An open label, single arm, phase II study of nilotinib 300 mg BID in newly diagnosedCP-CML patients, in order to verify disappearance of CD34+/lin-Ph+ cells from bone marrowduring treatment.

• Conditions: newly diagnosed CP-CML patients; MedDRA version: 14.1Level: LLTClassification code 10052065Term: Chronic phase chronic myeloid leukaemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-005062-34-IT
• Lead Sponsor: AZIENDA OSPEDALIERA OSPEDALE NIGUARDA CA' GRANDA (A.O. DI RILIEVO NAZIONALE)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12-21
• Last Update Posted: 10 June 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1. Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of Ph chromosome [(9;22) translocation] within 3 months of diagnosis; 2. Patients Ph negative or with variant translocations by standard cytogenetic analysis but Ph positive by FISH, are eligible as well; 3. Age = 18 years old (no upper age limit given); 4. WHO performance status =2; 5. Normal serum levels = LLN (lower limit of normal) of potassium, magnesium, total calcium corrected for serum albumin or phosphorus, or correctable to within normal limits with supplements, prior to the first dose of study medication; 6. AST and ALT = 2.5 x ULN or = 5.0 x ULN if considered due to leukaemia; 7. Alkaline phosphatase = 2.5 x ULN unless considered due to leukaemia; 8. Total bilirubin = 1.5 x ULN, except know Mb Gilbert; 9. Serum lipase and amylase = 1.5 x ULN; 10. Serum creatinine = 1.5 x ULN; 11.Written informed consent signed prior to any study procedures being performed.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 87
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 87

Exclusion Criteria

1. Pre-treatment with hydroxyurea for > 3 months and with imatinib is not permitted; 2. Prior accelerated phase including clonal evolution or blast crisis; 3. Contraindication to excipients in study medication; 4. Known impaired cardiac function including any of the following: a. LVEF < 45% b. Complete left bundle branch block c. Right bundle branch block plus left anterior hemiblock, bifascicular block d. Use of a ventricular-paced pacemaker e. Congenital long QT syndrome f. History or presence of clinically significant ventricular or atrial tachyarrhythmias g. Clinically significant resting bradycardia (< 50 beats per minute) h. QTcF > 450 msec on screening ECG. If QTcF > 450 msec and electrolytes are not within normal ranges before nilotinib dosing, electrolytes should be corrected and then the patient rescreened for QTcF criterion i. Myocardial infarction within 12 months prior to starting nilotinib j. Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension); 5. History of acute (i.e. within 1 year of starting study medication) or chronic pancreatitis; 6. 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; 7. 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); 8. Concomitant medications with potential QT prolongation (see link for complete list: http://www.torsades.org/medical-pros/drug-lists/printable-drug-list.cfm); 9. Concomitant medications known to be strong inducers or inhibitors of the CYP450 Isoenzyme CYP3A4:see link for complete list (http://medicine.iupui.edu/flockhart/table.htm); 10. Patients who have undergone major surgery = 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy; 11. 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 14 days prior to administration of nilotinib. Post menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential. Female patients must agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following discontinuation of study drug; 12. Treatment with any haematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF) = 1 week prior to starting study drug; 13. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory); 14. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention; 15. Patients unwilling or unable to comply with the protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified