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)

Goethe University69 sites in 2 countries79 target enrollmentJanuary 2012

ConditionsPhiladelphia Chromsome Positive Acute Lymphoblastic Leukemia

DrugsNilotinib

Overview

Phase: Phase 2
Intervention: Not specified
Conditions: Philadelphia Chromsome Positive Acute Lymphoblastic Leukemia
Sponsor: Goethe University
Enrollment: 79
Locations: 69
Primary Endpoint: Evaluation of efficacy of a nilotinib-based induction and consolidation therapy
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

January 2012

End Date

March 10, 2020

Last Updated

5 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Goethe University

Responsible Party

Principal Investigator

Heike Pfeifer MD

Dr.med.

Goethe University

Eligibility Criteria

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.