QPiAML 2020 study

For the quizartinib study, patients are eligible if they fulfill the inclusion criteria below, initial work-up as described below is done before start of chemotherapy or quizartinib (depending on item), and none of the exclusion criteria applies. However, they can actually enroll in the quizartinib study until day 12 from start of induction course 1, knowing that status of FLT3 and NPM1 must be known before they can be enrolled on this study.
Initial work-up:
• Complete initial work-up within 14 days prior to start of quizartinib, including bone-marrow aspiration, assessment of organ function including cardiac function (ultrasound and ECG). A (diagnostic and therapeutic) lumbar puncture with intrathecal therapy is normally done on day 6 of treatment according to this protocol, but if done earlier will not be considered a protocol violation.
General conditions:
• newly diagnosed, de novo AML with FLT3-ITD and wild-type NPM1
• ≥1 month and ≤ 18 years old at initial diagnosis
• Life expectancy > 6 weeks
• Calculated creatinine clearance ≥ 50 ml/min/1.73m2 as calculated by the Schwartz formula for estimated glomerular filtration rate (GFR) where GFR (ml/min/1.73 m2) = k*Height (cm)/serum creatinine (mg/dl). k is a proportionality constant which varies with age and is a function of urinary creatinine excretion per unit of body size; 0.45 up to 12 months of age; 0.55 children and adolescent girls; and 0.70 adolescent boys.
• Liver function:
Serum bilirubin ≤5 × upper limit of normal (ULN)
Aspartate transaminase (AST)/alanine transaminase (ALT) ≤10×ULN
Other:
• Able to comply with scheduled follow-up and with management of toxicity
• For female patients with childbearing potential, a test for pregnancy is to be done before start of quizartinib, and to be confirmed as negative every 3 months
• Male and female patients must use an highly effective contraceptive method during the study and for a minimum of 6 months after study treatment, as per Clinical Trial Facilitation Group (CTFG) recommendations
• Written informed consent/assent from patients and/or from parents or legal guardians for minor patients, according to local law and regulations

General conditions:
• Secondary AML
• Isolated extramedullary disease
• Acute promyelocytic leukemia (APL)
• Myeloid leukemia of Down Syndrome (ML-DS)
• Other serious illnesses or medical conditions, that will likely make it impossible to complete treatment according to protocol
• Evidence of cardiac dysfunction (shortening fraction below 28% and/or QTc >500 ms)
• Pregnant or lactating patients
Concomitant treatments:
Concomitant administration of any other experimental drug under investigation, or concurrent treatment with any other anti-cancer therapy other than specified in the protocol is not allowed.
G-CSF will not be used for priming and no routine G-CSF support is allowed in between courses, except for life-threatening infections.
Live vaccines within 30 days prior to study start, during the study, and for three months after last dose of chemotherapy or allo-SCT, whichever is latest, is not allowed.