Chronic Myeloid Leukemia MedDRA version: 19.0 Level: LLT Classification code 10009700 Term: CML System Organ Class: 100000004864
Conditions
Interventions
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: DASATINIB
CAS Number: 302962-49-8
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 100-
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 PCR4 will be also considered eligible. • ECOG performance status =2. • Age = 18 years old (no upper age limit is given) • Serum levels of potassium, and total calcium within the normal limits (=LLN [lower limit of normal] and =ULN [upper limit of normal]). Correction of electrolytes’ levels with supplements to meet enrolment criteria is allowed. • AST and ALT =2.5 x ULN 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 Gilbert disease • Serum creatinine =2 x ULN • Written informed consent prior to any study procedures being performed. For 1st-line patients: • Pre-treatment with hydroxyurea up to 6 months and imatinib or dasatinib for a duration of up to 4 weeks is permitted. For = 2nd-line patients • Patients with treatment failure according to the 2013 ELN Guidelines criteria3 or treatment intolerance as assessed by the investigator after prior treatment with TKIs other than dasatinib (imatinib, nilotinib, bosutinib, ponatinib). 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 106 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 200
Exclusion criteria
Exclusion criteria: • Previous allogeneic stem cell transplantation (AlloSCT) • Known impaired cardiac function, including any of the following: o Congenital long QT syndrome o History of or presence of clinically significant ventricular or atrial tachyarrhythmia o QTc >450 msec on screening ECG o Myocardial infarction within 6 months prior to starting therapy • Other clinical significant heart disease (e.g. unstable angina, congestive heart failure) • 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., 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 diarrhoea, malabsorption syndrome, small bowel resection or gastric by-pass surgery) • Concomitant medications known to be strong inducers or inhibitors of the CYP450 isoenzyme CYP3A4 • 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 breastfeeding 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 dasatinib. Post-menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential. Male and female patients must agree to employ an effective 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 dasatinib • 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: - The cumulative toxicity score after two years of dasatinib treatment. - Rate of major molecular response (MMR) as assessed by BCR-ABL -monitoring by 24 months ;Secondary Objective: - Rate of molecular response (as assessed by BCR-ABL monitoring) at 6 and 12 months - Quality of life assessment ;Primary end point(s): - cumulative toxicity score - Rate of molecular response ;Timepoint(s) of evaluation of this end point: - month 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Rate of molecular Response 2 - Quality of life assessment ;Timepoint(s) of evaluation of this end point: 1 - months 6 and 12 2 - days 0, 84; months 6, 12, 24 | — |
Countries
Germany
Contacts
Public ContactCML-Study Group
CML-Study Group
Outcome results
None listed