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Acute Myeloid Leukemia in ChildrenPhase 2CHIP-AML22/QNCT06262438

CHIP-AML22/Quizartinib: Quizartinib + Chemotherapy in Newly Diagnosed Pediatric FLT3-ITD+ and NPM1wt AML Patients

A Phase 2 study testing Quizartinib, Etoposide and Dexrazoxane in people with Acute Myeloid Leukemia in Children, run by Princess Maxima Center for Pediatric Oncology at 1 site in Netherlands.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The CHIP-AML22 Master protocol has the overall aim of increasing the cure rate in newly diagnosed pediatric de novo AML patients, while avoiding unnecessary toxicity. The linked Quizartinib trial (CHIP-AML22/Quizartinib) is a phase II, single arm, open label, study on the safety, efficacy, pharmacokinetics and… Read more about this study

Who is it for?
Ages 1 month to 18 years
Conditions the study is for
Acute Myeloid Leukemia in Children
What is being tested?
Quizartinib, Etoposide and Dexrazoxane
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
1 siteNetherlands
Study dates
6 Feb 2024to Jun 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 month to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
  • 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).
  • Age:
  • Patients must be from 1 month to ≤ 18 years old at initial diagnosis
Show all 40Show fewer
  • 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.
  • 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)
  • Life expectancy: > 6 weeks
  • Pregnancy test:
  • Serum/urine pregnancy test (for all girls ≥ age of menarche) negative within 2 weeks prior to enrollment on the quizartinib linked-trial.
  • Taking quizartinib:
  • Patients must be able to reliably swallow or administer quizartinib by NG tube.
  • 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:
  • Patients with only extramedullary disease
  • 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.
  • 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.
  • 2) Additional exclusion criteria during safety run-in:
  • Patients with CNS3 disease
  • 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)

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Renske Benedictus contact

+31 88 972 72 72

CHIP-AML22@prinsesmaximacentrum.nl

Netherlands1 site, 1 recruiting

  • Princess Máxima Center for pediatric oncology

    Utrecht, Utrecht, 3584 CS

    Gertjan Kaspers, Prof. Dr.

    Bianca Goemans, MD, PhD

    Recruiting

Other trials in Netherlands

About this study

Official title: 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

The CHIP-AML22 Master protocol has the overall aim of increasing the cure rate in newly diagnosed pediatric de novo AML patients, while avoiding unnecessary toxicity. The linked Quizartinib trial (CHIP-AML22/Quizartinib) is 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 AML patients with a FLT3-ITD mutation and NPM1 wild-type.

Read the detailed description

The CHIP-AML22/Quizartinib study is a single-arm, multinational, multicenter, open-label phase II study, with a safety run-in, aiming to assess the safety, efficacy, pharmacokinetics and pharmacodynamics of quizartinib, a FLT3-inhibitor, as IMP added to standard of care chemotherapy in newly diagnosed FLT3-ITD positive and NPM1 wild-type AML pediatric patients.

This study is a linked trial to the CHIP-AML22/Master protocol. Patients will start in the CHIP-AML22/Master study and if they are FLT3-ITD positive and NPM1 wild-type, can be enrolled in the CHIP-AML22/Quizartinib study.

Being tested
Quizartinib, Etoposide, Dexrazoxane, Mitoxantrone, Cytarabine
Keywords
FLT3-ITD+ NPM1wt AML

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • QuizartinibDrug

    Also called AC220, Quizartinib dihydrochoride, Vanflyta

    Quizartinib is a novel oral Class III receptor tyrosine kinase (RTK) inhibitor exhibiting highly potent and selective but reversible inhibition of FMS-like tyrosine kinase FLT3. The dose will be adjusted for the patient's body weight (BW) as measured at the start of each course. Quizartinib will be administered orally once daily and is taken for 14 consecutive days during induction and consolidation courses.

    Induction course 1: Start on day 13; Induction course 2: Start on day 9; Consolidation course 1: Start on day 6; Consolidation courses 2 and 3 (only if no allo-SCT is done): Start on day 6.

    Continuation courses 1-6: patients will receive quizartinib for six 28-day courses. For the first 15 days of course 1 a starting dose will be applicable. On course 1 Day 16, the dose will be increased if the average QTc of the triplicate Electrocardiograms is ≤450 msec on course 1 Day 15. Once the dose is increased, the patient may continue on this dose as long as dose reduction is not needed.

  • EtoposideDrug

    Induction course 1: 150 mg/m2 once daily by Intravenous (IV) infusion over 2 hours (+/- 30 mins) on days 1-5 inclusive (total 5 doses).

    Induction course 2: 150 mg/m2 once daily by IV infusion over 2 hours (+/- 30 mins) on days 6-8 inclusive (total 3 doses).

    Consolidation course 2 (only if no allo-SCT is done): 100 mg/m2 once daily by IV infusion over 1 hour (+/- 15 mins) on days 1-5 inclusive (total 5 doses).

  • DexrazoxaneDrug

    Induction course 1: 250 mg/m2 once daily by 15 mins IV infusion shortly before Mitoxantrone on day 6-10 inclusive (total 5 days), per investigator discretion and per institutional guidelines and availability.

    Induction course 2: 600 mg/m2 once daily by 15 mins IV infusion shortly before daunorubicin on day 2,4,6 inclusive (total 3 does), per investigator discretion and per institutional guidelines and availability.

    Consolidation course 1: 500 mg/m2 once daily by 15 mins IV infusion shortly before Mitoxantrone on 3-5 inclusive (total 3 does), per investigator discretion and per institutional guidelines and availability.

  • MitoxantroneDrug

    Induction course 1: 5 mg/m2 once daily by IV infusion over 1 hour (+/- 15 mins) on days 6-10 inclusive (total 5 doses). Please note that mitoxantrone and cytarabine should not be given concomitantly. Mitoxantrone should be completed before cytarabine is given.

    Consolidation course 1: 10 mg/m2 once daily by IV infusion over 1 hour (+/- 15 mins) on days 3-5 inclusive (total 3 doses).

  • CytarabineDrug

    Induction course 1: 200 mg/m2 once daily by IV infusion over 12 hours (+/- 1 hour) on days 6-12 inclusive (total 7 doses), following mitoxantrone. Induction course 2: 100 mg/m2 once daily by continuous IV infusion on days 1-2 inclusive. And 100 mg/m2 twice daily as a 30min (+/- 10 mins) IV infusion every 12 hours on days 3-8 inclusive (total 12 doses). Consolidation course 1: 1000 mg/m2 twice daily by IV infusion over 2 hours (+/- 30 min) every 12 hours on days 1-3 inclusive (total 6 doses).

    Consolidation course 2 (only if no allo-SCT is done): 3000 mg/m2 twice daily by IV infusion over 2 hours (+/- 30 mins) every 12 hours on days 1-3 inclusive (total 6 doses).

    Consolidation course 3 (only if no allo-SCT is done): 2000 mg/m2 once daily by IV infusion over 3 hours (+/- 1 hour) starting 4 hours after fludarabine on days 1-5 inclusive (total 5 doses), following fludarabine.

  • MethotrexateDrug

    Induction course 1: Methotrexate (MTX) Intrathecal therapy (IT) prophylaxis is age-adjusted. If MTX is given at diagnosis omit IT therapy on day 6 unless in case of CNS involvement (CNS3). For children with initial CNS involvement (CNS3) MTX IT is replaced with triple IT and given more frequently. For children with CNS2, CSF must be investigated on day 22; if leukemic cells persist, treat as CNS3.

    Induction course 2, Day 1: MTX (IT) prophylaxis is age-adjusted. For children with initial CNS involvement (CNS3) MTX IT is replaced with triple IT and given more frequently.

    Consolidation course 1, Day 1: MTX (IT) prophylaxis is age-adjusted. For children with initial CNS involvement (CNS3) MTX IT is replaced with triple IT and given more frequently.

    Consolidation course 2 and 3, Day 1 (only if no allo-SCT is done): MTX (IT) prophylaxis is age-adjusted. For children with initial CNS involvement (CNS3) MTX IT is replaced with triple IT and given more frequently.

  • DaunorubicinDrug

    Induction course 2: 60 mg/m2 once daily by IV infusion over 1 hour (+/- 15 mins) on days 2,4,6 inclusive (total 3 doses).

  • FludarabineDrug

    Consolidation course 3 (only if no allo-SCT is done): 30 mg/m2 once daily by IV infusion over 30 mins (+/- 10 mins) on days 1-5 inclusive (total 5 doses).

  • allo-SCTOther

    The SCT procedure is left to the discretion of the investigator and not part of this protocol.

Study groups in NCT06262438
Study groupRoleWhat they receive
QuizartinibExperimentalQuizartinib will be administered for 14 days following the completion of standard of care chemotherapy for up to 3-5 cycles of induction and consolidation. After high dose chemotherapy or allo-Stem Cell Transplantation (allo-SCT), patients will receive continuation treatment with quizartinib for six 28-day courses
Receives: Drug: Quizartinib; Drug: Etoposide; Drug: Dexrazoxane; Drug: Mitoxantrone; Drug: Cytarabine; Drug: Methotrexate; Drug: Daunorubicin; Drug: Fludarabine; Other: allo-SCT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Primary objective (efficacy)

    The percentage of patients with (Minimal Residual Disease) MRD levels <0.1% (MRD negativity) after up to 2 courses of induction chemotherapy plus quizartinib, as measured in the bone marrow using multiparameter flow cytometry (MFCM) before start of consolidation therapy, in the evaluable population for response.

    • Patients to be evaluated at baseline, end of cycle 1, and end of cycle 2

    Measured: 2 induction courses (maximum of 56+/-2 days per course)

  2. Primary objective (safety)

    Incidence of Dose-Limiting Toxicities (DLTs) assessed during Induction course 1 and 2 (until day 56 of each course) for the DLTs evaluable patients.

    Measured: 2 induction courses (maximum of 56+/-2 days per course)

Secondary outcomes (15)

  1. Secondary objectives (efficacy_1)

    Morphological overall response rate (ORR)

    Measured: 2 induction courses (maximum of 56+/-2 days per course)

  2. Secondary objectives (efficacy_2)

    MRD by multiparameter flow cytometry (MFCM)

    Measured: Multiple time points, last time point after continuation treatment (1.5 years)

  3. Secondary objectives (efficacy_3)

    Event free survival (EFS)

    Measured: 3 years

  4. Secondary objectives (efficacy_4)

    Overall survival (OS)

    Measured: 3 years

  5. Secondary objectives (efficacy_5)

    Disease free survival (DFS)

    Measured: 3 years

  6. Secondary objectives (efficacy_6)

    Duration of response

    Measured: 3 years

  7. Secondary objectives (efficacy_7)

    Cumulative incidence of relapse (CIR)

    Measured: 3 years

  8. Secondary objectives (efficacy_8)

    Number and percentage of patients actually being treated with hematopoietic stem cell transplantation (HSCT)

    Measured: 1 year

  9. Secondary objectives (efficacy_9)

    Number of patients starting and completing continuation treatment post-HSCT.

    Measured: 1.5 years

  10. Secondary objectives (safety) - Adverse Events, Laboratory Abnormalities and cumulative incidence of non-relapse mortality

    Safety and tolerability of combining quizartinib with conventional treatment and quizartinib given as single-agent after HSCT.

    • Adverse events (AEs), as characterized by type, frequency, severity (as graded using CTCAE, v5.0).
    • Laboratory abnormalities (including time to recovery of ANC and PLT), electrocardiograms and changes in vital signs as characterized by type, frequency, severity and timing will be tabulated, and reported as AEs when considered clinically significant by the investigator.
    • The cumulative incidence of non-relapse mortality, defined as the cumulative probability of non-relapse mortality, with time calculated between start of study treatment and death due to other causes than relapsed or refractory leukemia, accounting for competing events.

    Measured: 1.5 years

  11. Pharmacokinetics (PK_1)

    Population PK analysis to estimate AUC (tau) for quizartinib and AC886

    Measured: 1.5 years

  12. Pharmacokinetics (PK_2)

    Population PK analysis to estimate Cmax for quizartinib and AC886

    Measured: 1.5 years

  13. Pharmacokinetics (PK_3)

    Population PK analysis to estimate clearance (CL/F) for quizartinib.

    Measured: 1.5 years

  14. Pharmacokinetics (PK_4)

    Population PK analysis to estimate volume of distribution (Vss/F) for quizartinib.

    Measured: 1.5 years

  15. Palatability of quizartinib formulations

    Patients and/or parents or legal guardians will answer using a Hedonic scale for the taste and ability to swallow the medicine.

    Measured: 1.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Feb 2024
  2. Study start6 Feb 2024
  3. Primary completionJun 2028 (estimated)
  4. Study completionJun 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Given the rarity of pediatric subjects with newly diagnosed Acute Myeloid Leukemia (AML) with FLT3-ITD mutations and the slow enrollment in historical studies, it is not feasible to enroll a sufficient number of subjects for an adequately powered randomized study. Therefore, a standard oncology Phase 2 response-rate design has been chosen. One of the exploratory objectives planned is to compare the outcome of patients treated in this study to the outcome of patients treated in the NOPHO-DBH AML-2012 study as historical control.
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06262438
Sponsor's protocol ID
MH22CAQ
Other IDs
2022-002886-14, 2023-505000-27, 2023
Acronym
CHIP-AML22/Q
Status last verified
Jul 2025
First submitted
26 Jan 2024
Last updated
5 Aug 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All individual participant data will be used to generate a publication

Publications

  • Kaspers GJL, van Hamel M, Abrahamsson J, Arad-Cohen N, Benedictus R, Scheidegger N, Castillo L, Ka Leung Cheuk D, Costa V, Duong Y, Fernandez Navarro JM, Fogelstrand L, Goemans BF, Ishimaru S, Jonsson OG, Juul-Dam KL, Karu M, Koedijk JB, Kovalova Z, De Moerloose B, Munthe-Kaas MC, Palmu S, Pasauliene R, Tierens A, van Tinteren H, Turkiewicz D, Valerio DG, Wijnen N, Zwaan CM, Pronk CJ. CHIP-AML22: a complex clinical trial in de novo pediatric AML patients, including a gemtuzumab ozogamicin randomization and targeted therapy with quizartinib in eligible subgroups, within the NOPHO-DB-SHIP consortium. Trials. 2026 Jun 20. doi: 10.1186/s13063-026-09855-5. Online ahead of print.

    PubMed 42321916

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Quizartinib, Etoposide and Dexrazoxane in people with Acute Myeloid Leukemia in Children, run by Princess Maxima Center for Pediatric Oncology at 1 site in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 40 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Renske Benedictus (+31 88 972 72 72, CHIP-AML22@prinsesmaximacentrum.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Primary objective (efficacy) (time frame: 2 induction courses (maximum of 56+/-2 days per course)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06262438, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2025.

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