Evaluation of Efficacy and Safety of Nilotinib in Combination With Chemotherapy in Elderly Patients With Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia
- Conditions
- Philadelphia Chromsome Positive Acute Lymphoblastic Leukemia
- Registration Number
- NCT01528085
- Lead Sponsor
- Goethe University
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 79
- 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).
-
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.
-
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Evaluation of efficacy of a nilotinib-based induction and consolidation therapy after 12 months rate of patients without event
- Secondary Outcome Measures
Name Time Method Event free survival Overall survival complete haematological remission after induction treatment (week 5) The rate of complete haematological remission after induction treatment
Relapse free survival 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 End of induction (week 5) (all patients who started treatment)
Death in complete remission 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.
Progression free survival T315I or p-loop Mutations Detection of a T315I or p-loop BCR-ABL TK domain mutation
Trial Locations
- Locations (69)
CHU de La Réunion - Hôpital Félix Guyon
🇫🇷SAINT DENIS Cedex, France
CHRU de Strasbourg - Hôpital Hautepierre
🇫🇷STRASBOURG Cedex, France
HIA Sainte Anne
🇫🇷TOULON Cedex 9, France
Centre Hospitalier du Pays d'Aix
🇫🇷Aix-en-Provence cedex 1, France
CHU d'Amiens - Hôpital Sud
🇫🇷AMIENS Cedex 1, France
CHU de Brest - Hôpital Morvan
🇫🇷BREST Cedex, France
Chu Angers
🇫🇷ANGERS Cedex 09, France
Centre Hospitalier Victor Dupouy
🇫🇷Argenteuil Cedex, France
Centre Hospitalier de la Côte Basque
🇫🇷Bayonne, France
CHU de Besançon - Hôpital Jean Minjoz
🇫🇷BESANÇON Cedex, France
CHU Estaing
🇫🇷Clermont Ferrand, France
"CHU Cote de nacre "
🇫🇷Caen, France
AP-HP - Hôpital Henri Mondor
🇫🇷Creteil, France
CHU de Grenoble
🇫🇷Grenoble cedex 9, France
CHRU de Dijon
🇫🇷DIJON Cedex, France
CH de Versailles - Hôpital André Mignot
🇫🇷LE CHESNAY Cedex, France
Groupe Hospitalier de l'Institut Catholique de Lille, hôpital Saint-Vincent
🇫🇷Lille Cedex, France
CHRU de Lille
🇫🇷LILLE Cedex, France
Institut Paoli-Calmettes
🇫🇷Marseille cedex 9, France
CH de Meaux
🇫🇷MEAUX Cedex, France
CH de Mulhouse - Hôpital Emile Muller
🇫🇷MULHOUSE Cedex, France
Hôpital Saint-Eloi
🇫🇷MONTPELLIER Cedex 5, France
CHU de Nice - Hôpital l'Archet 1
🇫🇷Nice, France
CHU Hôtel Dieu, Nantes
🇫🇷Nantes, France
CHR d'Orléans - Hôpital La Source
🇫🇷ORLEANS Cedex, France
AP-HP - Hôpital SAINT-ANTOINE
🇫🇷PARIS cedex 12, France
AP-HP - Hôpital Saint Louis
🇫🇷PARIS Cedex 10, France
CH de Perpignan - Hôpital Saint-Jean
🇫🇷PERPIGNAN cedex 09, France
AP-HP - Hôpital Necker
🇫🇷PARIS Cedex 15, France
CHU de Bordeaux - Hôpital Haut-Lévêque
🇫🇷PESSAC Cedex, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Bénite Cedex, France
CH de la Région d'Annecy
🇫🇷Pringy Cedex, France
CHU de Reims - Hôpital Robert Debré
🇫🇷REIMS Cedex, France
CHU de Poitiers - Hôpital La Milétrie
🇫🇷POITIERS Cedex, France
CHU de Rennes, Hôpital Pontchaillou
🇫🇷RENNES Cedex 9, France
Centre Henri Becquerel, Rouen
🇫🇷Rouen Cedex 1, France
CHRU de Tours - Hôpital Bretonneau
🇫🇷TOURS Cedex 9, France
"Institut Universitaire du Cancer (CHU de Toulouse - Hôpital Purpan)"
🇫🇷Toulouse, France
CHU de Nancy - Hôpital Brabois
🇫🇷Vandoeuvre Les Nancy, France
Centre Hospitalier de Valenciennes
🇫🇷VALENCIENNES Cedex, France
Klinikum der Universität Regensburg
🇩🇪Regensburg, Bayern, Germany
Universitätsklinik Münster
🇩🇪Münster, NRW, Germany
University Hospital of Frankfurt, Medical Dept. II
🇩🇪Frankfurt, Hessen, Germany
Medizinische Hochschule Hannover
🇩🇪Hannover, Niedersachsen, Germany
Universitätsklinikum Essen
🇩🇪Essen, NRW, Germany
Uniklinik Aachen
🇩🇪Aachen, Germany
Universitätsklinik Dresden
🇩🇪Dresden, Sachsen, Germany
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
University Hospital Düsseldorf
🇩🇪Düsseldorf, Germany
Asklepios Klinik St. Georg
🇩🇪Hamburg, Germany
Universität Leipzig, José-Carreras-Haus
🇩🇪Leipzig, Germany
Universitätsklinikum Schleswig-Holstein Campus Kiel
🇩🇪Kiel, Germany
Universitätskliniken Mainz
🇩🇪Mainz, Germany
Klinikum Mannheim
🇩🇪Mannheim, Germany
Universität Rostock
🇩🇪Rostock, Germany
Universitätsklinikum Großhadern
🇩🇪München, Germany
Klinikum Oldenburg
🇩🇪Oldenburg, Germany
Klinikum Nürnberg Nord
🇩🇪Nürnberg, Germany
Medizinische Universitätsklinik Ulm
🇩🇪Ulm, Germany
Universität Würzburg
🇩🇪Würzburg, Germany
Hospital Universitario Germans Trias i Pujol (ICO - Badalona)
🇪🇸Barcelona, Spain
Hospital Clínic de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre (Madrid)
🇪🇸Madrid, Spain
Hospital Clínico Universitario de Salamanca
🇪🇸Salamanca, Spain
Hospital Universitario y Politécnico La Fe (Valencia)
🇪🇸Valencia, Spain
Hospital Universitario Virgen del Rocío (Sevilla)
🇪🇸Sevilla, Spain
C H U de Limoges - Hôpital Dupuytren
🇫🇷LIMOGES Cedex, France
Universitätsklinikum Göttingen
🇩🇪Göttingen, Germany
Robert Bosch Krankenhaus
🇩🇪Stuttgart, Baden-Württemberg, Germany