CHIP-AML22/Master: An Open Label Complex Clinical Trial in Newly Diagnosed Pediatric de Novo AML Patients
- Conditions
- Acute Myeloid Leukemia in Children
- Interventions
- Drug: Standard Intervention RcDrug: Investigational Intervention RcDrug: Standard Intervention RiDrug: Investigational Intervention Ri
- Registration Number
- NCT05994690
- Lead Sponsor
- Princess Maxima Center for Pediatric Oncology
- 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).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 905
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard arm Rc Standard Intervention Rc 3 consolidation courses (HAM + HA3E + FLA) Investigational arm Rc Investigational Intervention Rc 2 consolidation courses (HAM + FLA) Standard arm Ri Standard Intervention Ri No addition om gemtuzumab ozogamicin (GO) to the first induction course of CD33-positive AML Investigational arm Ri Investigational Intervention Ri Addition om gemtuzumab ozogamicin (GO) to the first induction course of CD33-positive AML
- Primary Outcome Measures
Name Time Method Overarching primary objective 5 years Event Free Survival (EFS)
Primary objective Randomisation Consolidation 5 years Disease Free Survival (DFS)
Primary objective Randomisation Induction 5 years MRD \<0.1% leukemic cells in the BM
- Secondary Outcome Measures
Name Time Method Overarching secondary objective - efficacy 5 5 years • OS
Overarching secondary objective - efficacy 1 8 months • Bone marrow blast counts by morphology and multicolor flow cytometry (MFCM) after course #1 and #2 and before allo-SCT
Overarching secondary objective - efficacy 2 3 months ORR (CR, CRp, and CRi) and morphologic leukemia-free state (MLFS) rates after course #1 and #2;
Overarching secondary objective - efficacy 3 8 months MRD negativity after course #1 and #2 and before allo-SCT
Overarching secondary objective - efficacy 4 8 months Absolute MRD levels after course #1 and #2 and before allo-SCT
Overarching secondary objective - efficacy 6 5 years • DFS
Overarching secondary objective - efficacy 7 5 years • CIR
Overarching secondary objective - toxicity 1 5 years • Cumulative toxicity, defined as the total of all grades AEs over time, which are graded by NCI CTCAE version 5.0.
Overarching secondary objective - toxicity 2 5 years • NRM.
Secondary objective Randomisation consolidation - safety 1 8 months • Cumulative toxicity, defined as the total of grade ≥3 AESIs over time, which are graded by NCI CTCAE version 5.0.
Secondary objective Randomisation consolidation - safety 2 5 years • NRM.
Secondary objective Randomisation consolidation - healthcare resources 1 year Cumulative Hospitalized Days
Secondary objective Randomisation consolidation - efficacy 1 5 years • OS
Secondary objective Randomisation consolidation - efficacy 2 5 years • CIR
Trial Locations
- Locations (1)
Princess Máxima Center for pediatric oncology
🇳🇱Utrecht, Netherlands