AAML1831: A Phase 3 Randomized Trial for Patients with de novo AML Comparing Standard Therapy Including Gemtuzumab Ozogamicin (GO) to CPX-351 with GO, and the Addition of the FLT3 Inhibitor Gilteritinib for Patients with FLT3 Mutations
What is the goal of the study?
AAML1831 is a randomized Phase 3 trial that will compare efficacy of CPX-351 during Induction 1 and Induction 2 versus standard chemotherapy for children with de novo, non FLT3-mutant AML. This trial incorporates important lessons learned from prior COG Phase 3 studies. As such, gemtuzumab ozogamicin (GO) will be a standard element of each treatment arm. AAML1831 will corporate an updated risk stratification algorithm based on central cytogenetic review and next generation sequencing analysis performed on previous COG Phase 3 studies that provided greater insight into the subset of patients that should be considered high risk. For the primary randomization, cytogenetics, molecular diagnostics, transcriptome sequencing, and end induction multidimensional flow cytometry will be used to risk stratify patients into high risk (HR) and low risk (LR) groups. LR patients will receive 5 blocks of chemotherapy, with exception of favorable cytogenetic/molecular LR patients who are MRD negative at end of Induction 1. The latter patients will receive 4 courses of chemotherapy and reduced cumulative anthracycline, given recent evidence to suggest they have sustained excellent outcomes even with 4 cycles of treatment on AAML1031.2 HR patients will proceed to hematopoietic stem cell transplant (HSCT). Patients with FLT3 mutated AML will have been randomized to CPX-351 and GO vs. standard chemotherapy with GO by the time the FLT3 abnormality is confirmed. Regardless of their primary randomization, patients harboring FLT3 mutations (Including FLT3/ITD with allelic ratio > 0.1 and/or linically relevant non-ITD FLT3 activating mutations) will be eligible for enrollment on one of two treatment arms where they will receive the tyrosine kinase inhibitor (TKI) gilteritinib. Primary Aim To compare event-free survival (EFS) in children with de novo AML without FLT3 mutations who are randomly assigned to standard induction therapy on Arm A (DA-GO) with daunorubicin, cytarabine (DA) and gemtuzumab ozogamicin (GO) versus Arm B with CPX-351 and GO. See protocol Section 1.0 for secondary aims.
Who can participate in the study?
Please contact the study team listed below to learn more.