D-ALBA Front-Line Sequential Treatment of Adult Philadelphia Chromosome Positive (Ph+) Acute Lymphoblastic Leukemia (ALL) Patients With Dasatinib and the Bispecific Monoclonal Antibody Blinatumomab
试验速览
- 阶段
- 2 期
- 入组人数
- 60
- 试验地点
- 34
- 主要终点
- Number of patients who achieve Minimal Residual Disease (MRD) negativity upon treatment
研究概览
简要总结
This study aims at exploring the activity of a frontline approach based on dasatinib plus steroids administration as induction treatment, followed by the infusion of Blinatumomab, in adult Ph+ ALL.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed adult B-precursor Ph+ ALL patients.
- •Age greater or equal to18 years,
- •Signed written informed consent according to ICH/EU/GCP and national local laws.
- •ECOG Performance Status 0 or 1 and/or WHO performance status less or equal to
- •Renal and hepatic function as defined below:
- •AST (GOT), ALT (GPT), and AP <2 x upper limit of normal (ULN).
- •Total bilirubin <1.5 x ULN.
- •Creatinine clearance equal or greater than 50 mL/min.
- •Pancreatic function as defined below:
- •Serum amylase less or equal to 1.5 x ULN
- •Serum lipase less or equal to1.5 x ULN.
- •Normal cardiac function.
- •Negative HIV test, negative HBV DNA and HCV RNA.
- •Negative pregnancy test in women of childbearing potential.
- •Bone marrow specimen from primary diagnosis available.
排除标准
- •History of or current relevant CNS pathology (current ≥grade 2 epilepsy, seizure, paresis, aphasia, clinically relevant apoplexia, severe brain injuries, dementia, Parkinson's disease, organic brain syndrome, psychosis).
- •Impaired cardiac function, including any one of the following:
- •LVEF <45% as determined by MUGA scan or echocardiogram.
- •Complete left bundle branch block.
- •Use of a cardiac pacemaker.
- •ST depression of >1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads.
- •Congenital long QT syndrome.
- •History of or presence of significant ventricular or atrial arrhythmia.
- •Clinically significant resting bradycardia (<50 beats per minute).
- •QTc >450 msec on screening ECG (using the QTcF formula).
- •Right bundle branch block plus left anterior hemiblock, bifascicular block.
- •Myocardial infarction within 3 months prior to starting Dasatinib.
- •Angina pectoris.
- •Other clinically significant heart disease (e.g., congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen).
- •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of Dasatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- •History of or current autoimmune disease.
- •Systemic cancer chemotherapy within 2 weeks prior to study.
- •Known hypersensitivity to immunoglobulins or to any other component of the study drug formulation.
- •Active malignancy other than ALL with the exception of basal cell or squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix.
- •Active infection, any other concurrent disease or medical conditions that are deemed to interfere with the conduct of the study as judged by the investigator.
- •Nursing women or women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least 3 months thereafter or male patients not willing to ensure effective contraception during participation in the study and at least three months thereafter.
研究组 & 干预措施
Treatment
Adult Ph+ ALL (≥18 years old, with no upper age limit) patients will begin treatment with Dasatinib, 140 mg/day, from day 1 to day +84. Prednisone (PDN) will be administered from day -6 to day +0 (during which the presence of the BCR/ABL1 alteration will be established), at escalating doses up to 60 mg/m2; PDN will be continued up to day +24 and progressively tapered up to day +31.
HLA typing will be performed immediately after the diagnosis for eligible patients.
MRD will be evaluated by RT-PCR at fixed time points (days +22, +45, +57) during the induction and at day +85, the latter for molecular response evaluation.
干预措施: Dasatinib (Drug)
Treatment
Adult Ph+ ALL (≥18 years old, with no upper age limit) patients will begin treatment with Dasatinib, 140 mg/day, from day 1 to day +84. Prednisone (PDN) will be administered from day -6 to day +0 (during which the presence of the BCR/ABL1 alteration will be established), at escalating doses up to 60 mg/m2; PDN will be continued up to day +24 and progressively tapered up to day +31.
HLA typing will be performed immediately after the diagnosis for eligible patients.
MRD will be evaluated by RT-PCR at fixed time points (days +22, +45, +57) during the induction and at day +85, the latter for molecular response evaluation.
干预措施: Blinatumomab (Drug)
结局指标
主要结局
Number of patients who achieve Minimal Residual Disease (MRD) negativity upon treatment
时间窗: After 11 months from study entry
In particular, after 2 cycles of blinatumomab. Minimal Residual Disease (MRD) negativity is intended as Complete Molecular Remission (CMR)
次要结局
- Number of months of the CMR(At 12 and 24 months)
- Number of patients at Complete Molecular Response (CMR)(At day +22, +45, +57 and +85 from study entry)
- Number of patients in Overall Survival (OS)(At 12 and 24 months)
- Number of grade >3 adverse events(At 12 and 24 months)
- Number of patients completing the 2 cycles of blinatumomab and alive in first complete hematologic remission (CHR)(From day +85 at 12 months)