AALL2131/EsPhALL2022, An International Pilot Study of Chemotherapy and Tyrosine Kinase Inhibitor with Blinatumomab in Patients with Newly Diagnosed Philadelphia Chromosome Positive or ABL-class Philadelphia Chromosome-Like B-cell Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 21
- 主要终点
- To estimate the 3-year event free survival (EFS) of children, adolescents, and young adults <25 years old with newly-diagnosed Ph+ B-ALL who are treated with a modified Berlin-Frankfurt-Münster (BFM) chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous dasatinib
研究概览
简要总结
- To estimate the 3-year event free survival (EFS) of children, adolescents, and young adults with newly-diagnosed Ph+ (BCR::ABL1-rearranged) B-ALL who are treated with a modified Berlin-Frankfurt-Münster (mBFM) chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous dasatinib.
- To estimate the 3-year EFS of children, adolescents, and young adults with newly-diagnosed ABL-class Ph-like B-ALL who are treated with a modified BFM chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous imatinib for those with PDGFRB gene fusions or dasatinib for those without PDGFRB gene fusions
- To describe the safety and toxicity profile (infections, mucositis, neurotoxicity, cytokine release syndrome, hypogammaglobulinemia, therapy delays > 14 days, and treatment-related mortality) for patients with Ph+ or ABL-class Ph-like B-ALL treated on this novel chemo-immunotherapy backbone with continuous TKI.
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
- •Patients must be >365 days and <18 years (for AIEOP-BFM), >365 days and <22 years (for COG) and >365 days and <46 years (for ALLTogether sites) at the time of enrollment.
- •Adequate liver function
- •Adequate cardiac function
- •Newly-diagnosed Ph+ or ABL-class Ph-like B-ALL. Leukemic blasts must express CD
- •ABL-class fusions are defined as rearrangements involving the following genes predicted to be sensitive to imatinib and/or dasatinib: ABL1, ABL2, CSF1R, and PDGFRB.
- •Evidence of BCR::ABL1 should be documented by a clinically-validated assay prior to study entry on Day 15 from the first dose of vincristine during Induction therapy.
- •Patients with Ph+ B-ALL must have previously started Induction therapy, which includes vincristine, a corticosteroid, pegaspargase or calaspargase pegol, with or without anthracycline, and/or other standard cytotoxic chemotherapy.
- •Patients with Ph+ B-ALL have not received more than 14 days of systemic Induction therapy beginning with the first Induction dose of vincristine.
- •Patients with ABL-class Ph-like B-ALL must have previously completed 4 or 5 weeks of multiagent Induction chemotherapy
- •Patients may have started either imatinib or dasatinib prior to study entry but should have received no more than 14 days of TKI for Ph+ B-ALL or no more than 35 days of TKI for ABL-class Ph-like B-ALL.
- •Patients must have a performance status corresponding to ECOG scores of ≤2 or Karnofsky and Lansky performance scores ≥50%. Use Karnofsky for patients >16 years of age and Lansky for patients ≤ 16 years of age.
- •Adequate renal function
排除标准
- •Known history of chronic myeloid leukemia (CML)
- •Patients with significant central nervous system pathology that would preclude treatment with blinatumomab, including history of severe neurologic disorder or autoimmune disease with CNS involvement
- •HIV-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of treatment
- •ABL-class Ph-like B-ALL who are CNS2 or CNS3 at end of Induction phase.
- •ALL developing after a previous cancer treated with cytotoxic chemotherapy
- •Active, uncontrolled infection or active systemic illness that requires ongoing vasopressor support or mechanical ventilation
- •Down syndrome (trisomy 21)
- •Pregnancy and breast feeding
- •Prior treatment with TKIs before study entry with the exception of imatinib or dasatinib
- •Patients with congenital long QT syndrome, history of ventricular arrhythmias, or heart block
- •Patients with known Charcot-Marie-Tooth disease
结局指标
主要结局
To estimate the 3-year event free survival (EFS) of children, adolescents, and young adults <25 years old with newly-diagnosed Ph+ B-ALL who are treated with a modified Berlin-Frankfurt-Münster (BFM) chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous dasatinib
To estimate the 3-year event free survival (EFS) of children, adolescents, and young adults <25 years old with newly-diagnosed Ph+ B-ALL who are treated with a modified Berlin-Frankfurt-Münster (BFM) chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous dasatinib
To estimate the 3-year EFS of children, adolescents, and young adults <25 years old with newly-diagnosed ABL-class Ph-like B-ALL who are treated with a modified BFM chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous imatinib for those with PDGFRB fusions or dasatinib for those without PDGFRB fusions
To estimate the 3-year EFS of children, adolescents, and young adults <25 years old with newly-diagnosed ABL-class Ph-like B-ALL who are treated with a modified BFM chemotherapy backbone that incorporates three cycles of blinatumomab without traditional consolidation chemotherapy in combination with continuous imatinib for those with PDGFRB fusions or dasatinib for those without PDGFRB fusions
To describe the safety and toxicity profile (infections, mucositis, neurotoxicity, cytokine release syndrome, hypogammaglobulinemia, therapy delays > 14 days, and treatment-related mortality) for patients with Ph+ or ABL-class Ph-like B-ALL treated on this novel chemo-immunotherapy backbone with continuous TKI.
To describe the safety and toxicity profile (infections, mucositis, neurotoxicity, cytokine release syndrome, hypogammaglobulinemia, therapy delays > 14 days, and treatment-related mortality) for patients with Ph+ or ABL-class Ph-like B-ALL treated on this novel chemo-immunotherapy backbone with continuous TKI.
次要结局
- To estimate the 3-year overall survival (OS) of patients with Ph+ and ABL-class Ph-like B-ALL, respectively.
- To estimate the 3-year EFS, disease-free survival (DFS), cumulative incidence rates (CIR) of relapse, and treatment related mortality (TRM), and OS of patients with ABL-class Ph-like B-ALL stratified by their underlying ABL-class fusion subtypes
- To describe rates of EOC/TP2 MRD negativity defined as <1x10-4 or <0.01% for patients with ABL-class Ph-like B-ALL collectively and based on their ABL-class fusion subtypes.
研究者
Adriana Balduzzi
Scientific
Universita Degli Studi Di Milano Bicocca