The Efficacy and Safety of Third Generation Tyrosine Kinase Inhibitors Combined With Azacitidine and B-cell Lymphoma-2 Inhibitor in Patients With Myeloid Blast Phase Chronic Myeloid Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 15
- 主要终点
- Major hematologic response (MaHR)
研究概览
简要总结
This is a prospective multi-center study to investigate efficacy and safety of the third generation tyrosine kinase inhibitors (TKIs) combined with azacitidine and B-cell lymphoma-2 (Bcl-2) inhibitor in patients with myeloid blast phase chronic myeloid leukemia (CML-MBP).
详细描述
CML-MBP has dismal outcome. Currently, there is no standardized induction treatment approach in CML-MBP. The European LeukemiaNet (ELN) recommendations and NCCN guideline recommended the combination of TKI and chemotherapy in CML-MBP. The previous study revealed that TKI combined with hypomethylating agents had promising efficacy. However, imatinib and second generation TKI are the most widely applied in combination treatment, there is limited data in third generation TKI.
Currently, venetoclax in combination with hypomethylating agents such as azacitidine is standard treatment for patients with AML unsuitable for intensive induction chemotherapy. Maiti et al. reported that TKI combined with venetoclax and detectable had promising efficacy in CML-MBP. Therefore, the investigator conducted a study to explore the efficacy and safety of a third generation TKI in combination with azacitidine and Bcl-2 inhibitor in CML-MBP and multi-omics exploratory analysis was performed to identify potential biomarkers correlated with the outcome.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •age ≥ 18 years old;
- •philadelphia chromosome (Ph)-positive or BCR::ABL-positive;
- •serum creatinine ≤ 1.5 × upper limit of normal (ULN) or 24h creatinine clearance ≥ 50 mL/min when serum creatinine was > 1.5 × ULN;
- •serum total bilirubin ≤ 1.5 × ULN;
- •aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN;
- •amylase ≤ 1.5 × ULN; (7) lipase ≤ 1.5 × ULN;
- •ejection fraction > 50%; corrected QT interval on electrocardiographic evaluation was ≤ 450 ms in men or ≤ 470 ms in women.
排除标准
- •concurrent diseases requiring treatment(s) with potential to interact with 3G-TKI;
- •diagnosis of other primary malignancies;
- •history of allogeneic HSCT;
- •extramedullary disease only.
研究组 & 干预措施
3G-TKI + AZA + Ven group
Adult CML-MBP
干预措施: Ponatinib (Drug)
3G-TKI + AZA + Ven group
Adult CML-MBP
干预措施: Azacitidine (Drug)
3G-TKI + AZA + Ven group
Adult CML-MBP
干预措施: Venetoclax (Drug)
3G-TKI + AZA + Ven group
Adult CML-MBP
干预措施: Olverembatinib (Drug)
结局指标
主要结局
Major hematologic response (MaHR)
时间窗: At the end of Cycle 2 (each cycle is 28 days)
either a complete hematologic response (CHR) or no evidence of leukemia (NEL).
次要结局
- Return to chronic phase(At the end of Cycle 2 (each cycle is 28 days))
- Major molecular response (MMR)(Up to 3 years)
- Survival(Up to 3 years)
- Major cytogenetic response (MCyR)(Up to 3 years)
- Event-free survival (EFS)(Up to 3 years)
- CML-related survival(Up to 3 years)
- Incidence of adverse events(Up to 3 years)
- Complete cytogenetic response (CCyR)(Up to 3 years)
研究者
Qian Jiang
Professor
Peking University People's Hospital