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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

2020년 7월 29일 업데이트: 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.

연구 개요

상태

완전한

정황

Philadelphia Chromsome Positive Acute Lymphoblastic Leukemia

개입 / 치료

의약품: Nilotinib

연구 유형

중재적

등록 (실제)

단계

2 단계

연락처 및 위치

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연구 장소

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

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

55년 이상 (성인, 고령자)

건강한 자원 봉사자를 받아들입니다

아니

연구 대상 성별

모두

설명

Inclusion Criteria:

Male or female patients > 55 years
Philadelphia chromosome- or BCR-ABL positive acute lymphoblastic leukemia
Not previously treated except with corticosteroids or single dose vincristine (three doses cyclophosphamide accepted)
With or without documented CNS involvement
WHO performance status < 2
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
Signed written inform consent
Molecular evaluation for BCR-ABL performed
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:

Patient previously treated with tyrosine kinase inhibitors
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)
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.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.

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

주 목적: 치료
할당: 해당 없음
중재 모델: 단일 그룹 할당
마스킹: 없음(오픈 라벨)

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정	측정값 설명	기간
Evaluation of efficacy of a nilotinib-based induction and consolidation therapy 기간: after 12 months	rate of patients without event	after 12 months

2차 결과 측정

결과 측정	측정값 설명	기간
전반적인 생존
무진행 생존
이벤트 프리 서바이벌
재발 없는 생존
complete haematological remission 기간: 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 기간: End of induction (week 5)	(all patients who started treatment)	End of induction (week 5)
Death in complete remission

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Goethe University

수사관

수석 연구원: Heike Pfeifer, Dr.med., Johann Wolfgang Goethe University Hospital

간행물 및 유용한 링크

연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.

유용한 링크

Trial register of University Cancer Center Frankfurt, additional trial information

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작

2012년 1월 1일

기본 완료 (실제)

2020년 3월 10일

연구 완료 (실제)

2020년 3월 10일

연구 등록 날짜

최초 제출

2012년 2월 3일

QC 기준을 충족하는 최초 제출