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Evaluation of Efficacy and Safety of Nilotinib in Combination With Chemotherapy in Elderly Patients With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

2020年7月29日 更新者：Heike Pfeifer MD、Goethe University

An Open Label Phase II Study to Evaluate the Efficacy and Safety of Induction and Consolidation Therapy With Nilotinib in Combination With Chemotherapy in Patients Aged 55 Years and Over With Philadelphia Chromosome Positive (Ph+ or BCR-ABL+) Acute Lymphoblastic Leukemia (ALL)

The goal of this trial is to evaluate the efficacy and the tolerance of the combination of nilotinib with chemotherapy in the front-line setting as induction and consolidation therapy in Ph+ ALL patient aged 55 years and over. A European consensus has been reached to adopt a common chemotherapeutic schedule for patients aged 55 years and over. This schedule will be used in this trial with the addition of nilotinib as concomitant therapy during induction, consolidation and maintenance. The patients will be prospectively monitored for minimal residual disease and bcr-abl tyrosine kinase domain mutations.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

79

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 德国
      • Aachen、德国、52074
        • Uniklinik Aachen
      • Berlin、德国、13353
        • Charité Universitätsmedizin Berlin
      • Düsseldorf、德国、40225
        • University Hospital Düsseldorf
      • Göttingen、德国、37075
        • Universitätsklinikum Göttingen
      • Hamburg、德国、20099
        • Asklepios Klinik St. Georg
      • Kiel、德国、24116
        • Universitätsklinikum Schleswig-Holstein Campus Kiel
      • Leipzig、德国、04103
        • Universität Leipzig, José-Carreras-Haus
      • Mainz、德国、55101
        • Universitätskliniken Mainz
      • Mannheim、德国、68167
        • Klinikum Mannheim
      • München、德国、81377
        • Universitätsklinikum Großhadern
      • Nürnberg、德国、90419
        • Klinikum Nürnberg Nord
      • Oldenburg、德国、26133
        • Klinikum Oldenburg
      • Rostock、德国、18055
        • Universität Rostock
      • Ulm、德国、89070
        • Medizinische Universitätsklinik Ulm
      • Würzburg、德国、97080
        • Universität Würzburg
    • Baden-Württemberg
      • Stuttgart、Baden-Württemberg、德国、70376
        • Robert Bosch Krankenhaus
    • Bayern
      • Regensburg、Bayern、德国、93042
        • Klinikum der Universität Regensburg
    • Hessen
      • Frankfurt、Hessen、德国、60590
        • University Hospital of Frankfurt, Medical Dept. II
    • NRW
      • Essen、NRW、德国、45147
        • Universitätsklinikum Essen
      • Münster、NRW、德国、48149
        • Universitätsklinik Münster
    • Niedersachsen
      • Hannover、Niedersachsen、德国、30625
        • Medizinische Hochschule Hannover
    • Sachsen
      • Dresden、Sachsen、德国、01307
        • Universitatsklinik Dresden
  • 法国
      • AMIENS Cedex 1、法国、80054
        • CHU d'Amiens - Hôpital Sud
      • ANGERS Cedex 09、法国、49933
        • CHU Angers
      • Aix-en-Provence cedex 1、法国、13616
        • Centre Hospitalier du Pays d'Aix
      • Argenteuil Cedex、法国、95107
        • Centre Hospitalier Victor Dupouy
      • BESANÇON Cedex、法国、25030
        • CHU de Besançon - Hôpital Jean Minjoz
      • BREST Cedex、法国、29609
        • Chu de Brest - Hopital Morvan
      • Bayonne、法国、64100
        • Centre Hospitalier de la Côte Basque
      • Caen、法国、14000
        • "CHU Cote de nacre "
      • Clermont Ferrand、法国、63003
        • CHU Estaing
      • Creteil、法国、94010
        • AP-HP - Hôpital Henri Mondor
      • DIJON Cedex、法国、21079
        • CHRU de Dijon
      • Grenoble cedex 9、法国、38043
        • CHU de GRENOBLE
      • LE CHESNAY Cedex、法国、78157
        • Ch de Versailles - Hopital Andre Mignot
      • LILLE Cedex、法国、59037
        • CHRU de Lille
      • LIMOGES Cedex、法国、87042
        • C H U de Limoges - Hôpital Dupuytren
      • Lille Cedex、法国、59020
        • Groupe Hospitalier de l'Institut Catholique de Lille, hôpital Saint-Vincent
      • MEAUX Cedex、法国、77104
        • CH de Meaux
      • MONTPELLIER Cedex 5、法国、34295
        • Hôpital Saint-Eloi
      • MULHOUSE Cedex、法国、68070
        • CH de Mulhouse - Hôpital Emile Muller
      • Marseille cedex 9、法国、13273
        • Institut Paoli-Calmettes
      • Nantes、法国、44000
        • CHU Hôtel Dieu, Nantes
      • Nice、法国、06200
        • Chu de Nice - Hôpital L'Archet 1
      • ORLEANS Cedex、法国、45032
        • CHR d'Orléans - hôpital La Source
      • PARIS Cedex 10、法国、75010
        • AP-HP - Hôpital Saint Louis
      • PARIS Cedex 15、法国、75743
        • AP-HP - Hôpital Necker
      • PARIS cedex 12、法国、75571
        • AP-HP - hôpital Saint-Antoine
      • PERPIGNAN cedex 09、法国、66046
        • CH de Perpignan - Hôpital Saint-Jean
      • PESSAC Cedex、法国、33604
        • CHU de Bordeaux - Hôpital Haut-Lévêque
      • POITIERS Cedex、法国、86021
        • CHU de Poitiers - Hôpital la Milétrie
      • Pierre-Bénite Cedex、法国、69495
        • Centre Hospitalier LYON SUD
      • Pringy Cedex、法国、74374
        • CH de la Region d'Annecy
      • REIMS Cedex、法国、51092
        • CHU de Reims - Hôpital Robert Debré
      • RENNES Cedex 9、法国、35033
        • CHU de Rennes, Hopital Pontchaillou
      • Rouen Cedex 1、法国、76038
        • Centre Henri Becquerel, ROUEN
      • SAINT DENIS Cedex、法国、97405
        • CHU de la Réunion - Hôpital Felix Guyon
      • STRASBOURG Cedex、法国、67098
        • CHRU de Strasbourg - Hôpital Hautepierre
      • TOULON Cedex 9、法国、83041
        • Hia Sainte Anne
      • TOURS Cedex 9、法国、37044
        • CHRU de Tours - Hopital Bretonneau
      • Toulouse、法国、31100
        • "Institut Universitaire du Cancer (CHU de Toulouse - Hôpital Purpan)"
      • VALENCIENNES Cedex、法国、59322
        • Centre Hospitalier de Valenciennes
      • Vandoeuvre Les Nancy、法国、54511
        • CHU de Nancy - Hôpital Brabois
  • 西班牙
      • Barcelona、西班牙、08036
        • Hospital Clinic de Barcelona
      • Barcelona、西班牙、08916
        • Hospital Universitario Germans Trias i Pujol (ICO - Badalona)
      • Madrid、西班牙、28041
        • Hospital Universitario 12 De Octubre (Madrid)
      • Salamanca、西班牙、37007
        • Hospital Clinico Universitario de Salamanca
      • Sevilla、西班牙、41013
        • Hospital Universitario Virgen del Rocío (Sevilla)
      • Valencia、西班牙、46026
        • Hospital Universitario y Politécnico La Fe (Valencia)

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

55年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  1. Male or female patients > 55 years
  2. Philadelphia chromosome- or BCR-ABL positive acute lymphoblastic leukemia
  3. Not previously treated except with corticosteroids or single dose vincristine (three doses cyclophosphamide accepted)
  4. With or without documented CNS involvement
  5. WHO performance status < 2
  6. Normal serum levels > LLN (lower limit of normal) of potassium, magnesium, total calcium corrected for serum albumin; or corrected to within normal limits with supplements, prior to the first dose of study medication
  7. Signed written inform consent
  8. Molecular evaluation for BCR-ABL performed
  9. Willingness of male subjects whose sexual partners are women of child-bearing potential (WOCBP), to use an effective form of contraception (pearl index < 1%), such as complete sexual abstinence, combined oral contraceptive, hormone IUCD, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant or depot contraceptive injection in combination with a second method of contraception like a condom or a cervical cap / diaphragm with spermicide or surgical sterilisation (vasectomy) in male patients during the study and at least 6 months thereafter. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or surgical sterilization or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months).

Exclusion Criteria:

  1. Patient previously treated with tyrosine kinase inhibitors

  2. Known impaired cardiac function, including any of the following:

    • LVEF < 45%
    • Complete left bundle branch block
    • Right bundle branch block plus left anterior hemiblock, bifascicular block
    • Use of a ventricular-paced pacemaker
    • Congenital long QT syndrome
    • History of or presence of clinically significant ventricular or atrial tachyarrhythmias
    • Clinically significant resting bradycardia (< 50 beats per minute)
    • QTcF>450 msec on screening ECG. If QTc > 450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion.
    • Myocardial infarction with 12 months prior to starting nilotinib
    • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)
  3. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
  4. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or known infection with Hepatitis B or C
  5. Treatment with any, other investigational agent or participating in another trial within 30 days prior to entering this study
  6. Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal or > 5 times ULN if considered due to leukemia
  7. Total bilirubin > 2 fold the institutional upper limit unless considered to be due to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht
  8. Concurrent severe diseases which exclude the administration of therapy
  9. Past history of acute or chronic pancreatits

  10. Patients unwilling or unable to comply with the protocol.e branch block; Right bundle branch block plus left anterior hemiblock, bifascicular block; Use of a ventricular-paced pacemaker; congenital long QT syndrome

    • History of or presence of clinically significant ventricular or atrial tachyarrhythmias
    • Clinically significant resting bradycardia (< 50 beats per minute)
    • QTcF>450 msec on screening ECG. If QTc > 450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion.
    • Myocardial infarction with 12 months prior to starting nilotinib

    • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)

      • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
      • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) or known infection with Hepatitis B or C
      • Treatment with any, other investigational agent or participating in another trial within 30 days prior to entering this study
      • Inadequate hepatic functions defined as ASAT or ALAT > 2,5 times the institutional upper limit of normal or > 5 times ULN if considered due to leukemia
      • Total bilirubin > 2 fold the institutional upper limit unless considered to be due to organ involvement by the leukemia or to M. Gilbert / M. Meulengracht
      • Concurrent severe diseases which exclude the administration of therapy
      • Past history of acute or chronic pancreatits
      • Patients unwilling or unable to comply with the protocol.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：不适用
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Evaluation of efficacy of a nilotinib-based induction and consolidation therapy
大体时间：after 12 months
rate of patients without event
after 12 months

次要结果测量

结果测量
措施说明
大体时间
总生存期
无进展生存期
无事件生存
无复发生存期
complete haematological remission
大体时间：after induction treatment (week 5)
The rate of complete haematological remission after induction treatment
after induction treatment (week 5)
major molecular response in bone marrow
major molecular response defined by a BCR-ABL/ABL < 0.1% in bone marrow
complete molecular response
complete molecular response defined by a BCR-ABL/ABL < 0.001% in bone marrow
undetectable BCR-ABL level
The proportion of patients with confirmed undetectable BCR-ABL level with a test sensitivity of at least 4.5 log.
T315I or p-loop Mutations
Detection of a T315I or p-loop BCR-ABL TK domain mutation
molecular relapse or progression
The proportion of patients with molecular relapse or progression
Tolerability
Tolerability as determined by descriptive assessment of adverse events and discontinuation due to treatment-related SAEs
Death during induction
大体时间：End of induction (week 5)
(all patients who started treatment)
End of induction (week 5)
Death in complete remission

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Goethe University

调查人员

  • 首席研究员：Heike Pfeifer, Dr.med.、Johann Wolfgang Goethe University Hospital

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2012年1月1日

初级完成 (实际的)

2020年3月10日

研究完成 (实际的)

2020年3月10日

研究注册日期

首次提交

2012年2月3日

首先提交符合 QC 标准的

2012年2月3日

首次发布 (估计)

2012年2月7日

研究记录更新

最后更新发布 (实际的)

2020年7月30日

上次提交的符合 QC 标准的更新

2020年7月29日

最后验证

2020年7月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • EWALL-PH-02
  • 2010-022855-46 (EudraCT编号)

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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