An Open Label, Single Arm, Single-Center Exploratory Study to Evaluate the Efficacy and Safety of Selinexor and HAAG +/- HMA in Relapsed/Refractory Acute Leukemia (AML) Patients
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of Participants With CR/CRi
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of selinexor and HAAG +/- HMA in relapsed/refractory acute leukemia (AML) patients.
详细描述
This protocol corresponds to a single-center, open-label, single-arm, exploratory study designed to determine the efficacy and safety of the combination of selinexor with HAAG +/- HMA in patients with relapsed or refractory AML. The patients who respond to this combination treatment will undergo allogeneic hematopoietic stem cell transplantation and post-transplantation maintenance treatment according to patient's wishes.
Each cycle of treatment will compromise 2 weeks of selinexor treatment, and at least two weeks off treatment. The new cycle will not start if there is an ongoing grade 3 or higher non-hematologic toxicity or persistent grade 3 neutropenia in patients achieving CR.
Study design allows 20 patients. Treatment will consist of selinexor 60 mg/day orally on d1,4,8,11, HHT 1 mg/day intravenously on days 3 to 9, cytarabine 10 mg/m2 q12h, intravenously on days 3 to 9, aclacinomycin 10 mg/day intravenously on days 3 to 6, G-CSF 50-600 mcg/m2/day intravenously from days 2 to start, this dosage will be adjusted according to the hemogram, DAC 20 mg/m2/day intravenously on days 1 to 5. Whether to add hypomethylating agents was decided by the investigator according to the patient's disease degree and tolerance status. If patients had previously been exposed to decitabine, azacitidine will added this regimen, AZA 20 mg/m2/day subcutaneously on days 1 to 7.
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
- •Men and women aged ≥18 years.
- •Diagnosis of AML (defined according to the 5th of the World Health Organization [WHO] 2022 criteria) of any type except for acute promyelocytic leukemia (APL; AML M3)and the following conditions were met: Relapsing or refractory AML
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤
- •Female patients of child-bearing potential must have a negative serum pregnancy test at screening and agree to use two reliable methods of contraception for six months after their last dose of medication.
- •Patients whose expecting survival time will be more than 3 months.
- •Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other study procedures.
排除标准
- •AML transformed from chronic myeloid leukemia.
- •Patients with APL/AML M
- •Presence of CNS leukemia.
- •Uncontrolled infection or other serious disease.
- •Unstable cardiovascular function: Cardiac ejection fraction (EF)<0.5, or congestive heart failure (CHF) of NYHA Class ≥
- •Unstable Liver and kidney function:TBLL≥2.0 mg/dl, AST≥3×ULN, Ccr≥50 ml/min, SpO2<92%.
- •Known human immunodeficiency virus (HIV) infection.
- •Active hepatitis B or hepatitis C infection.
- •Pregnant and lactating women. Patients with other commodities that the investigators considered not suitable for the enrollment.
研究组 & 干预措施
Selinexor+HAAG±HMA
干预措施: Selinexor (Drug)
Selinexor+HAAG±HMA
干预措施: Homoharringtonine (Drug)
Selinexor+HAAG±HMA
干预措施: Cytarabine (Drug)
Selinexor+HAAG±HMA
干预措施: Aclacinomycin (Drug)
Selinexor+HAAG±HMA
干预措施: Granulocyte Colony-Stimulating Factor (Drug)
Selinexor+HAAG±HMA
干预措施: Decitabine (Drug)
Selinexor+HAAG±HMA
干预措施: Azacitidine (Drug)
结局指标
主要结局
Number of Participants With CR/CRi
时间窗: End of cycle 1 and 2 (each cycle is 28 days)
Number of Participants With CR/CRi CR: Absolute Neutrophil count (ANC) \>1.0x10\^9/L, Platelet count \>100x10\^9/L, Bone marrow blasts \<5%, no Auer rods, no evidence of extramedullary disease. CRi: Same as CR, but ANC may be \<1.0x10\^9/L and/or Platelet count \<100x10\^9/L
次要结局
- Number of Participants With ORR(End of cycle 1 and 2 (each cycle is 28 days))
- Progression-Free Survival(Time from registration to event, max 2 years)
- Overall Survival(Time from registration to event, max 2 years)
- Number of adverse events(End of cycle 1 and 2 (each cycle is 28 days))
- Percentage of Patients Transplanted After Induction Therapy (Stem Cell Transplantation)(1-2 induction cycles (4 - 8 weeks))