Ponatinib Plus Reduced-intensity Chemotherapy in the First-line Treatment of Adult Patients With Ph+ ALL (Pona-CELL)

This is an interventional treatment trial for Acute Lymphoblastic Leukemia, Adult Read More

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 more than 18 years;
• Eligible to intensive chemotherapy, due to general health status;
• ECOG (Eastern Cooperative Oncology Group) 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.

Exclusion Criteria:

• Lymphoid blast crisis of chronic myelocytic leukemia (CML);
• Active serious infection not controlled by oral or intravenous antibiotics;
• Active known hepatitis B virus (HBV) or hepatitis C virus (HCV) 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;
• 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.