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

NCT ID: NCT01528085

Last Updated: 2020-07-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 79 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2020-03-10

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.

Conditions

Philadelphia Chromsome Positive Acute Lymphoblastic Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

Nilotinib

Nilotinib, p.o Chemotherapy (Dexamethasone, Methotroxate, Cyclophosphamide (optional), Vincristine, Vindesine, Cytarabine, 6-Mercapto-Purine)

Intervention Type: DRUG

Other Intervention Names

Tasigna

Eligibility Criteria

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.

• Minimum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Goethe University

OTHER

Sponsor Role: lead

Responsible Party

Heike Pfeifer MD

Dr.med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Heike Pfeifer, Dr.med.

Role: PRINCIPAL_INVESTIGATOR

Johann Wolfgang Goethe University Hospital

Locations

Centre Hospitalier du Pays d'Aix

Aix-en-Provence, , France

CHU d'Amiens - Hôpital Sud

Amiens, , France

Chu Angers

Angers, , France

Centre Hospitalier Victor Dupouy

Argenteuil, , France

Centre Hospitalier de la Côte Basque

Bayonne, , France

CHU de Besançon - Hôpital Jean Minjoz

Besançon, , France

CHU de Brest - Hôpital Morvan

Brest, , France

"CHU Cote de nacre "

Caen, , France

CHU Estaing

Clermont-Ferrand, , France

AP-HP - Hôpital Henri Mondor

Créteil, , France

CHRU de Dijon

Dijon, , France

CHU de Grenoble

Grenoble, , France

CH de Versailles - Hôpital André Mignot

Le Chesnay, , France

Groupe Hospitalier de l'Institut Catholique de Lille, hôpital Saint-Vincent

Lille, , France

CHRU de Lille

Lille, , France

C H U de Limoges - Hôpital Dupuytren

Limoges, , France

Institut Paoli-Calmettes

Marseille, , France

CH de Meaux

Meaux, , France

Hôpital Saint-Eloi

Montpellier, , France

CH de Mulhouse - Hôpital Emile Muller

Mulhouse, , France

CHU Hôtel Dieu, Nantes

Nantes, , France

CHU de Nice - Hôpital l'Archet 1

Nice, , France

CHR d'Orléans - Hôpital La Source

Orléans, , France

AP-HP - Hôpital Saint Louis

Paris, , France

AP-HP - Hôpital SAINT-ANTOINE

Paris, , France

AP-HP - Hôpital Necker

Paris, , France

CH de Perpignan - Hôpital Saint-Jean

Perpignan, , France

CHU de Bordeaux - Hôpital Haut-Lévêque

Pessac, , France

Centre Hospitalier Lyon Sud

Pierre-Bénite, , France

CHU de Poitiers - Hôpital La Milétrie

Poitiers, , France

CH de la Région d'Annecy

Pringy, , France

CHU de Reims - Hôpital Robert Debré

Reims, , France

CHU de Rennes, Hôpital Pontchaillou

Rennes, , France

Centre Henri Becquerel, Rouen

Rouen, , France

CHU de La Réunion - Hôpital Félix Guyon

Saint-Denis, , France

CHRU de Strasbourg - Hôpital Hautepierre

Strasbourg, , France

HIA Sainte Anne

Toulon, , France

"Institut Universitaire du Cancer (CHU de Toulouse - Hôpital Purpan)"

Toulouse, , France

CHRU de Tours - Hôpital Bretonneau

Tours, , France

Centre Hospitalier de Valenciennes

Valenciennes, , France

CHU de Nancy - Hôpital Brabois

Vandœuvre-lès-Nancy, , France

Robert Bosch Krankenhaus

Stuttgart, Baden-Wurttemberg, Germany

Klinikum der Universität Regensburg

Regensburg, Bavaria, Germany

University Hospital of Frankfurt, Medical Dept. II

Frankfurt am Main, Hesse, Germany

Medizinische Hochschule Hannover

Hanover, Lower Saxony, Germany

Universitätsklinikum Essen

Essen, North Rhine-Westphalia, Germany

Universitätsklinik Münster

Münster, North Rhine-Westphalia, Germany

Universitätsklinik Dresden

Dresden, Saxony, Germany

Uniklinik Aachen

Aachen, , Germany

Charité Universitätsmedizin Berlin

Berlin, , Germany

University Hospital Düsseldorf

Düsseldorf, , Germany

Universitätsklinikum Göttingen

Göttingen, , Germany

Asklepios Klinik St. Georg

Hamburg, , Germany

Universitätsklinikum Schleswig-Holstein Campus Kiel

Kiel, , Germany

Universität Leipzig, José-Carreras-Haus

Leipzig, , Germany

Universitätskliniken Mainz

Mainz, , Germany

Klinikum Mannheim

Mannheim, , Germany

Universitätsklinikum Großhadern

München, , Germany

Klinikum Nürnberg Nord

Nuremberg, , Germany

Klinikum Oldenburg

Oldenburg, , Germany

Universität Rostock

Rostock, , Germany

Medizinische Universitätsklinik Ulm

Ulm, , Germany

Universität Würzburg

Würzburg, , Germany

Hospital Clínic de Barcelona

Barcelona, , Spain

Hospital Universitario Germans Trias i Pujol (ICO - Badalona)

Barcelona, , Spain

Hospital Universitario 12 de Octubre (Madrid)

Madrid, , Spain

Hospital Clínico Universitario de Salamanca

Salamanca, , Spain

Hospital Universitario Virgen del Rocío (Sevilla)

Seville, , Spain

Hospital Universitario y Politécnico La Fe (Valencia)

Valencia, , Spain

Countries

France; Germany; Spain

Related Links

https://www.uct-frankfurt.de/fuer-aerzte/klinische-studien.html

Trial register of University Cancer Center Frankfurt, additional trial information

Other Identifiers

2010-022855-46

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EWALL-PH-02

Identifier Type: -

Identifier Source: org_study_id