A Phase 2 Study of MAX-40279 Combined With Venetoclax and Azacitidine in Unfit Newly Diagnosed Acute Myeloid Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- DLT
研究概览
简要总结
This is a prospective, multicenter, phase Ⅱ study consisting of dose escalation and ex-pansion stages in unfit newly diagnosed AML.
详细描述
This is a prospective, multicenter, phase Ⅱ study consisting of dose escalation and ex-pansion stages in unfit newly diagnosed AML. Patients in dose escalation stage received oral MAX-40279 at three doses, in combination with VEN and AZA in 28-day cycles. Three to six patients were enrolled at each dose level. The dose limiting toxicities (DLTs) observation period was 28 days after the first dose. All evaluable patients with ≥1 cycle treatment were included in preliminary efficacy analysis.
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
- •1. Patients meeting the World Health Organization (WHO) 2016 diagnostic criteria for newly diagnosed acute myeloid leukemia (AML) patients unfit for intensive chemotherapy:
- •Age ≥65 years, or
- •Age >18 years and ineligible for standard-dose chemotherapy, defined by ≥1 of the following:
- •ECOG performance status 2 or 3；History of chronic heart failure (CHF) requiring treatment or left ventricular ejection fraction (LVEF) ≤50% DLCO ≤65% or FEV1 ≤65%Creatinine clearance ≥30 mL/min but ≤45 mL/min (Cockcroft-Gault)、Any other condition deemed incompatible with standard chemotherapy (requires PI approval)
- •No prior AML therapy, except:Hydroxyurea.
- •ECOG performance status ≤3
- •Laboratory requirements: WBC≤3×10*9/L、AST/ALT/ALP ≤3×ULN (except: due to leukemic involvement)、Total bilirubin ≤1.5×ULN、Serum creatinine clearance ≥30 mL/min (measured or calculated)
- •Life expectancy ≥3 months
- •Contraception requirements: Negative pregnancy test for women of childbearing potential；Agreement to use effective contraception during treatment and for 6 months after therapy
排除标准
- •AML with BCR::ABL1 fusion、Acute promyelocytic leukemia (APL).
- •Secondary AML, including:Therapy-related AML (per WHO classification)、AML with prior history of myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN).
- •Use of strong/moderate CYP3A4 inducers within 3 days prior to treatment initiation.
- •Hypersensitivity to any study drugs.
- •Active malignancy in other organs (requiring treatment).
- •Active cardiac disease, defined as ≥1 of the following:Myocardial infarction within 6 months before enrollment；History of symptomatic arrhythmia requiring medication；Uncontrolled/symptomatic congestive heart failure (NYHA Class >2)
- •Active infections, including:Untreated tuberculosis or any aspergillosis.
- •Known HIV, active hepatitis B (HBV), or hepatitis C (HCV).
- •Central nervous system (CNS) leukemia at baseline.
- •Conditions limiting oral drug absorption (e.g., malabsorption syndrome).
- •Medical history of:Epilepsy requiring medication、Dementia or psychiatric disorders impairing protocol compliance.
- •Investigator's discretion for ineligibility.
结局指标
主要结局
DLT
时间窗: Dose escalation; an average of 6 months.
The dose limiting toxicities, Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Adverse events (AEs), serious adverse events (SAEs)
时间窗: Through study completion; an average of 24 months.
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Maximum Tolerated Dose (MTD) or Recommended Phase 2 Dose (RP2D)
时间窗: Dose escalation; an average of 6 months.
Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
CRc
时间窗: Through study completion; an average of 24 months.
complete remission rate
次要结局
- RFS(Through study completion; an average of 8 months.)
- DoR(Through study completion; an average of 8 months.)
- OS(Through study completion; an average of 24 months.)