chronic phase CML MedDRA version: 21.0 Level: LLT Classification code 10009700 Term: CML System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tasigna
Product Name: Nilotinib
Product Code: AMN107
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Concentration unit: mg milligram(s)
Concentra
Sponsors
Friedrich-Schiller-Universität Jena
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of Ph chromosome [t(9;22)(q34;q11)]. • Ph negative cases or patients with variant translocations who are BCR-ABL positive in multiplex PCR (Cross, et al 1994) are eligible as well. • Pretreatment with hydroxyurea for 6 months and imatinib or nilotinib for a duration of up to 6 weeks is permitted. • Age = 18 years old (no upper age limit given) • 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. • ASAT and ALAT = 2.5 x ULN (upper limit of normal) or = 5.0 x ULN if considered due to leukemia • Alkaline phosphatase = 2.5 x ULN unless considered due to leukemia • Total bilirubin = 1.5 x ULN, except known Mb. Gilbert • Serum lipase and amylase = 1.5 x ULN • Serum creatinine = 2 x ULN • Written informed consent prior to any study procedures being performed. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 245 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 475
Exclusion criteria
Exclusion criteria: • Known impaired cardiac function, including any of the following: - Left ventricular ejection fraction (LVEF) 450 msec on screening ECG. If QTc > 450 ms 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 therapy. • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure, uncontrolled hypertension) • History of acute (i.e., within 1 year of starting study medication) or chronic pancreatitis • Acute or chronic viral hepatitis with moderate or severe hepatic impairment (Child-Pugh scores >6), even if controlled. • 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 be strong inducers or inhibitors of the CYP450 isoenzyme CYP3A4: see link for complete list (http://medicine.iupui.edu/flockhart/table.htm) • 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 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 • Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory) • Active autoimmune disorder, including autoimmune hepatitis • Known serious hypersensitivity reactions to peginterferon alfa-2b or interferon alfa-2b or drug excipients • Known serious hypersensitivity reactions to 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Co-primary objectives are: 1. To evaluate the rate of MMR at 18 months of nilotinib 300 mg BID monotherapy vs. nilotinib 300 mg BID + pegylated interferon alpha (Peginterferon alpha-2b) 2. To evaluate the rate of continuous MMR after discontinuation of nilotinib vs. interferon alpha.;Secondary Objective: To evaluate 1. Rate of CCyR and MMR by 12, 18 and 24 months 2. Time to CCyR, MMR, MR4 and MR4.5 3. Rate of MR4 and MR4.5 during maintenance therapy and after discontinuation 4. Progression-Free Survival and Overall Survival at 12, 24, and 60 months of treatment 5. Rate of patients off treatment for at least 6 months at 60 months after start of treatment: all patients and comparison of treatment arms 6. Safety and tolerability profile of nilotinib in comparison with nilotinib + IFN and IFN 7. Patients compliance to nilotinib based therapies 8. Quality of life during induction therapy with nilotinib vs. nilotinib + IFN and during maintenance therapy with nilotinib vs. IFN. 9. Pharmacoeconomics of the treatment strategies.;Primary end point(s): 1. rate of MMR;;Timepoint(s) of evaluation of this end point: 1. at 18 months and continuously after dicontinuation of trial drugs; | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Rate of CCyR and MMR 2. time to CCyR, MMR, M4 and M4.5 3. rate of MR4 and MR4.5 4. progression free survival 5. overall survival 6. Rate of patients off treatment for at least 6 months 7. safety and tolerability of nilotinib compared with nilotinib+IFN and IFN 8. patients compliance to nilotinib based therapies 9. quality of life 10. pharmacoeconimics of treatment strategies;Timepoint(s) of evaluation of this end point: 1. 12, 18 and 24 months 2. during trial 3. during maintenance and after discontinuation 4. 12, 24 and 60 months 5. 12, 24 and 60 months 6. 60 months after start of treatment 7. end of trial 8. end of trial 9. during induction and maintanence therapy 10. end of trial | — |
Countries
Czech Republic, Germany
Contacts
Public ContactCML V Information
Universitätsklinikum Jena
Outcome results
None listed