The trial aims to evaluate the efficacy and quality of life of nilotinib 300mg BID in patients with chronic myleoid leukemia in chronic phase. MedDRA version: 20.0 Level: LLT Classification code 10009700 Term: CML System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Tasigna 150 mg
Product Name: nilotinib
Product Code: AMN107
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Current Sponsor code: AMN107
Concentra
Sponsors
Novartis Pharma GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female patients at least 18 years of age 2. ECOG 0, 1, or 2. 3. Patients within 6 months of diagnosis of CML in chronic phase with cytogenetic confirmation of Ph+ [t(9;22) translocation]; if the bone marrow sample is taken within 12 weeks of the start of study treatment but before the patient consents, the bone marrow should not be repeated after the patient formally consents to the study. 4. Documented chronic phase CML will meet all the criteria defined by: 1. =65 years) yes F.1.3.1 Number of subjects for this age range 100
Exclusion criteria
Exclusion criteria: 1. Contraindication to excipients in study medication 2. Known impaired cardiac function, including any of the following: • Congenital long QT syndrome or a known family history of long QT syndrome • History of or presence of clinically significant ventricular or atrial tachyarrhythmias • Clinically significant resting bradycardia (450 msec (using the QTcF formula). If QTcF > 450 msec and electrolytes are not within normal ranges, electrolytes should be corrected and the patient re tested for the QTc • History of clinically documented myocardial infarction within 12 months prior to study entry • History of unstable angina during the last 12 months • Other clinical significant heart disease (congestive heart failure) 3. History of acute (within 1 year of starting study medication) or chronic pancreatitis 4. Severe and/or uncontrolled concurrent medical conditions that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g., acute artherothrombotic events (such as ischemic heart disease, acute peripheral arterial occlusive disease, symptomatic carotid stenosis/cerebrovascular accident), uncontrolled diabetes mellitus, active or uncontrolled infections, uncontrolled severe hypertension, and uncontrolled severe dyslipidemia, acute or chronic liver or severe renal disease. 5. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug 6. History of significant congenital or acquired bleeding disorder unrelated to cancer 7. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers (see http://medicine.iupui.edu/clinpharm/ddis/main-table/) or medications that have the potential to prolong the QT interval (see https://www.crediblemeds.org/pdftemp/pdf/CombinedList.pdf) which cannot be either discontinued or switched to a different medication prior to starting study drug 8. Patients who have not recovered from prior surgery 9. Patients who are: (a) pregnant, (b) breast feeding, (c) of childbearing potential without a negative pregnancy test prior to baseline and (d) female of childbearing potential unwilling to use contraceptive precautions throughout the trial (post- menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential). Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 14 days after the final dose of nilotinib. Patients using an oral hormonal contraception method should complete their monthly treatment course. Highly effective contraception methods include: • Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception • Female sterilization (surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment • Male sterilization (at least 6 months prior to screening). For fe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the proportion of patients who are in deep molecular response MR4.5 (IS) at 24 months of study treatment, measured in a standardized EUTOS MR4.5 laboratory. ;Secondary Objective: To determine the proportion of patients who are in deep molecular response MR4 (IS) at 24 months of study treatment. To determine the proportion of patients who are in MMR at 12 months of study treatment. To determine the proportion of patients who are in CCyR at 6 months of study treatment. To evaluate progression-free survival (PFS) and time to progression to AP/BC. To evaluate quality of life of 300mg nilotinib BID therapy. ;Primary end point(s): The primary efficacy variable is the rate of MR4.5 at 24 months of study treatment measured in a standardized EUTOS MR4.5 laboratory. MR4.5 is defined as either (i) detectable disease = 0.0032% BCR-ABLIS or (ii) undetectable disease in cDNA with 32 000 – 99 999 ABL1 transcripts or 77 000 – 239 999 GUSB transcripts.;Timepoint(s) of evaluation of this end point: evaluation will take place for all patients after 24 months of study treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): MR4 (IS) - MR4 (IS) is defined in this study as either (i) detectable disease =0.01% BCR-ABLIS or (ii) undetectable disease in cDNA with 10 000 – 31 999 ABL1 transcripts or 24.000 – 76 999 GUSB transcripts. - The rate of MR4 (IS) at 24 months of study treatment will be computed by dividing the number of patients who fit the definition of response at 24 months by the total number of patients in the analysis set. MMR - MMR is defined as a =3 log reduction from the standardized baseline or = 0.1% BCR-ABLIS - The rate of MMR at 12 months of study treatment will be computed by dividing the number of patients who fit the definition of response at 12 months by the total number of patients in the analysis set CCyR - Complete cytogenetic response is defined as 0% Ph+ metaphases - Rate of CCyR at 6 months of study treatment will be calculated by dividing the number of patients who fit the definition of response at 6 month by the total number of Ph+ patients in the analysis set Outcome - Time to progression to AP/BC is defined as the time from the date of start of study treatment to the date of earliest transformation to AP/BC, or CML-related death. Rates of progression at various time points will also be provided. - Progression-free survival is defined as the time from the date of start of study treatment to the date of event defined as the first documented disease progression to AP/BC or the date of death from any cause, whichever is earlier. ;Timepoint(s) of evaluation of this end point: evaluation will take place for all patients after 24 months of study treatment | — |
Countries
Germany
Contacts
Public ContactMedizinischer infoservice
Novartis Pharma GmbH
Outcome results
None listed