AML, Childhood, Relapse/Recurrence, Refractory AML, Core Binding Factor Acute Myeloid Leukemia, C-KIT Mutation
Conditions
Keywords
Avapritinib, KIT, CBF AML, Childhood, Relapsed/Refractory
Brief summary
The purpose of this study is to evaluate the efficacy and safety of avapritinib in relapsed or refractory pediatric core binding factor acute myeloid leukemia with KIT mutation.
Detailed description
This is a multicenter, single-arm, prospective, and intervention trial. About 30% of core binding factor acute myeloid leukemia (CBF-AML) patients still relapse under current treatment. Some studies have found that KIT mutations, especially the D816V mutation, may predict relapse and decrease overall survival (OS) in CBF-AML. Avapritinib has been approved for the treatment of gastrointestinal stromal tumors with KIT or PDGFRA mutations. Avapritinib was also effective for the treatment of minimal residual disease in acute myeloid leukemia with t (8;21) and KIT mutation failing to immunotherapy after allogeneic hematopoietic stem cell transplantation in a single-center, retrospective report. 11 centers from China carry out the AVACBFKIT regimen including Avapritinib, hypomethylating agents and low dose chemotherapy for the treatment of relapsed or refractory pediatric CBF-AML with KIT mutation. The main focus of this study is to evaluate the efficacy and safety of avapritinib in the regimen.
Interventions
DRUGAvapritinib
50mg/m2/day for weighing bodyweight \>10kg, 1.65mg/kg/day for weighing ≤ 10kg, po, qd, d1-28.
75mg/m2/d for weighing \>10kg, 2.5mg/kg/d for weighing ≤ 10kg, d1-7, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously.
20mg/m2/d for weighing \>10kg, 0.67mg/kg/d for weighing ≤ 10kg, d1-5, ivgtt, qd, more than 3 hours. Azacitidine and decitabine cannot be used simultaneously.
5mg/m2/day for weighing \>10kg, 0.17mg/kg/day for weighing ≤ 10kg, d 6, 8, 10 (d 8, 10, 12 for azacitidine) ivgtt, qod, more than 1 hour at 10 am.
DRUGCytarabine
10mg/m2/day for weighing \>10kg, 0.33mg/kg/day for weighing ≤ 10kg, d6-15 （d8-17 for azacitidine ）, s.c., q12h.
DRUGGranulocyte Colony-Stimulating Factor
300ug/day for weighing \>10kg, 10ug/kg/day for weighing ≤10kg, d0-5, s.c., qd.
Sponsors
Children's Hospital of Soochow University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Gender unlimited; 2. Under 18 years; 3. Diagnosis of acute myeloid leukemia (according to the 2022 WHO classification). 4. Presence of t(8;21)/RUNX1::RUNX1T1 or inv(16)/t(16;16)/CBFβ::MYH11; 5. KIT mutation; 6. Refractory AML: AML patients who do not achieve CR or CRi after induction therapy; 7. Relapsed AML: patients who achieved remission after consolidation therapy or transplantation, FISH confirmed that the fusion gene turned positive, or extramedullary leukemia infiltration; 8. No active infections; 9. Liver function: Tbil ≤2×ULN, ALT/AST ≤3×ULN, creatinine clearance ≥50ml/min; 10. ECOG score \<2; 11. Expected survival time \>12 weeks; 12. Participants must have the ability to understand and be willing to participate in this study and must sign an informed consent form.
Exclusion criteria
1. Have received prior treatment with avapritinib; 2. Receiving other targeted therapies for AML at the same time, such as dasatinib, sorafenib, gilteritinib, venetoclax, etc; 3. Presence of active uncontrolled infection (including bacterial, fungal, or viral infection); 4. Present of significant underlying organ diseases: such as myocardial infarction, chronic heart failure, decompensated liver or kidney dysfunction； 5. With other malignancies requiring treatment； 6. Already enrolled in another interventional clinical study； 7. The researchers determined that the individual is not suitable to participate in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite remission rate (CRc) | The evaluation time point is day28-day35 from the start of regimen. | Composite remission rate (CRc), including the sum of the number of patients with complete remission (CR), complete remission with partial hematologic recovery (CRh), complete remission with incomplete blood count recovery (CRi), and morphologically leukemia-free (MLFS) as a percentage of the total number of patients who participated in the efficacy analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival | From date of enrollment until the date of the occurrence of death or last follow-up, assessed up to 60 months. | Overall survival (OS) was defined as the date from enrollment to the date of death or last follow-up for surviving patients. |
| Progression-free survival | From date of enrollment until the date of disease progression, confirmed relapse, or death, whichever occurred first, assessed up to 60 months. | Progression-free survival (PFS) was defined as the date from enrollment to the date of disease progression, confirmed relapse, or death, whichever occurred first. |
Countries
China
Contacts
Primary ContactShaoyan Hu, MD, PhD
Backup ContactLi Gao, MD
Outcome results
None listed