Recruiting
Phase 2
Clinical Study of Induction Therapy Options Based on Molecular Subtyping and MRD in Children and Adolescents With AML
Condition(s) studied
AML, ChildhoodAcute Myeloid Leukemia
Investigational drug(s) / intervention(s)
Homoharringtonine: 3mg/m2/day for weighing \>10kg, 0.1mg/kg/day for weighing ≤10kg, d1-7, ivgtt, qd, more than 6 hours
Cytarabine: 100mg/m2/q12h for weighing \>10kg, 3.3mg/kg/q12h for weighing ≤10kg, d1-7, ivgtt, q12h, more than 30 minutes in SDC group; 10mg/m2/q12h for weighing \>10kg, 0.33mg/kg/q12h for weighing ≤10kg, d1-10, s.c.,q12h (the first dose at 8 am) in the LDC group;
Etoposide: 100mg/m2/d for weighing \>10kg, 3.3mg/kg/d for weighing ≤ 10kg, d1-5, ivgtt, qd, more than 4 hours
Venetoclax: 100mg/m2/d for weighing \>10kg, 3.33mg/kg/d for weighing ≤10kg, d12-25, po, qd
Mitoxantrone hydrochloride liposome: 5mg/m2/d for weighing \>10kg, 0.17mg/kg/d for weighing ≤ 10kg, d1, 3, 5, ivgtt, qod, more than 2 hours at 10 am.
Recombinant Human Granulocyte Colony-Stimulating Factor: 5ug/kg/d, d1-10, s.c., qd, at 1pm
Idarubicin Hydrochloride: 3mg/m2/day for weighing \>10kg, 0.1mg/kg/day for weighing ≤ 10kg, d1-7, ivgtt, qd, more than 6 hours.
Sorafenib: 100mg/m2/day for weighing \>10kg, 3.3mg/kg/day for weighing ≤10kg, from identification, po, qd
Gilteritinib: 20mg/m2/day for weighing \>10kg, 0.7mg/kg/day for weighing ≤ 10kg, from identification, po, qd
Avapritinib: 50mg/m2/day for weighing bodyweight \>10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd
Study summary
The goal of this clinical trial is to estimate the rate (probability) of complete remission or complete remission with incomplete count recovery (CR/CRi) with negative MRD after induction I and II, event-free survival (EFS), and cumulative incidence (probability) of relapse (CIR), in patients receiving molecular/precision medicine and MRD-driven remission inductions, and to assess secondarily if there is an improvement over the AML2018 protocol.
Eligibility
Inclusion Criteria:
* 1、Newly diagnosed, untreated AML；
* 2、Under 18 years old;
* 3、Patients who have used hydroxyurea or cytarabine before diagnosis, but the dosage of cytarabine does not exceed 5 days, and the total dose does not exceed 500 mg/m2 (50 mg/m2, q12h × 5d)；
* 4、 Liver function：Tbil≤2×ULN, ALT/AST≤3×ULN, creatinine clearance ≥50ml/min；Cardiac NYHA grading\<3；SaO2\>92%;
* 5、No active infection (symptoms resolved for more than 3 days if infected)
* 6、ECOG\<2;
* 7、Expected survival time greater than 12 weeks;
* 9、Obtain the consent of the child and/or guardian and sign the informed consent form.
Exclusion Criteria:
* 1、Acute megakaryocytic leukemia (AMKL)；
* 2、Acute promyelocytic leukemia (APL);
* 3、Treatment-related secondary AML and AML with definite MDS transformation；
* 4、Myeloproliferative neoplasm (such as Juvenile myelomonocytic leukemia, JMML);
* 5、AML secondary to congenital bone marrow failure (such as AML secondary to Fanconi anemia (FA)；
* 6、AML secondary to Down syndrome;
* 7、Only temporary chemotherapy, radiotherapy, or immunotherapy, but not systematic treatment according to the treatment plan;
* 8、 Temporary chemotherapy, radiotherapy, or immunotherapy only, not systemic therapy per protocol;
* 9、Having any significant abnormal concurrent disease or mental illness that impacts the life safety and compliance of the patient and impacts informed consent, study participation, follow-up, or interpretation of results. In this case, all the participating units are required to report directly to the responsible person for this project to jointly decide whether they meet the exclusion criteria；
* 10、Patients with very poor nutritional status, severe infection, cardiac insufficiency, and intolerance to chemotherapy;
* 11、Relapsed AML at any time；
* 12、The attending physician considers that the patient is not suitable for entering the study protocol based on the patient's physical condition, economic status, and other factors.
Primary outcome measure(s)
- Rate of CR/CRi with negative MRD — Day 26 (HAE group) and Day 32 (MAG+Ven group) for remission induction 1 and 2 are the necessary time points for response evaluation.
CR/CRi with negative MRD was defined as less than 5% blasts in bone marrow and MRD \<0.1%.
- Event-free survival — From date of treatment until the date of the occurrence of the event, whichever comes first, assessed up to 72 months. Patients remaining event-free are censored at the last follow-up time.
Events/failures of EFS include any-cause death, relapse, second malignancy, no CR after Indiction II and off-therapy due to abandonment or attending physician's decision.
Induction II and off-therapy due to abandonment or attending physician's decision.
- Cumulative incidence of relapse — From date of treatment until the date of when a failure of CIR occurs, whichever comes first, assessed up to 72 months.
Failures of CIR only include relapse and no CR after Induction 2. Other failures including death in resission (before repalse), second malignancy, and off-therapy due to abandonment or attending physician's decision are considered competing risk.
Trial sites (13)
| Facility | City | Region | Status |
|---|
| First Affiliated Hospital Of University of Science and Technology of China |
Hefei |
Anhui |
Not Yet Recruiting |
| The Second Hospital of Anhui Medical University |
Hefei |
Anhui |
Not Yet Recruiting |
| Guangzhou Women and Children Medical Center |
Guangzhou |
Guangdong |
Not Yet Recruiting |
| The First Affiliated Hospital of Guangxi Medical University |
Nanning |
Guangxi |
Not Yet Recruiting |
| Kaifeng Children's Hospital |
Kaifeng |
Henan |
Not Yet Recruiting |
| The First Affiliated Hospital of Zhengzhou University |
Zhengzhou |
Henan |
Not Yet Recruiting |
| Third Xiangya Hospital of Central South University |
Changsha |
Hunan |
Not Yet Recruiting |
| XiangYa Hospital Central South University |
Changsha |
Hunan |
Not Yet Recruiting |
| Children's Hospital of Soochow University |
Suzhou |
Jiangsu |
Recruiting |
| Xuzhou Children's Hospital |
Xuzhou |
Jiangsu |
Not Yet Recruiting |
| Qilu Hospital of Shandong University |
Jinan |
Shandong |
Not Yet Recruiting |
| Children's Hospital Of Fudan University |
Shanghai |
Shanghai Municipality |
Not Yet Recruiting |
| Beijing Institute of Genomics, Chinese Academy of Sciences |
Beijing |
China |
Not Yet Recruiting |
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