This phase III trial compares standard chemotherapy to therapy with liposome-encapsulated daunorubicin-cytarabine (CPX-351) and/or gilteritinib for patients with newly diagnosed acute myeloid leukemia with or without FLT3 mutations. Drugs used in chemotherapy, such as daunorubicin, cytarabine, and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. CPX-351 is made up of daunorubicin and cytarabine and is made in a way that makes the drugs stay in the bone marrow longer and could be less likely to cause heart problems than traditional anthracycline drugs, a common class of chemotherapy drug. Some acute myeloid leukemia patients have an abnormality in the structure of a gene called FLT3. Genes are pieces of DNA (molecules that carry instructions for development, functioning, growth and reproduction) inside each cell that tell the cell what to do and when to grow and divide. FLT3 plays an important role in the normal making of blood cells. This gene can have permanent changes that cause it to function abnormally by making cancer cells grow. Gilteritinib may block the abnormal function of the FLT3 gene that makes cancer cells grow. The overall goals of this study are, 1) to compare the effects, good and/or bad, of CPX-351 with daunorubicin and cytarabine on people with newly diagnosed AML to find out which is better, 2) to study the effects, good and/or bad, of adding gilteritinib to AML therapy for patients with high amounts of FLT3/ITD or other FLT3 mutations and 3) to study changes in heart function during and after treatment for AML. Giving CPX-351 and/or gilteritinib with standard chemotherapy may work better in treating patients with acute myeloid leukemia compared to standard chemotherapy alone.
All patients must be enrolled on APEC14B1 and consented to Eligibility Screening (Part A) prior to enrollment and treatment on AAML1831. Bone marrow and/or blood must have been submitted to the BPC via APEC14B1 for testing of FLT3 markers. Patients without samples submitted for FLT3 testing are not eligible
Patients must be at least 6 months of age and less than 22 years of age at the time of study enrollment
Patient must be newly diagnosed with de novo AML according to the 2016 World Health Organization (WHO) classification with or without extramedullary disease
>= 20% bone marrow blasts (obtained within 14 days prior to enrollment)
Fanconi anemia
Shwachman Diamond syndrome
Patients with constitutional trisomy 21 or with constitutional mosaicism of trisomy 21
Telomere disorders
Parallel
Allogeneic Hematopoietic Stem Cell Transplantation
Procedure/SurgeryUndergo allogeneic HSCT
Asparaginase Erwinia chrysanthemi
DrugGiven IM or IV
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Bone Marrow Aspiration
Procedure/SurgeryUndergo BM aspiration
Bone Marrow Biopsy
Procedure/SurgeryBM biopsy
Computed Tomography
Procedure/SurgeryUndergo CT
Cytarabine
DrugGiven IV or IT
Daunorubicin Hydrochloride
DrugGiven IV
Dexrazoxane Hydrochloride
DrugGiven IV
Etoposide
DrugGiven IV
Fludeoxyglucose F-18
Other interventionUndergo FDG-PET
Gemtuzumab Ozogamicin
DrugGiven IV
Gilteritinib Fumarate
DrugGiven PO/NG/G-tube
Liposome-encapsulated Daunorubicin-Cytarabine
DrugGiven IV
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Methotrexate
DrugGiven IT
Mitoxantrone Hydrochloride
DrugGiven IV
Positron Emission Tomography
Procedure/SurgeryUndergo FDG-PET
Questionnaire Administration
Other interventionAncillary studies
Therapeutic Hydrocortisone
DrugGiven IT
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Treatment groupsSee each treatment group below.
Event-free survival (EFS)
The Kaplan-Meier method will be used to estimate 3-year EFS, defined as the time from study entry until induction failure, relapse, or death.
Overall survival (OS)
The Kaplan-Meier method will be used to estimate 3-year OS, defined as the time from study entry until death.
Proportion of patients positive for minimal residual disease (MRD+)
The proportion of patients MRD+ at end of induction 1 (EOI1) will be estimated as the number of patients MRD+ divided by the number of patients with evaluable EOI1 MRD results along with a corresponding 95% confidence interval determined using a binomial exact method.
Proportion of patients who died during protocol therapy
The proportion of patients who died during protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method.
Incidence of adverse events
The proportion of patients experiencing at least one grade 3 or higher non-hematologic toxicity and infection while on protocol therapy will be estimated along with the corresponding 95% confidence interval determined using a binomial exact method. Toxicity will be assessed by Common Terminology Criteria for Adverse Events version 5.0.
Course duration
Median and range of the length of course duration will be determined.
Length of hospitalization
Median and range of the length of hospitalization time during protocol therapy will be determined.
Time to count recovery
Cumulative incidence estimates that account for competing events will be used to estimate time to count recovery in days where deaths are competing events.
EFS by sex
National Institutes of Health (NIH)-required analysis. The Kaplan-Meier method will be used to estimate 3-year EFS by sex. EFS is defined as the time from study entry until induction failure, relapse, or death.
Click on the lead sponsor to view all of their trials.
Children's Oncology Group
Lead sponsor
National Cancer Institute (NCI)
Collaborator
