An Open-Label, One-Arm, Multi-Site Trial of Precision Diagnosis Directing Target Total Therapy for Adult Ph-like Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Event free survival
研究概览
简要总结
Ph-like ALL is a recently recognized high-risk subgroup and the optimal therapeutic approaches are poorly characterized. Based on the pediatric-inspired, PEG-L-asparaginase-intensified and MRD-directed PDT-ALL-2016 protocol, this open-label, two-arm, multi-site trial PDT-Ph-like-ALL is aimed to evaluate the safety and effect of oral histone deacetylase inhibitor chidamide and dasatinib for adult Ph-like ALL.
详细描述
Ph-like, or BCR-ABL1-like lymphoblastic leukemia is neoplasm of lymphoblasts committed to the B-cell lineage that lack the BCR-ABL1 translocation but show a pattern of the expression very similar to that seen in BCR-ABL1-positive ALL. Chidamide is a novel oral HDACi with promising activity in non-Hodgkin lymphoma (NHL). Based on the pediatric-inspired, PEG-L-asparaginase-intensified and MRD-directed PDT-ALL-2016 protocol, this open-label, two-arm, multi-site trial is aimed to evaluate the safety and effect of oral histone deacetylase inhibitor (HDACi) chidamide and tyrosine kinase inhibitor (TKI) dasatinib for adult Ph-like ALL/LBL. HDACi chidamide and TKI dasatinib will be added to chidamide and dasatinib group, respectively, from induction therapy to consolidation therapy (total courses of chidamide treatment: 5 courses for allo-HSCT after Consolidation Module-3; 12 courses for patients non-allo-HSCT after Consolidation Module 1-9). Primary study endpoint is event-free survival and secondary study endpoints are complete remission and MRD after induction, adverse event and overall survival.
Pretreatment: Dexamethasone, -3 to 0d;
Chidamide for chidamide arm: 10mg/d, po qd.
Dasatinib for Dasatinib arm: 100mg/d, po qd.
Induction:VCR: 1, 8, 15, 22; IDA: 1, 8; CTX: 1g/m2, 1; PEG-asp: 2000-2500IU/m2, 1, 15; Pred: 1-24;
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •14-55 years old;
- •Ph-like ALL newly diagnosed;
- •signed written informed consent
排除标准
- •Pregnant women;
- •History of pancreatitis;
- •History of diabetes;
- •History of active peptic ulcer disease in the past 6 months;
- •History of arteriovenous thrombosis in the past 6 months;
- •Severe active infection;
- •Allergic to any drugs in PDT-Ph-like-ALL.
研究组 & 干预措施
Chidamide
Chidamide will be added to chidamide arm Ph-like ALL(CRLF2 high-expression, CRLF2/EPO/JAK2 rearrangement, JAK/IL-7R/SH2B3 mutation, etc).
干预措施: Chidamide (Drug)
Dasatinib
Dasatinib at a dose of 100mg/day will be added to Dasatinib arm of Ph-like ALL (CRKL high-expression, ABL1 or ABL2 or CSFR1 or PRGFRB rearrangement, etc).
干预措施: Dasatinib (Drug)
结局指标
主要结局
Event free survival
时间窗: 3 years
EFS of Ph-like ALL group
次要结局
- Relapse free survival(3 years)
- Overall survival(3 years)
- CR after Induction Therapy(3 months)
- Death in induction(3 months)
- Adverse events(3 years)
- Relapse(3 years)
- Minimum residual disease after induction(3 months)
研究者
Hongsheng Zhou. M.D., Ph.D
M.D., Professor
Nanfang Hospital, Southern Medical University