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

NCT ID: NCT05994690

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 905 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-14
• Study Completion Date: 2035-12-31

Brief 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.

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).

Conditions

Acute Myeloid Leukemia in Children

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard arm Rc

3 consolidation courses (HAM + HA3E + FLA)

Group Type: ACTIVE_COMPARATOR

Standard Intervention Rc

Intervention Type: DRUG

3 consolidation courses (HAM + HA3E + FLA)

Investigational arm Rc

2 consolidation courses (HAM + FLA)

Group Type: EXPERIMENTAL

Investigational Intervention Rc

Intervention Type: DRUG

2 consolidation courses (HAM + FLA)

Standard arm Ri

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

Group Type: ACTIVE_COMPARATOR

Standard Intervention Ri

Intervention Type: DRUG

No addition of GO to first induction course

Investigational arm Ri

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

Group Type: EXPERIMENTAL

Investigational Intervention Ri

Intervention Type: DRUG

Addition of GO to first induction course

Interventions

Standard Intervention Rc

3 consolidation courses (HAM + HA3E + FLA)

Intervention Type: DRUG

Investigational Intervention Rc

2 consolidation courses (HAM + FLA)

Intervention Type: DRUG

Standard Intervention Ri

No addition of GO to first induction course

Intervention Type: DRUG

Investigational Intervention Ri

Addition of GO to first induction course

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

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

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

Exclusion Criteria

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.

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Commission

OTHER

Sponsor Role: collaborator

Princess Maxima Center for Pediatric Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gertjan Kaspers, Prof. Dr.

Role: STUDY_CHAIR

Pediatric Oncologist

Michel Zwaan, Prof. Dr.

Role: STUDY_DIRECTOR

Head Trial and Data Center

Locations

Princess Máxima Center for pediatric oncology

Utrecht, Utrecht, Netherlands

Site Status: RECRUITING

Countries

Netherlands

Central Contacts

Renske Benedictus

Role: CONTACT

CHIP-AML22@prinsesmaximacentrum.nl

+31889727272

Facility Contacts

Gertjan Kaspers, Prof. Dr.

Role: primary

Other Identifiers

2023-504999-25-00

Identifier Type: -

Identifier Source: org_study_id