A Phase III Study, Randomized, to Evaluate the Reduction of Chemotherapy Intensity in Association With Nilotinib (Tasigna®) in Philadelphia Chromosome-positive (Ph+) ALL of Young Adults (18-59 Years Old) (GRAAPH-2014)

Assistance Publique - Hôpitaux de Paris1 个研究点分布在 1 个国家目标入组 265 人开始时间: 2016年4月最近更新: 2019年10月21日

适应症

干预措施

试验速览

阶段: 3 期
状态: 招募中
发起方: Assistance Publique - Hôpitaux de Paris
入组人数: 265
试验地点: 1
主要终点: Major Molecular Response (MMolR)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The Primary objective is to assess the non-inferiority of the experimental arm (arm B) compared to the control arm (arm A) in terms of Major Molecular Response (MMolR) after the 4th cycle (MRD4) in patients aged 18-59 years old with de novo Philadelphia positive (Ph+) acute lymphoblastic leukemia (ALL)

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: 18 Years 至 59 Years（Adult）
性别: All
接受健康志愿者: 否

入选标准

•Whose blood and bone marrow explorations have been completed before the steroids prephase
•Aged 18-59 years old with newly-diagnosed non previously treated Ph+ ALL according to WHO 2008 criteria (confirmed diagnosis of the Philadelphia chromosome defined by the reciprocal translocation of chromosomes 9 and 22, t(9;22) and/or presence of the BCR-ABL molecular maker)
•With ≥ 20% bone marrow blasts
•With Eastern Cooperative Oncology Group (ECOG) Performans Status ≤ 3
•With or without central nervous system (CNS) or testis involvement
•Without evolving cancer (except basal cell carcinoma of the skin or "in situ" carcinoma of the cervix) or its chemo- or radio-therapy should be finished at least since 6 months.
•Having received no previous treatment for this hematological disease (including IT injection)
•Having signed written informed consent
•With efficient contraception for women of childbearing age (excluding estrogens and IUD)
•With health insurance coverage
•Who have received (or being receiving) the recommended steroid prephase.
•Note 1: Secondary ALL (antecedent of chemo- or radio-therapy) can be included Note 2: In case of high vascular risk (see section "study management") the patient will not be able to receive nilotinib unless an ultra sound Doppler of the neck and lower limbs has been performed during the pre-phase and treatment validated by the medical coordinators of the protocol via the secretariat.

排除标准

•Previously treated with Tyrosine Kinase Inhibitor (TKI)
•With another active malignancy
•With general or visceral contra-indication to intensive therapy (except if considered related to the ALL):
•Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2.5 x upper limit of normal range (ULN)
•Total bilirubin > 1.5 x ULN
•Creatinine > 1.5 x ULN or creatinine clearance <50 mL/mn
•Serum amylase or lipase > 1.5 x ULN or antecedents of acute pancreatitis
•With heart failure, including at least one of the following criteria:
•Left ventricular ejection fraction (LVEF) <50% or below the lowest normal threshold, as determined by ECG or heart failure (NYHA grade III or IV)
•Impossibility to measure the QT interval on ECG
•Complete left bundle branch block
•Congenital long QT syndrome of known familial antecedents of long QT syndrome
•Antecedents or current ventricular or atrial tachyarrhythmia, clinically significant
•Baseline bradycardia (<50 bpm) clinically significant
•Corrected QT interval (QTc)> 450 msec established on the mean of 3 baseline ECG
•Antecedents of myocardial infarct in the past 6 months
•Instable angor within the past 12 months
•Any heart condition clinically significant (i.e. congestive heart failure, uncontrolled hypertension)
•Active uncontrolled infection, any other concurrent disease deemed to interfere with the conduct of the study as judged by the investigator
•Severe evolving infection, or known HIV or Human T-Lymphotropic Virus type I (HTLV1) seropositivity, or active infection by hepatitis B or C virus
•Pregnant (beta-HCG) or nursing woman
•Women of childbearing potential not willing to use an effective form of contraception during participation in the study and at least three months thereafter. Patient not willing to ensure not to beget a child during participation in the study and at least three months thereafter.
•Having received an investigational treatment or participation in another trial within 30 days prior to entering this study.
•Not able to bear with the procedures or the frequency of visits planned in the trial.
•Unable to consent, under tutelage or curators, or judiciary safeguard