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.
Advances in risk stratification and therapy, have improved the event-free survival (EFS) and overall survival (OS) for pediatric acute myeloid leukemia (AML) with current treatment strategies. Investigators previously conducted a multicenter, randomized controlled trial (AML18) to compare the efficacy and safety of low-dose chemotherapy versus standard-dose chemotherapy. The results showed that low-dose chemotherapy was non-inferior to standard-dose chemotherapy in terms of efficacy and had fewer adverse events. However, different subtypes exhibited varying treatment responses to both chemotherapy regimens. The MRD (Measurable Residual Disease) after induction therapy in both groups had an impact on prognosis. According to the backbone of the 2018 protocol, investigators decide whether to use low-dose or standard-dose for the first induction according to the patient's fusion gene, and the second induction and subsequent treatment are adjusted according to the treatment response. Patients with the following 5 fusion genes RUNX1: RUNX1T1, CBFβ: MYH11, KMT2A: MLLT3 (AF9), KMT2A: MLLT10 (AF10), KMT2A: MLLT4 (AF6) fusion or KIT mutation will be assigned to the standard dose remission induction regimen (HHT + Ara-C + VP16), others will be assigned to the standard dose regimen (Mitoxantrone/Idarubicin + Ara-C + G-CSF). At the same time, investigators will add targeted drugs such as venetoclax, avaptitinib, and gilteritinib/sorafenib to the chemotherapy regimen and assess their safety and efficacy. Post-induction consolidation consisted of 3 to 4 cycles of standard-dose chemotherapy according to risk classification. Patients classified as high-risk are candidates for allogeneic bone marrow transplantation after 1 or 2 courses of consolidation.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
500
3mg/m2/day for weighing \>10kg, 0.1mg/kg/day for weighing ≤10kg, d1-7, ivgtt, qd, more than 6 hours
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;
100mg/m2/d for weighing \>10kg, 3.3mg/kg/d for weighing ≤ 10kg, d1-5, ivgtt, qd, more than 4 hours
100mg/m2/d for weighing \>10kg, 3.33mg/kg/d for weighing ≤10kg, d12-25, po, qd
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.
5ug/kg/d, d1-10, s.c., qd, at 1pm
3mg/m2/day for weighing \>10kg, 0.1mg/kg/day for weighing ≤ 10kg, d1-7, ivgtt, qd, more than 6 hours.
100mg/m2/day for weighing \>10kg, 3.3mg/kg/day for weighing ≤10kg, from identification, po, qd
20mg/m2/day for weighing \>10kg, 0.7mg/kg/day for weighing ≤ 10kg, from identification, po, qd
50mg/m2/day for weighing bodyweight \>10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd
First Affiliated Hospital Of University of Science and Technology of China
Hefei, Anhui, China
NOT_YET_RECRUITINGThe Second Hospital of Anhui Medical University
Hefei, Anhui, China
NOT_YET_RECRUITINGGuangzhou Women and Children Medical Center
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGThe First Affiliated Hospital of Guangxi Medical University
Nanning, Guangxi, China
NOT_YET_RECRUITINGKaifeng Children's Hospital
Kaifeng, Henan, China
NOT_YET_RECRUITINGThe First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
NOT_YET_RECRUITINGThird Xiangya Hospital of Central South University
Changsha, Hunan, China
NOT_YET_RECRUITINGXiangYa Hospital Central South University
Changsha, Hunan, China
NOT_YET_RECRUITINGChildren's Hospital of Soochow University
Suzhou, Jiangsu, China
RECRUITINGXuzhou Children's Hospital
Xuzhou, Jiangsu, China
NOT_YET_RECRUITING...and 3 more locations
Rate of CR/CRi with negative MRD
CR/CRi with negative MRD was defined as less than 5% blasts in bone marrow and MRD \<0.1%.
Time frame: Day 26 (HAE group) and Day 32 (MAG+Ven group) for remission induction 1 and 2 are the necessary time points for response evaluation.
Event-free survival
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.
Time frame: 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.
Cumulative incidence of relapse
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.
Time frame: From date of treatment until the date of when a failure of CIR occurs, whichever comes first, assessed up to 72 months.
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