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RecruitingNCT05994690Updated Aug 5, 2025

CHIP-AML22/Master: An Open Label Complex Clinical Trial in Newly Diagnosed Pediatric de Novo AML Patients

A Phase 3 interventional study of Standard Intervention Rc and Investigational Intervention Rc in Acute Myeloid Leukemia in Children, sponsored by Princess Maxima Center for Pediatric Oncology. Recruiting at 1 site in Netherlands. Open to participants aged 1 Day to 18 Years. Per ClinicalTrials.gov, last updated 2025-08-05.

Sponsored by Princess Maxima Center for Pediatric Oncology · Phase 3, Interventional, and Treatment

From the registry’s dates

  • Started Jul 2023; still recruiting 3 years 2 months later.
Phase
Phase 3
Study type
Interventional
Enrollment
905
Allocation
Randomized
Ages
1 Day to 18 Years
Sex
All
01

Study 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.

Read the detailed description

This is a master protocol comprising a complex clinical trial with a stratification approach to allocate patients to randomized studies described in the master protocol or linked trials.

The overarching objective of the CHIP-AML22 study is to improve event-free survival (EFS) in children and adolescents with AML, as compared to NOPHO-DBH 2012.

The consortium strives to achieve the overarching aim by:

  1. Avoiding unnecessary toxicity. This will be investigated in a randomized setting (non-inferiority) by omitting a third standard-of-care consolidation course for standard-risk patients (4 versus 5 courses of chemotherapy).
  2. Introducing quizartinib as FLT3-inhibitor in addition to the first three sequential chemotherapy courses for all patients with FLT3-ITD/NPM1wt, and as post-SCT continuation treatment for the subset of patients that have MRD ≥0.1% after course 1 or at any time-point later on (historical comparison, higher efficacy).
  3. Refining risk-group adapted treatment, by classifying patients with KMT2A-rearrangement (except KMT2A/MLLT3) and MRD≥0.1% in BM after course 1 as high-risk (historical comparison, higher efficacy), as well as patients with the RAM-phenotype and/or CBFA2T3::GLIS2 fusion (historical comparison, higher efficacy). High-risk (non-FLT3-ITD/NPM1wt patients) will also be concluded for patients having ≥15% leukemic cells in BM after course 1, or ≥0.1-5% after course 2. Refractory disease will be defined as ≥5% leukemic cells in bone marrow after 2 courses of induction treatment, or disease elsewhere, or both.
  4. Recommending the use of the cardioprotective drug dexrazoxane in all courses incorporating an anthracycline or mitoxantrone (exploratory objective, no statistical design), with the aim to prevent cardiotoxicity.
  5. To assess if adding gemtuzumab ozogamicin to the first induction course results in better anti-leukemic efficacy in CD33-positive AML patients. Children with FLT3-ITD/NPM1wt are not eligible for this randomization.
  6. To explore health-related Quality of Life during and after completion of treatment by using short questionnaires (exploratory objective, no statistical design).
02

Conditions studied

  • Acute Myeloid Leukemia in Children
03

In context

Lead sponsor

Princess Maxima Center for Pediatric Oncology is the lead sponsor of 15 studies on the registry; 13 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
1 Day to 18 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

General inclusion criteria for CHIP-AML22/Master:

Patients are eligible for the study if they fulfil all four criteria below:

  1. Newly diagnosed AML as defined by the diagnostic criteria in section 8.1. Note that different blast thresholds may apply for different genetic abnormalities in case of low blast percentages. The origin of AML must be de novo (not secondary to bone marrow failure or therapy-related).
  2. Age ≥ day and ≤18 years old at initial diagnosis.
  3. Written informed consent/assent from patients and/or from parents or legal guardians for minor patients, according to local law and regulations. Informed consent should ideally be obtained before day 7 of induction course 1, as patients that are eligible for the linked quizartinib trial should be enrolled before the end of induction course 1, and in view of the planned Mylotarg® randomisation. Thus, standard of care diagnostics and induction treatment may be started before informed consent has been obtained.
  4. Able to comply with scheduled follow-up and with management of toxicity.

Additional inclusion criteria for Ri randomization

  1. CD33 positivity of leukemic blasts as measured by flow cytometry at diagnosis (bone marrow aspirate and/or peripheral blood).
  2. Informed consent for participation in randomization Ri

Additional inclusion criteria for Rc randomization

  1. Patients included in the CHIP-AML22 protocol and stratified to Standard Risk Group according to the stratification algorithm of the protocol
  2. Informed consent for participation in randomization Rc

General exclusion criteria for CHIP-AML22/Master

Patients are excluded if any of the criteria below are present:

  1. Previous chemotherapy or radiotherapy. This includes patients with therapy-related AML after previous cancer therapy. These patients may be treated according to the master protocol but will not be part of the formal study population, and data of these patients will not be collected.
  2. Patients with a (known) germline predisposition for bone marrow failure, like Fanconi anemia.
  3. Myeloid Leukemia of Down syndrome (ML-DS). Patients with ML-DS are recommended to be treated according to the international ML-DS protocol. Patients with AML and DS older than 5 years who often lack GATA1 mutation and do not have typical myeloid leukemia of DS may be treated according to the master protocol but will not be part of the formal study population, hence data of these patients will not be collected.
  4. Acute promyelocytic leukemia (APL).
  5. Myelodysplastic syndrome (MDS).
  6. Juvenile Myelomonocytic Leukemia (JMML).
  7. Known intolerance to any of the chemotherapeutic drugs in the protocol.
  8. Evidence of cardiac dysfunction (shortening fraction below 28%).
  9. Pregnant or lactating patients, or sexually active female patients of childbearing potential not willing to use an highly effective method of contraception for the duration of study therapy and up to 7 months after the completion of all study therapy.
  10. Sexually active, fertile male patients, not willing to use an effective method of contraception, for the duration of study therapy, and up to 6 months after the completion of all study therapy.
  11. Concomitant administration of any other experimental drug under investigation, or concurrent treatment with any other anti-cancer therapy other than specified in this protocol or in one of the trials linked to this Master protocol, is not allowed.
  12. Patients who in the opinion of the investigator, may not be able to comply with the study requirements of the study.
  13. Patients with known active hepatitis B, hepatitis C, or HIV infection.
  14. Patients for whom informed consent was not obtained.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
905 participants (estimated)

Study arms

  • Active comparator
    Standard arm Rc

    3 consolidation courses (HAM + HA3E + FLA)

    Drug: Standard Intervention Rc

  • Experimental
    Investigational arm Rc

    2 consolidation courses (HAM + FLA)

    Drug: Investigational Intervention Rc

  • Active comparator
    Standard arm Ri

    No addition om gemtuzumab ozogamicin (GO) to the first induction course of CD33-positive AML

    Drug: Standard Intervention Ri

  • Experimental
    Investigational arm Ri

    Addition om gemtuzumab ozogamicin (GO) to the first induction course of CD33-positive AML

    Drug: Investigational Intervention Ri

Interventions

  • DrugStandard Intervention Rc

    3 consolidation courses (HAM + HA3E + FLA)

  • DrugInvestigational Intervention Rc

    2 consolidation courses (HAM + FLA)

  • DrugStandard Intervention Ri

    No addition of GO to first induction course

  • DrugInvestigational Intervention Ri

    Addition of GO to first induction course

06

What researchers measure

Primary outcomes

  1. Overarching primary objective

    Event Free Survival (EFS)

    Time frame: 5 years

  2. Primary objective Randomisation Consolidation

    Disease Free Survival (DFS)

    Time frame: 5 years

  3. Primary objective Randomisation Induction

    MRD \<0.1% leukemic cells in the BM

    Time frame: 5 years

Secondary outcomes

  1. Overarching secondary objective - efficacy 1

    • Bone marrow blast counts by morphology and multicolor flow cytometry (MFCM) after course #1 and #2 and before allo-SCT

    Time frame: 8 months

  2. Overarching secondary objective - efficacy 2

    ORR (CR, CRp, and CRi) and morphologic leukemia-free state (MLFS) rates after course #1 and #2;

    Time frame: 3 months

  3. Overarching secondary objective - efficacy 3

    MRD negativity after course #1 and #2 and before allo-SCT

    Time frame: 8 months

  4. Overarching secondary objective - efficacy 4

    Absolute MRD levels after course #1 and #2 and before allo-SCT

    Time frame: 8 months

  5. Overarching secondary objective - efficacy 5

    • OS

    Time frame: 5 years

  6. Overarching secondary objective - efficacy 6

    • DFS

    Time frame: 5 years

  7. Overarching secondary objective - efficacy 7

    • CIR

    Time frame: 5 years

  8. Overarching secondary objective - toxicity 1

    • Cumulative toxicity, defined as the total of all grades AEs over time, which are graded by NCI CTCAE version 5.0.

    Time frame: 5 years

  9. Overarching secondary objective - toxicity 2

    • NRM.

    Time frame: 5 years

  10. Secondary objective Randomisation consolidation - safety 1

    • Cumulative toxicity, defined as the total of grade ≥3 AESIs over time, which are graded by NCI CTCAE version 5.0.

    Time frame: 8 months

  11. Secondary objective Randomisation consolidation - safety 2

    • NRM.

    Time frame: 5 years

  12. Secondary objective Randomisation consolidation - healthcare resources

    Cumulative Hospitalized Days

    Time frame: 1 year

  13. Secondary objective Randomisation consolidation - efficacy 1

    • OS

    Time frame: 5 years

  14. Secondary objective Randomisation consolidation - efficacy 2

    • CIR

    Time frame: 5 years

07

Study locations

1 of 1 sites recruiting
  • Princess Máxima Center for pediatric oncology
    Utrecht, Utrecht 3584 CS, Netherlands
    • Gertjan Kaspers, Prof. Dr. · Contact
    • Bianca Goemans, MD, PhD · Principal investigator
    Recruiting
08

References and documents

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 ↗

Individual participant data

Plan to share: Yes — All individual participant data will be used to generate a publication

Supporting information: Csr

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 5, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05994690
Lead sponsor
Princess Maxima Center for Pediatric Oncology
Collaborators
European Commission
Responsible party
Sponsor
First posted
Aug 16, 2023
Start date
Jul 14, 2023
Primary completion
Mar 2031 (estimated)
Completion
Dec 2035 (estimated)
Last update
Aug 5, 2025

Study contacts

Renske Benedictus
Contact
CHIP-AML22@prinsesmaximacentrum.nl
+31889727272
Gertjan Kaspers, Prof. Dr.
study chair · Pediatric Oncologist
Michel Zwaan, Prof. Dr.
study director · Head Trial and Data Center

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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