Single-cell Dynamic Profiling in Adults With Newly Diagnosed Acute Myeloid Leukemia Treated With Intensive Chemotherapy. A THEMA Study"
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Successful single-cell RNA-Seq (sc-RNA-Seq) assesment
研究概览
简要总结
The detailed molecular and cellular mechanisms underpinning the clinical activity of most chemotherapies in cancers remain incompletely understood. Understanding how these drugs really act is a prerequisite for their rational therapeutic optimization.
Recent observations suggest that early molecular and cellular changes in cancer cells upon chemotherapy exposure may dictate their long-term fate.
We aim to address this question in previously untreated adult Acute Myeloid Leukemia (AML) patients treated with anthracycline/cytarabine association (either as free drugs, '7+3' regimen, or in liposomal formulation, CPX-351) by sequentially sampling peripheral blood during the first course of therapy, and by performing an early bone marrow reassessment. We will apply single cell RNA sequencing and multiparameter flow cytometry to correlate dynamic phenotypic landscapes with clinical outcomes (remission achievement and relapse-free survival).
The study will be carried in two phases. First, a feasibility phase will be carried in the first 20 patients irrespective of the genetic make-up of their leukemic cells to identify the optimal pre-analytical conditions for single-cell transcriptional profiling.
Second, an expansion phase will be carried focusing on two genetically subsets of patients chosen on the basis of their relative abundance and variability of clinical outcome, namely NPM1c-mutated AML (30% of patients, 60% cure rate) and NPM1-wildtype intermediate-risk AML (25% of patients, 40% cure rate), to correlate single-cell fates with remission and with long-term remission-free survival.
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
- •aged ≥18 years old,
- •have a newly diagnosed AML according to WHO criteria
- •o patients with AML related to prior chemotherapy or radiotherapy for another cancer will be eligible,
- •have signed the informed consent form of the e-THEMA observatory trial
- •have ≥10% blasts (blasts+myeloblasts) on the peripheral blood smear at screening,
- •have ≥20% blasts on the bone marrow smear at screening,
- •have not received any treatment for AML except for hydroxyurea and/or 6-mercaptopurine and steroids
- •o Patients having previous treatments for antecedent myeloid neoplasms including hypomethylating agents remain eligible,
- •Eligible to intensive chemotherapy, due to general health status,
- •ECOG performance status ≤ 2,
- •Patient is planned to receive anthracycline (daunorubicin [DNR] or idarubicine [IDA]) - cytarabine 7+3 with or without gemtuzumab ozogamycin (GO) or midostaurine, or CPX-351 as first induction course,
- •Weighing 50 kg or more (compliance to Loi Jardé for PB sampling),
- •Written informed consent obtained prior to any screening procedures,
- •Eligible for National Health Insurance in France.
排除标准
- •Suspected or proven acute promyelocytic leukemia based on morphology, karyotype or molecular assay,
- •Failure to perform bone marrow aspiration at diagnosis,
- •Unstable angina, New York Heart Association (NYHA) class 3 or 4 congestive heart failure,
- •Prior anthracycline exposure more than 360 mg/m²,
- •Previous therapy for AML with any other investigational agent or cytotoxic drug, within 28 days before starting treatment. Only hydroxyurea is permitted for the control of blood counts. Treatments for an antecedent myeloid neoplasm (MDS or MPN) are not considered as exclusion criteria.
- •Women who are pregnant or breastfeeding.
- •Any of concurrent severe and/or uncontrolled medical condition, which could compromise participation in the study.
- •Enrolment in a clinical trial which could compromise participation in the study.
结局指标
主要结局
Successful single-cell RNA-Seq (sc-RNA-Seq) assesment
时间窗: up to 8 days
Successful sc-RNA-Seq assessment is defined as the detection of \> 1000 cells representing \> 50% of the total number of viable loaded cells, with \> 1000 reads per cell
Complete Remission (CR) without MRD
时间窗: End of induction (day 28 to day 56)
次要结局
- Cumulative Incidence of Relapse(at 5 years)
- Overall Survival(at 5 years)
- Event-Free Survival(at 5 years)