International Study for Treatment of High Risk Childhood Relapsed ALL 2010 A Randomized Phase II Study Conducted by the Resistant Disease Committee of the International Berlin, Frankfurt, Münster (BFM) Study Group
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 15
- 主要终点
- Rate of Complete Remission
研究概览
简要总结
The main goal of this study is to improve the outcome of children and adolescents with acute lymphoblastic leukemia with high risk first relapse by optimization of treatment strategies within a large international trial and the integration of new agents.
详细描述
Though survival of children with acute lymphoblastic leukemia (ALL) has considerably improved over the past few decades, relapsed ALL remains a leading cause of mortality in children with cancer. Risk has been defined by the International (I) Berlin, Frankfurt, Münster (BFM) Study Group (SG) based on duration of first remission, immunophenotype of malignant clone, and site of relapse. Patients classified as high risk (HR) by these criteria have poor response rates to standard induction therapy, high rates of subsequent relapse and require an allogeneic hematopoetic stem cell transplantation (allo-HSCT) for consolidation of 2nd remission. Over the last decade members of the I-BFM-SG have investigated the use of different combinations of conventional cytotoxic agents. Even with allo-HSCT, none of these approaches have improved outcome above 40%. Therefore, for HR patients there is a need to investigate the curative potential of new agents combined with systemic therapy. The proteasome inhibitor bortezomib has shown synergistic activity with acceptable toxicity when combined with corticosteroids, anthracyclines and alkylating agents in adult patients with cancer as well as with dexamethasone, doxorubicin, vincristine and polyethylene glycol (PEG) asparaginase in children with refractory or relapsed ALL. In the I-BFM-SG International Study for Treatment of High Risk Childhood Relapsed ALL (IntReALL) HR 2010 study, the potential of Bortezomib combined with a modified ALL relapse protocol 3 (R3) backbone as induction regimen for HR patients to improve complete 2nd remission (CR2) rates will be investigated in a randomized phase II design. Induction is followed by conventional intensive consolidation. After termination of the trial patients may be subjected to an investigational window, before all of them receive allo-HSCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Morphologically confirmed diagnosis of 1st relapsed precursor B-cell or T-cell ALL
- •Children less than 18 years of age at date of inclusion into the study
- •Meeting HR criteria any BM relapse, early/very early isolated BM relapse, very early isolated/combined extramedullary relapse)
- •Patient enrolled in a participating centre
- •Written informed consent
- •Start of treatment falling into the study period
- •No participation in other clinical trials 30 day prior to study enrolment that interfere with this protocol, except trials for primary ALL
排除标准
- •Breakpoint cluster region-Abelson (BCR-ABL)/ t(9;22) positive ALL
- •Pregnancy or positive pregnancy test (urine sample positive for β-humane choriongonadotropin (HCG) > 10 U/l)
- •Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 12 months after end of anti-leukemic therapy
- •Breast feeding
- •Relapse post allogeneic stem-cell transplantation
- •Neuropathy > II°
- •The whole protocol or essential parts are declined either by patient himself/herself or the respective legal guardian
- •Objection to the study participation by a minor patient, able to object
- •Any patient being dependent on the investigator
- •No consent is given for saving and propagation of pseudonymized medical data for study reasons
- •Severe concomitant disease that does not allow treatment according to the protocol at the investigator's discretion (e.g. malformation syndromes, cardiac malformations, metabolic disorders)
- •Subjects unwilling or unable to comply with the study procedures
- •Subjects who are legally detained in an official institute
研究组 & 干预措施
Arm HR-B
Induction: Backbone ALL R3 + Bortezomib
干预措施: Bortezomib (Drug)
Arm HR-A
Induction: Backbone ALL R3
结局指标
主要结局
Rate of Complete Remission
时间窗: Week 4
Rate of complete second remission (CR2) quantified by cytology after induction with standard chemotherapy + bortezomib (arm B) compared with standard chemotherapy (arm A).
次要结局
- Overall Survival(Year 3)
- Minimal Residual Disease Load(Week 15)
- Toxicity of induction classified with the COMMON TOXICITY CRITERIA (CTC)(At induction up to week 5)
- Minimal Residual Disease Reduction (MRD)(Week 4)
- Minimal Residual Disease (MRD)(Week 15)
- Complete Remission/Minimal Residual Disease Rates During Consolidation(Week 5, 8, 11, 15)
- Event-free Survival(Year 3)
研究者
PD Dr. Arend von Stackelberg
Prinicipal Investigator
Charite University, Berlin, Germany