chronic myeloid leukemia (CML) in 1st chronic phase and confirmed major molecular response (MMR) MedDRA version: 19.0 Level: LLT Classification code 10009700 Term: CML System Organ Class: 100000004864 MedDRA version: 19.0 Level: LLT Classification code 10066506 Term: CML progression System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tasigna
Product Name: Nilotinib
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Concentration unit: mg milligram(s)
Concentration type: equal
Conc
Sponsors
Medical Center - University of Freiburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed written informed consent 2. Male or female patients aged =18 years (without upper limit of age) 3. ECOG performance status of 0 to 2 4. CML in chronic phase, with chronic phase defined as blasts 0.0032% and =0.1% IS confirmed by central laboratory at screen-ing will be required for randomisation 7. Patients must have a serum Creatinine of = 1.5 x ULN, SGOT = 1.5 x ULN, total bilirubin = 1.5 x ULN (except known M. Gilbert), and Lipase = 1.5 x ULN 8. Women of child-bearing potential defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months, must have a negative serum pregnancy test during screening period. Male and female patients of reproductive potential must agree to employ highly effective methods of birth control throughout the study and for up to 3 months following discontinuation of study drug. Appropriate methods are e.g. a highly effective method of first choice, i.e. a method with a low failure rate (less than 1% per year) like sexual abstinence, combined oral contraceptives, implants, injectable, some Intra Uterine Devices (IUDs), vasectomized partner, in combination with a method of second choice like condom, diaphragm, or cup pessary with spermicidal foam/gel/film/cream/suppository. 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 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 32
Exclusion criteria
Exclusion criteria: 1. Any previous treatment for CML other than Hydroxyurea, Imatinib or Interferon alpha 2. Evidence of features of accelerated or blast phase at any time (by European Leu-kemia Net; at least one crit.) • Accelerated phase: o Blasts in blood or marrow 15-29%, or blasts plus promyelocytes in blood or marrow >30% with blasts 1mm in 2 or more leads and/or T wave inversions in 2 or more contiguous leads in screening ECG • Congenital long QT syndrome • QTc> 450 msec in the screening ECG • QT prolonging concomitant medication • History of or presence of significant ventricular or atrial tachyarrhythmia in screening ECG • History of or presence of clinically significant resting bradycardia (< 50 beats per minute) • Myocardial infarction within 12 months prior to informed consent • Unstable angina diagnosed or treated during the past 12 months before in-formed consent • Other clinically significant heart disease (e.g., congestive heart failure, uncon-trolled hypertension, history of labile hypertension) 12.Known HIV and/or hepatitis B or C infection (testing is not mandatory) 13.Other malignancies within the past 3 years before informed consent except for adequately treated carcinoma of the cervix and basal or squamous cell carcinoma of the skin 14.Women who are pregnant or breast feeding 15.Male/female patients of reproductive potential unwilling to practice a highly effec-tive method of birth control 16.History of noncompliance to medical regimens 17.Treatment with another investigational product during this study or during the last 30 days prior to informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Goal of the study is to investigate whether in patients with CML in chronic phase and confirmed MMR without MR4.5 receiving Imatinib at 400 to 800 mg daily a switch to Nilotinib at 300 mg twice daily results in a higher proportion of patients with con-firmed MR4 after two years of study treatment when compared with patients who continue receiving Imatinib (400 to 800 mg daily).;Secondary Objective: To determine -the cumulative incidence of MR4 and MR4.5 after one and two years of study treatment -and the proportion of patients with MR4 and MR4.5 lasting for at least two years -and the kinetics of BCR-ABL transcript levels over time -and the proportion of patients with confirmed MR4 two years after cross-over from Imatinib to Nilotinib in patients failing the primary endpoint in the Imatinib arm -and whether baseline clinical data are informative with respect to achievement of confirmed MR4 -and changes in the health-related Quality of Life -To investigate the predictive value of a previously developed mathematical model of CML treatment with respect to the patient-specific probability of reaching confirmed MR4 under continuous Imatinib -To collect data to establish a mathematical model regarding the prediction accuracy of the molecular relapse probability after treatment discontinuation (to be validated in DECLINEplus) -Study drug compliance;Primary end point(s): Proportion of patients with confirmed MR4 at two years of study treatment in both treatment arms. Confirmed MR4 at two years is defined as either BCR-ABL = 0.01% IS at 21 and 24 months or BCR-ABL = 0.01% IS at 24 months and confirmation with-in six weeks.;Timepoint(s) of evaluation of this end point: Month 21 and 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Cumulative incidence of confirmed MR4 after two years of study treatment. Confirmed MR4 is defined as BCR-ABL = 0.01% IS at two consecutive time points • Cumulative incidence of MR4and MR4.5 after one and two years of study treat-ment • Proportion of patients with MR4 lasting for at least one year, defined as BCR-ABL = 0.01% IS in at least three out of four consecutive 3-monthly measure-ments with first and last measurement showing MR4 • Proportion of patients with MR4 lasting for at least two years, defined as BCR-ABL = 0.01% IS in at least six out of eight consecutive 3-monthly measure-ments with first and last measurement showing MR4 • Proportion of patients with MR4.5 lasting for at least one year, defined as BCR-ABL = 0.0032% IS in at least three out of four consecutive 3-monthly meas-urements with first and last measurement showing MR4,5 • Proportion of patients with MR4.5 lasting for at least two years, defined as BCR-ABL = 0.0032% IS in at least six out of eight consecutive 3-monthly measure-ments with first and last measurement showing MR4,5 • Kinetics of BCR-ABL transcript levels over time • Proportion of patients with confirmed MR4 two years after cross-over from Imatinib to Nilotinib in patients failing the primary endpoint in the Imatinib arm (patients failing to achieve confirmed MR4 two years after randomisation and continued treatment with Imatinib) • Analysis of baseline clinical data which are informative with respect to achievement of confirmed MR4 • Application of a previously developed mathematical model to predict the pa-tient-specific probability of reaching confirmed MR4 under continuous Imatinib Study Code: DECLINE CAMN107ADE18T Version 3.0, 11.09..2015 Page 28 of 67 • To establish a mathematical model to predict molecular relapse probability af-ter treatment discontinuation (to be validated in DECLINEplus) • Analysis of changes in the health-related Quality of Life (EORTC-QLQ-C30, EORTC-QLQ-CML24) • Study drug comp | — |
Countries
Germany
Contacts
Public ContactClinical Trials Unit
University Medical Center Freiburg
Outcome results
None listed