Overview

This trial is active, not recruiting.

Condition philadelphia chromsome positive acute lymphoblastic leukemia
Treatment nilotinib
Phase phase 2
Targets BCR-ABL, KIT, PDGF
Sponsor Johann Wolfgang Goethe University Hospitals
Start date January 2012
End date July 2017
Trial size 79 participants
Trial identifier NCT01528085, 2010-022855-46, EWALL-PH-02

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment

Primary Outcomes

Measure
Evaluation of efficacy of a nilotinib-based induction and consolidation therapy
time frame: after 12 months

Secondary Outcomes

Measure
complete haematological remission
time frame: after induction treatment (week 5)
major molecular response in bone marrow
time frame:
complete molecular response
time frame:
undetectable BCR-ABL level
time frame:
Event free survival
time frame:
Relapse free survival
time frame:
Progression free survival
time frame:
T315I or p-loop Mutations
time frame:
molecular relapse or progression
time frame:
Overall survival
time frame:
Tolerability
time frame:
Death during induction
time frame: End of induction (week 5)
Death in complete remission
time frame:

Eligibility Criteria

Male or female participants at least 55 years old.

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.

Additional Information

Official title 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)
Principal investigator Heike Pfeifer, Dr.med.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Johann Wolfgang Goethe University Hospitals.