The researchers are doing this study to see if the combination of gilteritinib with ivosidenib or enasidenib is a safe and effective treatment for people with relapsed/refractory AML with FLT3/IDH1 or FLT3/IDH2 gene mutations. The researchers will also look for the highest dose of the combination of gilteritinib with ivosidenib or enasidenib that causes few or mild side effects. When the highest safe dose is found, they will test that dose in new groups of participants.
Adult patient is ≥18 years of age at the time of signing the informed consent form (ICF)
Patient is willing and able to adhere to the study visit schedule and other protocol requirements.
For patients who received intensive induction chemotherapy they must have persistent AML (defined as overt disease with over 5% myeloblasts) after at least one cycle of intensive induction OR
For patients treated with low intensity therapy, the patient must be refractory to treatment with a single agent hypomethylating agent (HMA) or low dose cytarabine (LDAC) (at least two cycles) or an HMA/LDAC in combination with venetoclax (at least one cycle) or another standard of care therapy (e.g. gemtuzumab ozogamicin, glasdegib/LDAC).
Patient has a diagnosis of acute promyelocytic leukemia (APL).
Patient on any other investigational anti-cancer agents.
Patient has active uncontrolled systemic fungal, bacterial, or viral infection.
Patient has presence of any other condition that may increase the risk associated with study participation, and in the opinion of the investigator, would make the patient inappropriate for entry into the study.
Parallel
Gilteritinib
DrugDose level (-1) 80mg, (1) 120mg, (2) 120mg
Ivosidenib
DrugDose level (-1) 250mg, (1) 250mg, (2) 500mg
Enasidenib
DrugDose level (-1) 50mg, (1) 50mg, (2) 100mg
Determine the maximum tolerated dose (MTD)
These are derived based on Dose Limiting Toxicities (DLT) according to BOIN dose escalation methodology.
Adverse events /toxicities
will be graded using CTCAE 5.0 and described by frequency, duration and severity of treatment-emergent, treatment-related, and serious adverse events.
Clinical response
The ORR will be estimated by sample proportion with 95% confidence intervals calculated based on exact binomial distribution.
Click on the lead sponsor to view all of their trials.
Memorial Sloan Kettering Cancer Center
Lead sponsor
Astellas Pharma US, Inc.
Collaborator
