2023-508968-30-00招募中3 期
Newly Diagnosed Adult Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ALL). Sequential Treatment with Ponatinib and the Bispecific Monoclonal Antibody Blinatumomab vs Chemotherapy and Imatinib. ALL2820
Fondazione Gimema Franco Mandelli Onlus77 个研究点 分布在 1 个国家目标入组 236 人开始时间: 2024年10月1日最近更新:
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 236
- 试验地点
- 77
- 主要终点
- The primary endpoint of this study is to evaluate the efficacy of a sequential approach based on the administration of Ponatinib plus and Blinatumomab vs chemotherapy combined with Imatinib, in terms of (EFS), a composite endpoint, with events defined as: non achievement of MRD negativity (CMR or PNQ), deaths for any reason, toxicity and resistance (due or not to an ABL1 mutation development) in adult Ph+ ALL (=18 years, no upper age limit).
研究概览
简要总结
To explore the efficacy of a front-line chemo-free strategy based on the administration of Ponatinib plus steroids as induction treatment, followed by the infusion of Blinatumomab as consolidation in adult Ph+ ALL (=18 years, no upper age limit), and to compare it with a chemotherapy scheme combined with Imatinib (control arm), in terms of event-free survival (EFS), a composite endpoint, with events defined as: non achievement of MRD negativity (CMR or PNQ), deaths for any reason, toxicity and resistance (due or not to an ABL1 mutation development) in adult Ph+ ALL (=18 years, no upper age limit).
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Signed written informed consent according to ICH/EU/GCP and national local laws.
- •Negative pregnancy test in women of childbearing potential.
- •Bone marrow specimen from primary diagnosis available.
- •Newly diagnosed adult B-precursor Ph+ ALL patients.
- •WHO performance status less or equal to
- •Age greater or equal to18 years, with no upper age limit.
- •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 and serum lipase less or equal to1.5 x ULN.
- •Normal cardiac function.
- •No evidence of CNS leukemia at blinatumomab start.
- •Negative HIV test, negative hepatitis B (HBsAg) and hepatitis C virus (anti-HCV) test.
排除标准
- •History of or current relevant CNS pathology (ongoing grade =2 epilepsy, seizure, paresis, aphasia, clinically relevant apoplexia, severe brain injuries, dementia, Parkinson’s disease, organic brain syndrome, psychosis).
- •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 condition 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.
- •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 Ponatinib. - Angina pectoris.
- •Other clinically significant vascular and 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 Ponatinib (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
- •Uncontrolled hypertriglyceridemia (triglycerides >450 mg/dL).
- •Taking medications that are known to be associated with Torsades de Pointes and medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib.
- •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.
结局指标
主要结局
The primary endpoint of this study is to evaluate the efficacy of a sequential approach based on the administration of Ponatinib plus and Blinatumomab vs chemotherapy combined with Imatinib, in terms of (EFS), a composite endpoint, with events defined as: non achievement of MRD negativity (CMR or PNQ), deaths for any reason, toxicity and resistance (due or not to an ABL1 mutation development) in adult Ph+ ALL (=18 years, no upper age limit).
The primary endpoint of this study is to evaluate the efficacy of a sequential approach based on the administration of Ponatinib plus and Blinatumomab vs chemotherapy combined with Imatinib, in terms of (EFS), a composite endpoint, with events defined as: non achievement of MRD negativity (CMR or PNQ), deaths for any reason, toxicity and resistance (due or not to an ABL1 mutation development) in adult Ph+ ALL (=18 years, no upper age limit).
次要结局
- DFS at 1 and 3 years.
- OS at 1 and 3 years.
- CIR.
- Safety profile. Safety profile in terms of incidence of grade =3 CTC-NCI side effects and toxicities.
- The feasibility of patients’ stratification to allo-SCT allocation on the basis of a refined MRD evaluation and on the presence/absence of IKZF1-plus).
- Capability of Blinatumomab to further reduce the MRD levels after Ponatinib induction.
- CMR or PNQ duration.
- Comparison of patients’ quality of life (QoL) profiles over time by randomization arms.
研究者
GIMEMA Centro Dati
Scientific
Fondazione Gimema Franco Mandelli Onlus
研究点 (77)
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