Combining Quizartinib with Chemotherapy for Pediatric AML Patients
A Phase II, Single Arm, Open Label, Study on the Safety, Efficacy, Pharmacokinetics & Pharmacodynamics of Quizartinib + Chemotherapy and as Single-agent After High Dose Therapy in Newly Diagnosed Pediatric FLT3-ITD+ and NPM1wt AML Patients
This study is testing if adding a new drug called quizartinib to standard chemotherapy can help children with a specific type of leukemia feel better and have better treatment outcomes.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 60 (estimated) |
| Ages | 1 Month to 18 Years |
| Sex | All |
| Sponsor | Princess Maxima Center for Pediatric Oncology Academic / other |
| Drugs / interventions | Quizartinib, chemotherapy |
| Locations | 1 site (Utrecht, Utrecht) |
| Trial ID | NCT06262438 on ClinicalTrials.gov |
What this trial studies
This study evaluates the safety and efficacy of quizartinib, a FLT3-inhibitor, when combined with standard chemotherapy in newly diagnosed pediatric patients with acute myeloid leukemia (AML) who have a FLT3-ITD mutation and NPM1 wild-type. It is a single-arm, open-label phase II trial that aims to improve cure rates while minimizing toxicity. Patients will first enroll in a master protocol and, if eligible, will receive quizartinib as part of their treatment regimen. The study also assesses the pharmacokinetics and pharmacodynamics of quizartinib in this patient population.
Who should consider this trial
Good fit: Ideal candidates are pediatric patients aged 1 month to 18 years diagnosed with FLT3-ITD positive and NPM1 wild-type acute myeloid leukemia.
Not a fit: Patients without the FLT3-ITD mutation or those with NPM1 mutations may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could significantly improve treatment outcomes for children with a specific type of AML.
How similar studies have performed: Other studies have shown promise in targeting FLT3 mutations in AML, suggesting that this approach could be beneficial.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion criteria:
1. Enrollment on CHIP-AML22/Master:
Patients must be enrolled on the CHIP-AML22/Master prior to enrollment 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 \< 1.5xULN 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:
1. Patients with only extramedullary disease
2. Uncontrolled or significant cardiovascular disease, including -Diagnosed or suspected congenital long QT syndrome
-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.
-QT interval corrected \>450 ms: QTc interval corrected with Fridericia's formula (QTcF) for subjects ≥ 6 years of age at the time of enrollment.
-Left ventricular systolic dysfunction (LVSD), defined as ejection fraction (EF) below 55% during the screening for the CHIP-AML22/Master protocol.
-History of uncontrolled angina pectoris or myocardial infarction within 6 months.
-History of second (Mobitz II) or third degree heart block (subjects with pacemakers are eligible if they have nohistory of fainting or clinically relevant arrhythmias while using the pacemaker).
-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.)
-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).
* History of complete left bundle branch block.
* History of New York Heart Association Class 3 or 4 heart failure.
3. Known history of HIV or active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C)
4. Underlying GI disease that may affect absorption of study drug
5. 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.
6. History of hypersensitivity to any of the study medications or their excipients.
7. 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)
8. Currently participating in other investigational interventional procedures, if it interferes with any endpoints of the quizartinib trial.
2\) Additional exclusion criteria during safety run-in:
1. Patients with CNS3 disease
2. 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)
Where this trial is running
Utrecht, Utrecht
- Princess Máxima Center for pediatric oncology — Utrecht, Utrecht, Netherlands (Recruiting)
Study contacts
- Study coordinator: Renske Benedictus
- Email: CHIP-AML22@prinsesmaximacentrum.nl
- Phone: +31 88 972 72 72
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.