2023-504999-25-00招募中3 期
CHIP-AML22 Master protocol: An open label complex clinical trial in newly diagnosed pediatric de novo AML patients – a study by the NOPHO-DB-SHIP consortium Master Protocol
Prinses Maxima Centrum voor Kinderoncologie B.V.50 个研究点 分布在 12 个国家目标入组 675 人开始时间: 2023年10月27日最近更新:
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 675
- 试验地点
- 50
- 主要终点
- Primary endpoint of overarching objective: Event-free survival (EFS)
研究概览
简要总结
• Overarching objective: To improve the overall EFS for children and adolescents with newly diagnosed AML, compared to NOPHO-DBH AML-2012. • Induction randomization: To assess if adding GO to the first induction course results in better early anti-leukemic efficacy in CD33-positive AML patients, compared to no-GO. • Consolidation randomization: To demonstrate non-inferiority in disease-free survival of two courses of consolidation therapy, by omitting HA3E, as compared to three courses, in the entire standard-risk group eligible for this randomization.
研究设计
- 分配方式
- Randomized
- 主要目的
- Randomisation Induction
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 64 years（18-64 Years, 0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •Newly diagnosed AML. The origin of AML must be de novo (not secondary to bone marrow failure or therapy-related).
- •Age ≥1 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.
- •Able to comply with scheduled follow-up and with management of toxicity.
- •Additional inclusion criteria for the induction randomization: 1) CD33 positivity of leukemic blasts as measured by flow cytometry (mean fluorescence intensity; MFI) at diagnosis (bone marrow aspirate and/or peripheral blood). CD33 positivity is defined as a ratio of at least 10 (using the anti-CD33 clone P67.6) of the geometric MFI of CD33 for the ‘blast population’ divided by the MFI of the CD33 background signal of lymphocytes. 2) Informed consent for participation in randomization Ri.
- •Additional inclusion criteria for the consolidation 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.
排除标准
- •Previous chemotherapy or radiotherapy. This includes patient with therapy-related AML after previous cancer therapy.
- •Myelodysplastic syndrome (MDS).
- •Juvenile Myelomonocytic Leukemia (JMML).
- •Known intolerance to any of the chemotherapeutic drugs in the protocol.
- •Evidence of cardiac dysfunction (ejection fraction below 55%).
- •Pregnant or lactating patients, or sexually active female patients of childbearing potential not willing to use a highly effective method of contraception for the duration of study therapy and up to 7 months after the completion of all study therapy.
- •Additional exclusion criteria for the induction randomization: 1) Hypersensitivity to the active substance of GO or to any of the excipients listed in section 6.1 of the SPC of GO. 2) Patients with FLT3-ITD/NPM1wt that are participating in the linked quizartinib trial.
- •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, when the primary objective(s) is affected.
- •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.
- •Patients with a (known) germline predisposition for bone marrow failure, like Fanconi anemia.
- •Myeloid Leukemia of Down syndrome (MLDS).
- •Acute promyelocytic leukemia (APL).
结局指标
主要结局
Primary endpoint of overarching objective: Event-free survival (EFS)
Primary endpoint of overarching objective: Event-free survival (EFS)
Primary end point induction Randomization: • MRD <0.1% leukemic cells in the BM, as defined by flow cytometry, shortly before start of induction course 2 (BM1).
Primary end point induction Randomization: • MRD <0.1% leukemic cells in the BM, as defined by flow cytometry, shortly before start of induction course 2 (BM1).
Primary endpoint of consolidation Randomization: Disease-Free Survival (DFS)
Primary endpoint of consolidation Randomization: Disease-Free Survival (DFS)
次要结局
- Secondary end point overarching objective: • Bone marrow blast counts by morphology and multi-color flow cytometry (MFCM) after course #1 and #2 and before allo-SCT; ORR (CR, CRp, and CRi) and morphologic leukemia-free state (MLFS) rates after course #1 and #2; MRD negativity after course #1 and #2 and before allo-SCT; absolute MRD levels after course #1 and #2 and before allo-SCT. • OS • DFS • CIR.
- Secondary end point overarching objective: • Cumulative toxicity, defined as the total of all grades AEs over time, which are graded by NCI CTCAE version 5.0. • NRM.
- Secondary end point induction randomization: • Bone marrow blast counts by morphology and multi-color flow cytometry (MFCM) after course #1 and #2 and before allo-SCT; ORR (CR, CRp, and CRi) and morphologic leukemia-free state (MLFS) rates after course #1 and #2; MRD negativity after course #2 and before allo-SCT; absolute MRD levels after course and #2 and before allo-SCT. OS • DFS • EFS • CIR • OS
- Secondary end point induction randomization: • Cumulative toxicity, defined as the total of grade ≥3 AESIs over time, which are graded by NCI CTCAE version 5.0. • Adverse events (AEs), as characterized by type, frequency, severity (as graded using CTCAE, v5.0). • Serious adverse events (SAEs), as characterized by type, frequency, severity (as graded using CTCAE, v5.0). • NRM.
- Secondary end point consolidation randomization: 18)• Cumulative toxicity, defined as the as the total of grade ≥3 AESIs over time, which are graded by NCI CTCAE version 5.0. 19)• Non-relapse mortality (TRM).
- Secondary end point consolidation randomization: Cumulative Hospitalized Days
- Secondary end point consolidation randomization: •OS •CIR
研究者
Prof. Dr. Gertjan J.L. Kaspers
Scientific
Prinses Maxima Centrum voor Kinderoncologie B.V.
研究点 (50)
Loading locations...
相似试验
招募中
3 期
Open-Label followed by a Double-Blind, Placebo-Controlled Study to Investigate the Efficacy and Safety of Infigratinib in Children with HypochondroplasiaHypochondroplasia2024-516822-67-00Qed Therapeutics Inc.32
招募中
3 期
Study on chemotherapy and experimental drugs in patients with Philadelphia Chromosome positive and ABL-class Philadelphia Chromosome-Like B-cell Acute Lymphoblastic Leukemia2025-520982-39-00Universita Degli Studi Di Milano Bicocca20
尚未招募
1 期
A Study of ABSK061 to Assess Safety, Tolerability, Pharmacokinetics, and Efficacy in Children With AchondroplasiaAchondroplasiaNCT07297875Abbisko Therapeutics Co, Ltd110
招募中
2 期
FILOWM4-WaZaBi: "Open label phase 2 study evaluating the efficacy and tolerance of a zanubrutinib and BGB-11417 combination in patients previously treated for Waldenström macroglobulinemia"2023-505781-28-00French Innovative Leukemia Organization102
招募中
2 期
Efficacy of the Combination of Trimipramine and Atezolizumab With Bevacizumab in Patients With Recurrent Glioblastoma: a Phase 2 TrialGlioblastomaNCT07263438Centre Hospitalier Universitaire Vaudois59