- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05994690
CHIP-AML22/Master: An Open Label Complex Clinical Trial in Newly Diagnosed Pediatric de Novo AML Patients
An Open Label Complex Clinical Trial in Newly Diagnosed Pediatric de Novo AML Patients - a Study by the NOPHO-DB-SHIP Consortium, Master Protocol
Study Overview
Status
Conditions
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:
- 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).
- 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).
- 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.
- 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.
- 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.
- To explore health-related Quality of Life during and after completion of treatment by using short questionnaires (exploratory objective, no statistical design).
Study Type
Enrollment (Estimated)
Phase
- Phase 3
Contacts and Locations
Study Contact
- Name: Renske Benedictus
- Phone Number: +31889727272
- Email: CHIP-AML22@prinsesmaximacentrum.nl
Study Locations
-
-
-
Utrecht, Netherlands, 3584 CS
- Recruiting
- Princess Maxima Center for pediatric oncology
-
Contact:
- Gertjan Kaspers, Prof. Dr.
-
Principal Investigator:
- Bianca Goemans, MD, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
Description
General inclusion criteria for CHIP-AML22/Master:
Patients are eligible for the study if they fulfil all four criteria below:
- 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).
- Age ≥ day and ≤18 years old at initial diagnosis.
- 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.
- Able to comply with scheduled follow-up and with management of toxicity.
Additional inclusion criteria for Ri randomization
- CD33 positivity of leukemic blasts as measured by flow cytometry at diagnosis (bone marrow aspirate and/or peripheral blood).
- Informed consent for participation in randomization Ri
Additional inclusion criteria for Rc randomization
- Patients included in the CHIP-AML22 protocol and stratified to Standard Risk Group according to the stratification algorithm of the protocol
- 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:
- 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.
- Patients with a (known) germline predisposition for bone marrow failure, like Fanconi anemia.
- 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.
- Acute promyelocytic leukemia (APL).
- Myelodysplastic syndrome (MDS).
- Juvenile Myelomonocytic Leukemia (JMML).
- Known intolerance to any of the chemotherapeutic drugs in the protocol.
- Evidence of cardiac dysfunction (shortening fraction below 28%).
- 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.
- 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.
- 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.
- Patients who in the opinion of the investigator, may not be able to comply with the study requirements of the study.
- Patients with known active hepatitis B, hepatitis C, or HIV infection.
- Patients for whom informed consent was not obtained.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Standard arm Rc
3 consolidation courses (HAM + HA3E + FLA)
|
3 consolidation courses (HAM + HA3E + FLA)
|
Experimental: Investigational arm Rc
2 consolidation courses (HAM + FLA)
|
2 consolidation courses (HAM + FLA)
|
Active Comparator: Standard arm Ri
No addition om gemtuzumab ozogamicin (GO) to the first induction course of CD33-positive AML
|
No addition of GO to first induction course
|
Experimental: Investigational arm Ri
Addition om gemtuzumab ozogamicin (GO) to the first induction course of CD33-positive AML
|
Addition of GO to first induction course
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overarching primary objective
Time Frame: 5 years
|
Event Free Survival (EFS)
|
5 years
|
Primary objective Randomisation Consolidation
Time Frame: 5 years
|
Disease Free Survival (DFS)
|
5 years
|
Primary objective Randomisation Induction
Time Frame: 5 years
|
MRD <0.1% leukemic cells in the BM
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overarching secondary objective - efficacy 1
Time Frame: 8 months
|
• Bone marrow blast counts by morphology and multicolor flow cytometry (MFCM) after course #1 and #2 and before allo-SCT
|
8 months
|
Overarching secondary objective - efficacy 2
Time Frame: 3 months
|
ORR (CR, CRp, and CRi) and morphologic leukemia-free state (MLFS) rates after course #1 and #2;
|
3 months
|
Overarching secondary objective - efficacy 3
Time Frame: 8 months
|
MRD negativity after course #1 and #2 and before allo-SCT
|
8 months
|
Overarching secondary objective - efficacy 4
Time Frame: 8 months
|
Absolute MRD levels after course #1 and #2 and before allo-SCT
|
8 months
|
Overarching secondary objective - efficacy 5
Time Frame: 5 years
|
• OS
|
5 years
|
Overarching secondary objective - efficacy 6
Time Frame: 5 years
|
• DFS
|
5 years
|
Overarching secondary objective - efficacy 7
Time Frame: 5 years
|
• CIR
|
5 years
|
Overarching secondary objective - toxicity 1
Time Frame: 5 years
|
• Cumulative toxicity, defined as the total of all grades AEs over time, which are graded by NCI CTCAE version 5.0.
|
5 years
|
Overarching secondary objective - toxicity 2
Time Frame: 5 years
|
• NRM.
|
5 years
|
Secondary objective Randomisation consolidation - safety 1
Time Frame: 8 months
|
• Cumulative toxicity, defined as the total of grade ≥3 AESIs over time, which are graded by NCI CTCAE version 5.0.
|
8 months
|
Secondary objective Randomisation consolidation - safety 2
Time Frame: 5 years
|
• NRM.
|
5 years
|
Secondary objective Randomisation consolidation - healthcare resources
Time Frame: 1 year
|
Cumulative Hospitalized Days
|
1 year
|
Secondary objective Randomisation consolidation - efficacy 1
Time Frame: 5 years
|
• OS
|
5 years
|
Secondary objective Randomisation consolidation - efficacy 2
Time Frame: 5 years
|
• CIR
|
5 years
|
Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Gertjan Kaspers, Prof. Dr., Pediatric Oncologist
- Study Director: Michel Zwaan, Prof. Dr., Head Trial and Data Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 2023-504999-25-00
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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