single-arm, multi-center clinical trial to evaluate the efficacy and safety of selinexor in combination with azacitidine and venetoclax for untreated acute myeloid leukemia.
Selinexor will be given orally at 60mg, d3,10,17 Azacitidine will be given at 75mg/m2, d1-3, 8-9, 15-16 Venetoclax will be given orally at 100mg on day 1 and 200mg on day 2, 400mg on day 3-14
28 days per cycle, patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive treatment until disease progression or unacceptable toxic effects.
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
- •Known and written informed consent voluntarily
- •Age ≥ 18 years
- •Newly diagnosed AML patients (per WHO 2022 classification criteria for AML diagnosis), who are not suitable for intensive chemotherapy:
- •≥75 years or
- •Aged 18 to 74 years with at least one of the following comorbidities: Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or 3 or 4; Cardiac history of Congestive Heart Failure (CHF) requiring treatment or Ejection Fraction <= 50% or chronic stable angina; Diffusing capacity of the Lung for Carbon Monoxide (DLCO) <= 65% or Forced Expiratory Volume in 1 second (FEV1) <= 65%; Creatinine clearance >= 30 mL/min to < 45 ml/min; Moderate hepatic impairment with total bilirubin > 1.5 to <= 3.0 × Upper Limit of Normal (ULN); Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy .
- •patients who are suitable for intensive chemotherapy but refuse it
- •Liver function meets the following criteria:
- •aspartate aminotransferase (AST) ≤ 3.0×ULN*; alanine aminotransferase (ALT) ≤ 3.0×ULN*; Bilirubin≤1.5×ULN*; For subjects <75 years old, the bilirubin level can be ≤3.0×ULN;
- •Unless due to leukemic organ involvement.
- •Renal function meets the following criteria: creatinine clearance ≥ 30 mL/min (Cockroft-Gault formula)
- •Life expectancy ≥ 4 weeks
排除标准
- •History of any malignancies prior to study entry with exception noted in the protocol.
- •Participant has known HIV infection, active hepatitis B virus (HBV) and/or hepatitis C virus (HCV) .
- •Participant has known active central nervous system (CNS) involvement with AML.
- •Must not have received prior anti-AML treatment except for hydroxyurea
研究组 & 干预措施
SAV arm
Untreated acute myeloid leukemia who are ineligible for intensive chemotherapy or who refuse to receive intensive chemotherapy will receive selinexor in combination with azacitidine and venetoclax, 28 days per cycle, patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive SAV regimen until disease progression or unacceptable toxic effects.
干预措施: Selinexor (Drug)
SAV arm
Untreated acute myeloid leukemia who are ineligible for intensive chemotherapy or who refuse to receive intensive chemotherapy will receive selinexor in combination with azacitidine and venetoclax, 28 days per cycle, patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive SAV regimen until disease progression or unacceptable toxic effects.
干预措施: Azacitidine (Drug)
SAV arm
Untreated acute myeloid leukemia who are ineligible for intensive chemotherapy or who refuse to receive intensive chemotherapy will receive selinexor in combination with azacitidine and venetoclax, 28 days per cycle, patients can receive transplants at any time once they achieved complete remission and other patients will continue to receive SAV regimen until disease progression or unacceptable toxic effects.
干预措施: Venetoclax (Drug)
结局指标
主要结局
Percentage of Participants With Composite Complete Remission
时间窗: From the study start up to death (up to approximately 2 years; )
composite complete remission(CR , CRh, CRi) was calculated based on ELN2022 criteria.
次要结局
- Overall response rate(ORR)(From the study start up to death (up to approximately 4 years; ))
- Recurrence Free Survival(RFS)(From the study start up to death (up to approximately 4 years; ))
- overall survival (OS)(From the study start up to death (up to approximately 4 years; ))
- percentage of patients who achieved MRD negativity(From the study start up to death (up to approximately 4 years; ))
研究者
Liu Ligen
Director
Shanghai Tong Ren Hospital