newly diagnosed CP-CML patients MedDRA version: 14.1 Level: LLT Classification code 10052065 Term: Chronic phase chronic myeloid leukaemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: TASIGNA*112CPS 150MG
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration n
Sponsors
AZIENDA OSPEDALIERA OSPEDALE NIGUARDA CA' GRANDA (A.O. DI RILIEVO NAZIONALE)
Eligibility
Sex/Gender
All
Inclusion criteria
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
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To verify the disappearance of BM CD34+/lin- Ph+ cells at the end of 6 months of treatment using cell selection system and FISH in patients showing a CCyR.;Secondary Objective: To estimate CCyR at 3, 6 and 12 months; to estimate the percentage of patients with MR = 10% IS at 3 months in the peripheral blood (PB); to estimate the percentage of patients with MR = 1% IS at 6 months in the PB; to estimate MMR IS by 3, 6 and 12 month periods in the PB; to estimate MR4,5 IS by 3, 6 and 12 month periods in the PB; to estimate the disappearance of CD34+/lin- Ph+ cells in the BM at the end of 3 and 12 months of treatment using cell selection system and FISH.;Primary end point(s): The primary efficacy endpoint is to measure the rate of CD34+/lin-Ph+ cells in the BM after 6 months of treatment. In order to obtain this result, BM blood of all enrolled patients (see Appendix 1) will be stored after 6 months of treatment with nilotinib. The isolated CD34+/lin- cells will be employed for standard FISH analysis. These endpoints will be obtained at the central laboratory of Niguarda Ca’ Granda Hospital, Milano, Italy.;Timepoint(s) of evaluation of this end point: six months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will be reached performing: - the same analyzes on CD34+/lin- cells at diagnosis, at 3 and 12 months of treatment; - cytogenetic analysis to estimate the rate of CCyR at 3, 6 and 12 months; this analysis will be performed at each local laboratory; - molecular analysis to determinate the rate of MR (= 10%, = 1%, MMR, MR4,5 IS) at 3, 6 and 12 months in the peripheral blood; the molecular analysis will be performed using the Labnet standardized laboratories in Lombardia.;Timepoint(s) of evaluation of this end point: three,six, twelve, twenty-four months | — |
Countries
Italy
Contacts
Public Contactester.pungolino@ospedaleniguarda.it
SC EMATOLOGIA
Outcome results
None listed