Acute Myeloid Leukemia (AML) blood cancer
Conditions
Interventions
Induction chemotherapy will consist of MEC (mitoxantrone, etoposide,
cytarabine) plus quizartinib as first induction course, followed by ADE
(cytarabine, daunorubicin, etoposide) plus quizartinib as
Sponsors
Prinses Máxima Centrum voor Kinderoncologie
Eligibility
Age
No minimum to 64 Years
Inclusion criteria
Inclusion criteria: 1) Enrollment on CHIP-AML22/Master: Patients must be enrolled on the CHIP-AML22/Master prior to enrolment on CHIP-AML/Quizartinib linked-trial, and may have received a diagnostic work-up according to the master protocol. Induction treatment can be started as standard of care. 2) FLT3-ITD+ and wild-type NPM1: Presence of FLT3-ITD+ and NPM1 wild type in bone marrow or peripheral blood provided by the local laboratories, as part of standard of care diagnostics. The results of FLT3-ITD testing must be obtained prior to the first dose of quizartinib (e.g., Induction course 1, Day 10). 3) Age: Patients must be from 1 month to 50% for subjects >16 years of age, and a Lansky performance status score of >50% for subjects = 50 mL/min/1.73 m2 using the Schwartz formula. b. Adequate Liver Function Defined as: • Total or direct (conjugated) bilirubin 6 weeks 7) Pregnancy test: Serum/urine pregnancy test (for all girls >= age of menarche) negative within 2 weeks prior to enrollment on the quizartinib linked-trial. 8) Taking quizartinib: Patients must be able to reliably swallow or administer quizartinib by NG tube. 9) Informed consent: Written informed consent/assent for the quizartinib linked trial from patients and/or from parents or legal guardians for minor patients, according to local law and regulations.
Exclusion criteria
Exclusion criteria: General exclusion criteria a. Patients with only extramedullary disease b. Uncontrolled or significant cardiovascular disease, including i. Diagnosed or suspected congenital long QT syndrome ii. History of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes); any history of arrhythmia will be discussed with sponsor, the national coordinator and C.I. the prior to subject*s entry into the study. iii. QT interval corrected >450 ms: - QTc interval corrected with Fridericia*s formula (QTcF) for subjects >= 6 years of age at the time of enrollment. iv. Left ventricular systolic dysfunction (LVSD), defined as ejection fraction (EF) below 55% during the screening for the CHIP-AML22/Master protocol. v. History of uncontrolled angina pectoris or myocardial infarction within 6 months. vi. History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker). vii. Heart rate
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Objective (efficacy): To assess the clinical benefit of quizartinib as measured by the MRD-negativity rate (defined as | — |
Secondary
| Measure | Time frame |
|---|---|
| Secundary Objectives: - Efficacy To explore the added anti-leukemic effect of quizartinib based on other measures of response, as defined as secondary endpoints, including morphological overall response rate (ORR), MRD by MFCM, event free survival (EFS), overall survival (OS), disease free survival (DFS), duration of response, cumulative incidence of relapse (CIR), number and percentage of patients actually being treated with hematopoietic stem cell transplantation (HSCT), number of patients starting and completing continuation treatment post-HSCT. Endpoints: Other measurements of treatment response: - Proportion of subjects with a complete remission (CR) rate without evidence of MRD after 1 and after 2 induction courses (including CR and remission with incomplete blood count or platelet recovery) - Bone marrow blast counts by morphology and MFCM after induction course 1 and induction course 2 and before allo-SCT; CRc (CR and CRi) and morphologic leukemia-free state (MLFS) rates after induction course 1 and 2; MRD negativity ( | — |
Countries
Netherlands
Outcome results
None listed