Interfant-21 International Collaborative Treatment Protocol for Infants Under One Year With KMT2A-rearranged Acute Lymphoblastic Leukemia or Mixed Phenotype Acute Leukemia.
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 160
- 试验地点
- 252
- 主要终点
- Event free survival (EFS).
研究概览
简要总结
This study is a treatment protocol with blinatumomab for infants under 1 year old who are diagnosed with acute lymphoblastic leukemia with a specific unfavorable genetic alteration. The purpose of the study is to improve the outcome of this disease in infants.
详细描述
All infants that are eligible for this study and for whom the parents/legal representatives give informed consent will be enrolled in this study. All patients will receive one cycle of blinatumomab on top of the standard treatment backbone after induction therapy. Medium risk patients, that respond well to the 1st cycle will be treated with a 2nd cycle of blinatumomab replacing one chemo course after consolidation therapy. If they do not respond well enough they will be treated according to the current treatment standard. Minimal residual disease will be used to determine the response to blinatumomab. High risk patients will be eligible for allogeneic stem cell transplantation after the first blinatumomab cycle if they are Minimal Residual Disease (MRD) negative (defined as < 0.01%). Also medium risk patients with insufficient MRD response after induction or after the 1st cycle of blinatumomab will be allocated to high risk treatment and will be eligible for allogeneic stem cell transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Day 至 1 Year（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with newly diagnosed B- precursor ALL or B-cell MPAL (single lineage) according to the WHO classification of tumours of haematopoietic and lymphoid tissues (revised 4th edition 2017), with KMT2A-rearrangement.
- •≤ 365 days of age at the time of diagnosis of ALL.
- •Written informed consent of the parent(s) or other legally authorized guardian of the patient according to local law and regulations.
排除标准
- •for blinatumomab:
- •KMT2A-wildtype patients.
- •Multilineage MPAL
- •Age > 365 days at the time of diagnosis.
- •Down syndrome.
- •Relapsed ALL.
- •Treatment with systemic corticosteroids (equivalent prednisone >10 mg/m2/day) for more than one week and/or any chemotherapeutic agent in the 4-week interval prior to diagnosis. Patients who received corticosteroids by aerosol are eligible for the study.
- •If exclusion criteria for blinatumomab are met, the patient should be treated according to the protocol but without blinatumomab.
研究组 & 干预措施
High risk (HR)
Subject is defined as HR if < 6 months of age with WBC > 300 at diagnosis OR poor prednisone response. Also MR patients with end of induction MRD ≥ 1%, or MRD > 0.01% after the 1st cycle of blinatumomab, will be allocated to HR treatment. Subject gets 1 cycle of blinatumomab.
Thereafter patient is eligible for hematopoietic stem cell transplantation (HSCT) with or without experimental therapy in an investigational window.
干预措施: Blinatumomab (Drug)
Medium Risk (MR)
Subject is defined as MR if > 6months of age at diagnosis, OR < 6 months of age with White Blood cell Count (WBC) < 300 at diagnosis and good prednisone response. Subject gets 1st cycle of blinatumomab. If MRD is >0.01%, after 1st cycle of blinatumomab, subject will be allocated to HR treatment from that phase, and will be eligible for HSCT. If MRD is undetectable or < 0.01% after the 1st cycle of blinatumomab (TP2) patient will be eligible for replacement of MARMA by 2nd cycle of blinatumomab after receipt of lymphoid style consolidation (Protocol IB) or of myeloid style consolidation (ADE/MAE).
干预措施: Blinatumomab (Drug)
结局指标
主要结局
Event free survival (EFS).
时间窗: 5 years
The primary endpoint is EFS, defined as the time from diagnosis to resistance to induction, relapse, death from any cause or second malignancy (whichever occurs first), or time to last follow-up (censored) for patients without events.
次要结局
- Overall survival(8 years)
- CD19 (cluster of differentiation antigen 19) negative relapse(8 years)
- Myeloid lineage switches(8 years)
- Endpoints by risk group(8 years)
- Outcome for the entire study cohort and according to risk group(8 years)
- Minimal Residual Disease(8 years)
- Grade ≥3 adverse event(8 years)
- Grade ≥2 cardiac disorders(5 years)
- Overall survival after 1st relapse(8 years)