CHIP-AML22/Quizartinib: A phase II, single arm, open label, study on the safety, efficacy, pharmacokinetics and pharmacodynamics of quizartinib in combination with chemotherapy and as single-agent after high dose therapy in newly diagnosed pediatric FLT3-ITD positive and NPM1 wild type AML patients. (A linked-trial of the CHIP-AML22/Master protocol by the NOPHO-DB-SHIP consortium)
- Conditions
- Acute Myeloid Leukemia (AML)blood cancer10024324
- Registration Number
- NL-OMON53485
- Lead Sponsor
- Prinses Máxima Centrum voor Kinderoncologie
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 9
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 <= 18 years old at initial diagnosis
4) Performance status
Karnofsky performance status score of >50% for subjects >16 years of age, and a
Lansky performance status score of >50% for subjects <=16 years of age.
5) Organ function criteria:
These criteria must be met based on the results before start of any
chemotherapy (e.g., MEC)
a. Adequate Renal Function Defined as:
• Calculated eGFR >= 50 mL/min/1.73 m2 using the Schwartz formula.
b. Adequate Liver Function Defined as:
• Total or direct (conjugated) bilirubin < 5xULN for age (<= 5xULN if related to
leukemic
involvement), AND
• Aspartate transaminase (AST) and alanine transaminase (ALT) <5xULN (<10×ULN if
related to leukemic involvement)
6) Life expectancy: > 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.
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 <50 beats/minute on ECG during the screening for the
CHIP-AML22/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.
c. Known history of HIV or active clinically relevant liver disease (e.g.,
active hepatitis B or active hepatitis C)
d. Underlying GI disease that may affect absorption of study drug
e. 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.
f. History of hypersensitivity to any of the study medications or their
excipients.
g. 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)
h. Currently participating in other investigational interventional procedures,
if it interferes with any endpoints of the quizartinib trial.
Note: Patients may be enrolled in either SCRIPT-AML or Pro-Teico study (i.e.,
conditioning regimen for allo-SCT or infection prophylaxis) as
a) The endpoints of the quizartinib trials are not influenced
b) These trials are evaluating approved agents
c) The medications being evaluated do not conflict with the mechanism of action
of quizartinib
2) 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)
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method