Nilotinib in PH+, BCR-, ABL+ CML Patients

• Status: Completed
• Trial end date: 2018-04-27
• Target enrollment: 0
• Participant gender: All

Summary

This study is an open-label, multicentric, phase IIIb study of NILOTINIB administered orally twice daily for 24 months and indefinitely if it is in the interest of the patient.

The primary objective of the trial is to evaluate the efficacy of nilotinib, 300 mg twice daily with dose increase to 400 mg twice daily in case of suboptimal response or failure (excluding patients who will fail for progression to ABP), in a population of patients with Ph-positive, BCR-ABL positive CML in early CP.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto

Criteria

Inclusion Criteria:

• Age ≥ 18

• Male or female patients with diagnosis of Ph+ and/or BCR-ABL+ CML

• Early chronic phase (within 6 months from diagnosis)

• Pretreatment with Hydroxyurea or Anagrelide for a duration of up to 3 months and/or pretreatment with Imatinib for up to 30 days are permitted

• Normal serum levels of potassium, magnesium, phosphorus, total calcium corrected for serum albumin or phosphorus, or correctable to within normal limits with supplements prior to the first dose of study medication

• Written informed consent prior to any study procedures being performed

• AST and ALT ≤ 2.5 x ULN or ≤ 5.0 x ULN if considered due to leukaemia

• Alkaline phosphatase ≤ 2.5 x ULN unless considered due to leukaemia

• Total direct bilirubin ≤ 1.5 x ULN, except know Mb. Gilbert

• Serum creatinine ≤ 1.5 x ULN

Exclusion Criteria:

• 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)

• QTc>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 QTc criterion.

• Myocardial infarction within 12 months prior to starting study drugs

• Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension)

• Serum lipase and amylase > 1.5 x ULN (upper limit of normal) or history of acute (i.e., within 1 year of starting study medication) or chronic pancreatitis

• Other concurrent uncontrolled medical conditions (e.g., uncontrolled diabetes, active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol

• Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery)

• Concomitant medications with potential QT prolongation (see link for complete list:

http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm)

• Concomitant medications known to interact with CYP450 isoenzymes (CYP3A4, CYP2C9,andCYP2C8:link for complete list: http://medicine.iupui.edu/flockhart/table.html..

• Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy

• Patients who are pregnant or breast feeding, or women of reproductive potential not employing an effective method of birth control. (Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to administration of nilotinib).

• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention.

• Patients unwilling or unable to comply with the protocol