CHIP-AML22/Quizartinib sub-study: study of the safety and efficacy of quizartinib in children and adolescents with FLT3-ITD positive AML with normal NPM1.

Phase 1

Recruiting

Conditions: newly diagnosed pediatric FLT3-ITD positive and NPM1 wild-type AML
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2023-505000-27-01

Lead Sponsor: Prinses Maxima Centrum voor Kinderoncologie B.V.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 41

Inclusion Criteria

Enrollment on CHIP-AML22/Master, FLT3-ITD+ and wild-type NPM1, Age from 1 month to = 18 years old at initial diagnosis, Karnofsky Performance status of >50% for subjects >16 years of age, and a Lansky performance status score of >50% for subjects =16 years of age, Organ function criteria: a. Adequate Renal Function Defined as: • Calculated eGFR = 50 mL/min/1.73 m2 b. Adequate Liver Function Defined as: • Total or direct (conjugated) bilirubin <1.5 × ULN for age (= 5xULN if related to leukemic involvement), AND • Aspartate transaminase (AST) and alanine transaminase (ALT) <5xULN (<10×ULN if related to leukemic involvement),, Life expectancy: > 6 weeks, Pregnancy test negative within 2 weeks prior to enrollment on the quizartinib linked-trial., Patients must be able to reliably swallow or administer quizartinib by NG tube., 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

Patients with only extramedullary disease, 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 <50 beats/minute on ECG during the screening for the CHIPAML22/ Master protocol (In case, adolescents with a normal sinusoidal rhythm and no evidence of other cardiac dysfunction will be discussed with sponsor, the national coordinator and C.I. the prior to subject’s entry into the study.) viii. Uncontrolled hypertension (e.g., systolic blood pressure and /or diastolic blood pressure that is, on repeated measurement, at or above the 95th percentile for sex, age, and height). ix. History of complete left bundle branch block. x. History of New York Heart Association Class 3 or 4 heart failure., Known history of HIV or active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C), Underlying GI disease that may affect absorption of study drug, Use of strong or moderate CYP3A inducers will be prohibited throughout the duration of the study. Strong CYP3A4 inhibitors will be allowed with a concomitant dose reduction of quizartinib with the exception during the safety run-in., History of hypersensitivity to any of the study medications or their excipients., Other serious illnesses or medical conditions, that will likely make it impossible to complete treatment according to protocol (e.g., patients who should not be given any of the study medications based on the SmPC), Currently participating in other investigational interventional procedures, if it interferes with any endpoints of the quizartinib trial, Additional exclusion criteria during safety run-in a. Patients with CNS3 disease b. Using strong CYP3A4 inhibitors (If patient can stop using strong CYP3A4 inhibitors, he/she will be allowed to enroll. In such case, no washout is required for the strong CYP3A4 inhibitor)