NEWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA MedDRA version: 21.0 Level: LLT Classification code 10000845 Term: Acute lymphoblastic leukemia System Organ Class: 100000004864
Conditions
Interventions
Trade Name: ICLUSIG 15 mg film-coated tablets
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ponatinib
CAS Number: 943319-70-8
Other descriptive name: PONATINIB
Concentration unit: mg mi
Sponsors
Ústav hematologie a krevní transfuze
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with newly diagnosed, previously untreated, Ph-positive [either t(9;22) and/or BCR-ABL positive] B-precursor acute lymphoblastic leukemia; • Age 18-65 years; • Eligible to intensive chemotherapy, due to general health status; • ECOG performance status =2; • Absence of significant liver disease, as defined by the following criteria: total serum bilirubin =1.5 x upper limit of normal (ULN), unless due to Gilbert's syndrome, alanine aminotransferase (ALT) =2.5 × ULN or =5 x ULN if leukemic involvement of the liver is present, and aspartate aminotransferase (AST) =2.5 × ULN or =5 x ULN if leukemic involvement of the liver is present; • Adequate pancreatic function as defined by serum amylase and lipase =1.5 × ULN; • Diagnostic sample of bone marrow (or peripheral blood with >50% of blasts) available for central MRD assessment; • Subject has provided written informed consent prior to any screening procedure. 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 32 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • Lymphoid blast crisis of CML; • Active serious infection not controlled by oral or intravenous antibiotics; • Active known HBV or HCV hepatitis or positive HIV serology; • History of acute pancreatitis within 1 year of study or history of chronic pancreatitis; • Uncontrolled hypertriglyceridemia (triglycerides >5.1 µmol/L); • Clinically significant, uncontrolled or active cardiovascular disease, specifically including, but not restricted to: any history of myocardial infarction, stroke, or revascularization; unstable angina or transient ischemic attack within 6 months prior to enrolment; congestive heart failure within 6 months prior to enrolment or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards; history of clinically significant (as determined by the treating physician) atrial arrhythmia; any history of ventricular arrhythmia; any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism; • Uncontrolled hypertension (diastolic blood pressure >90 mmHg; systolic >140 mmHg). Patients with hypertension should be under treatment on study entry to effect blood pressure control; • Creatinine levels > 160 µmol/L or estimated creatinine clearance of<50 mL/min; • GI disease and/or major GI surgery that may significantly alter the absorption of study drug; • Hypersensitivity to the active substance or to any of the excipients, especially galactose intolerance; • Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib (see chapter 4.5 of Iclusig SPC attached to the protocol) • Female patients who are pregnant or breast feeding or patients of childbearing potential not willing to use a highly effective method of contraception during the study and for 3 months following the last dose of study drug; • Male patients whose sexual partner(s) are women of childbearing potential who are not willing to use a highly effective method of contraception, one of which includes a condom, during the study; • Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention; • Any concurrent severe and/or uncontrolled medical condition, which could, in the opinion of the investigator, compromise participation in the study; • Concurrent participation in another clinical study with an investigational medical product.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the percentage of complete molecular responses after two cycles of induction therapy composed of chemotherapy plus ponatinib;Secondary Objective: To evaluate rate of complete remissions (CR and/or CRi) after the first and second cycles of remission induction therapy; To evaluate progression-free survival (PFS) in patients treated with ponatinib plus reduced-intensity chemotherapy; To evaluate overall survival (OS) in patients treated with ponatinib plus reduced-intensity chemotherapy; To determine the percentage of patients undergoing allogeneic stem cell transplantation (alloSCT) due to the suboptimal molecular response after two cycles of ponatinib-based induction regimen; To evaluate the incidence and seriousness of adverse events;Primary end point(s): MRD response after two cycles of induction therapy plus ponatinib;Timepoint(s) of evaluation of this end point: After completion of two cycles of induction therapy composed of reduced chemotherapy plus ponatinib; Week 11 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Complete remission (CR and/or CRi) at the end of Induction cycle I and Induction cycle II; 2. Progression-free survival (PFS); 3. Overall survival (OS); 4. AlloSCT in the first complete remission; 5. Severity of adverse events during and up to 30 days after end of ponatinib treatment. ;Timepoint(s) of evaluation of this end point: 1. CR and CRi at the end of Inducton cycle 1 and II 2. PFS till date of Relapse 3. Time of death 4. AlloSCT 5. Ocurence and severity of Adverse Event during ponatinib treatment including 30 days after EoT | — |
Countries
Czech Republic
Contacts
Public ContactCyril Šálek, MUDr. Mgr. Ph.D.
Ústav hematologie a krevní transfuze
Outcome results
None listed