The effectivness and safety of ponatinib administered in combination with reduced chemotherapy in treatment of acute lymphoblastic leukemia in adults.

Phase 1

• Conditions: EWLY DIAGNOSED PHILADELPHIA CHROMOSOME-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA; MedDRA version: 21.0Level: LLTClassification code 10000845Term: Acute lymphoblastic leukemiaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2019-004540-29-CZ
• Lead Sponsor: Ústav hematologie a krevní transfuze

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-07-07
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 32

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

• 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified