A Prospective Single-Arm Clinical Study of Venetoclax Combined With Azacitidine, Chidamide, Vindesine, and Dexamethasone in Newly Diagnosed ETP-ALL Like Patients
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 27
- 试验地点
- 1
- 主要终点
- Composite Complete Remission Rate（CRc） after induction therapy
研究概览
简要总结
ETP-ALL like patients have poor outcomes and prognosis, and the optimal therapeutic approaches are poorly characterized. The goal of this clinical trial is to evaluate the efficacy and safety of the venetoclax combined with azacitidine, chidamide, vindesine, and dexamethasone regimen in newly diagnosed ETP-ALL like patinets (including ETP-ALL, near ETP-ALL and T-ALL with myeloid mutations) .
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
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age: >14 to 65 years (inclusive).
- •Diagnosis: Patients diagnosed with ETP-ALL like disease meeting the following flow cytometry immunophenotypic criteria:
- •ETP-ALL: CD7+, CD1a-, CD8-, CD5 positivity rate ≤75%, and positive for at least one myeloid/stem cell antigen marker (including but not limited to CD34, CD117, HLA-DR, CD13, CD33, CD11b, or CD65); MPO negative.
- •Near-ETP-ALL: CD7+, CD1a-, CD8-, CD5 positivity rate >75%, AND positive for at least one myeloid/stem cell antigen marker (including but not limited to CD34, CD117, HLA-DR, CD13, CD33, CD11b, or CD65); MPO negative.
- •T-ALL with myeloid mutations: FLT3, DNMT3A, STAG2, IDH1/IDH2, RUNX1, EZH2, WT1, ASXL1/ASXL2, SF3B1, TET2, BCOR, BCORL
- •Newly diagnosed patients who have not received any prior induction therapy before enrollment (excluding hydroxyurea, dexamethasone, low-dose cytarabine, venetoclax with a cumulative dose <0.5g, and leukapheresis).
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-
- •Expected survival >6 months.
- •Demonstrated capacity to understand the study and willingness to provide informed consent.
排除标准
- •Pregnancy, breastfeeding, or unwillingness to use contraception in women of childbearing potential
- •Presence of uncontrolled active infection (including bacterial, fungal, or viral infections); concurrent active HBV, HCV, or HIV infection.
- •Severe Organ Dysfunction:
- •Cardiac Insufficiency: Left ventricular ejection fraction (LVEF) ≤40%, OR history of congestive heart failure, unstable coronary artery disease, or severe arrhythmia.
- •Respiratory Failure: Partial pressure of arterial oxygen (PaO₂) ≤60 mmHg. Hepatic Impairment: Total bilirubin ≥2 times the upper limit of normal (ULN), OR alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 times ULN.
- •Renal Impairment: Serum creatinine ≥2 mg/dL, OR creatinine clearance ≤30 mL/min/1.73m².
- •Hypersensitivity: History of hypersensitivity to any of the study drugs or compounds of similar chemical structure.
- •Presence of central nervous system (CNS) leukemia.
- •Any other condition deemed by the investigator to make the subject unsuitable for participation in this trial.
研究组 & 干预措施
Venetoclax Combined with Azacitidine, Chidamide, Vindesine, and Dexamethasone
Induction Therapy Phase:
VACVP induction:Venetoclax: 100mg, d1, 200mg, d2, 400mg, d3-d21, orally. Azacitidine,75mg/m²/day, d1-d7, subcutaneously. Chidamide,10mg, d1-d7, orally. Vindesine, 4mg, d1, intravenous infusion. Dexamethasone,9mg/m²/day, d1-d14; reduced by half on d15-d17; further reduced by half on d18-d21, intravenous infusion or orally.
Consolidation therapy:
- alternate use of HD-MTX-Ara C and VACVP
- allogeneic hematopoietic stem cell transplantation (HSCT)
干预措施: VEN (Venetoclax) (Drug)
Venetoclax Combined with Azacitidine, Chidamide, Vindesine, and Dexamethasone
Induction Therapy Phase:
VACVP induction:Venetoclax: 100mg, d1, 200mg, d2, 400mg, d3-d21, orally. Azacitidine,75mg/m²/day, d1-d7, subcutaneously. Chidamide,10mg, d1-d7, orally. Vindesine, 4mg, d1, intravenous infusion. Dexamethasone,9mg/m²/day, d1-d14; reduced by half on d15-d17; further reduced by half on d18-d21, intravenous infusion or orally.
Consolidation therapy:
- alternate use of HD-MTX-Ara C and VACVP
- allogeneic hematopoietic stem cell transplantation (HSCT)
干预措施: Azacitidine (AZA) (Drug)
Venetoclax Combined with Azacitidine, Chidamide, Vindesine, and Dexamethasone
Induction Therapy Phase:
VACVP induction:Venetoclax: 100mg, d1, 200mg, d2, 400mg, d3-d21, orally. Azacitidine,75mg/m²/day, d1-d7, subcutaneously. Chidamide,10mg, d1-d7, orally. Vindesine, 4mg, d1, intravenous infusion. Dexamethasone,9mg/m²/day, d1-d14; reduced by half on d15-d17; further reduced by half on d18-d21, intravenous infusion or orally.
Consolidation therapy:
- alternate use of HD-MTX-Ara C and VACVP
- allogeneic hematopoietic stem cell transplantation (HSCT)
干预措施: Chidamide (Drug)
Venetoclax Combined with Azacitidine, Chidamide, Vindesine, and Dexamethasone
Induction Therapy Phase:
VACVP induction:Venetoclax: 100mg, d1, 200mg, d2, 400mg, d3-d21, orally. Azacitidine,75mg/m²/day, d1-d7, subcutaneously. Chidamide,10mg, d1-d7, orally. Vindesine, 4mg, d1, intravenous infusion. Dexamethasone,9mg/m²/day, d1-d14; reduced by half on d15-d17; further reduced by half on d18-d21, intravenous infusion or orally.
Consolidation therapy:
- alternate use of HD-MTX-Ara C and VACVP
- allogeneic hematopoietic stem cell transplantation (HSCT)
干预措施: vindesine (Drug)
Venetoclax Combined with Azacitidine, Chidamide, Vindesine, and Dexamethasone
Induction Therapy Phase:
VACVP induction:Venetoclax: 100mg, d1, 200mg, d2, 400mg, d3-d21, orally. Azacitidine,75mg/m²/day, d1-d7, subcutaneously. Chidamide,10mg, d1-d7, orally. Vindesine, 4mg, d1, intravenous infusion. Dexamethasone,9mg/m²/day, d1-d14; reduced by half on d15-d17; further reduced by half on d18-d21, intravenous infusion or orally.
Consolidation therapy:
- alternate use of HD-MTX-Ara C and VACVP
- allogeneic hematopoietic stem cell transplantation (HSCT)
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Composite Complete Remission Rate（CRc） after induction therapy
时间窗: Time from the completion of induction and before consolidation therapy（up to 42 days）
Rates of complete remission (CR), and complete remission with incomplete hematologic recovery (CRi)
次要结局
- MRD(At the end of induction（up to 42 days）, 1 cycle of consolidation（up to 42 days）, 2 cycle of consolidation （up to 42 days）and the end of consolidation（up to 42 days）)
- Overall survival（OS）(2 years)
- duration of remission (DOR)(2 years)
- AE(Within 30 days after the last chemotherapy)
- Relapse-Free Survival(RFS)(2 years)