chronic myeloid leukemia in chronic phase
Conditions
Interventions
Trade Name: Iclusig
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: ponatinib
CAS Number: 1114544-31-8
Other descriptive name: PONATINIB HYDROCHLORIDE
Concentration unit: g gram(s)
Concen
Sponsors
Heidelberg University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Female or male = 18 years of age ? Patients with CML in chronic phase (CP) ? BCR-ABLIS between 0,5-0,01 and demonstrated by the last PCR before inclusion ? not achieving MR4 (defined as =65 years) no F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: ? Failure of any TKI at any time during CML treatment according to current ELN criteria (including any detection of mutations or additional cytogenetic aberrations) ? Prior diagnosis of accelerated phase (AP) or blast phase (BP) at any time in the history of the disease ? Previously planned or performed allogenic SCT ? At time of inclusion (results of screening) • High cardiac risk according to ESC score (= 10%) • Clinically significant resting bradycardia (450 ms in males or > 470 ms in females. • Treatment with inhibitors of CYP3A4 or medications that have been well documented to prolong the QT interval (see chapter V.4.5) • Uncontrolled hypertension (diastolic blood pressure = 90 mm Hg; systolic = 140 mm Hg). Patients with hypertension should be under treatment on study entry to effect blood pressure control • Ankle-brachial-index (ABI) 1,4 or alternatively signs of arterial occlusion in duplex sonography • No adequate hepatic function (total serum bilirubin > 1.5 × ULN, unless due to Gilbert’s syndrome; Alanine aminotransferase (ALAT) > 2.5 × ULN, or > 5 × ULN if leukemic infiltration of the liver is present; aspartate aminotransferase (ASAT) > 2.5 × ULN, or > 5 × ULN if leukemic infiltration of the liver is present) • Positive hepatitis B virus serology test • No adequate pancreatic function (serum lipase and amylase >1.5 × ULN) • No adequate renal function [estimated creatinine clearance (eGFR) of < 50 ml/min, Cockcroft and Gault Score] • Other severe or uncontrolled medical conditions(e.g. Infection) • Women who are pregnant or breast feeding • positive serum pregnancy test (of woman with childbearing potential, see page 59) • woman of childbearing potential not agreeing to use an higly-effective form of contraception or fertile male not agreeing to use an acceptable birth control method (for definition see appendix) with sexual partners throughout study participation until 90 days after EoT. • Legally incapacitated • No ability to comprehend and sign the informed consent. • Held in an institution by legal or official order • Not able to take oral therapy • No willingness or ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures. • Participation in other clinical trials ? History of • myocardial infarction (MI) • clinically significant (as determined by the treating physician) atrial or ventricular arrhythmias • coronary heart disease • congenital long QT syndrome or family history of • use of a ventricular paced pacemaker • other clinically significant heart disease (e.g. unstable angina, congestive heart failure) or impaired cardiac function • hyperlipidaemia. • cerebrovascular accident (CVA, e.g. stroke) or transient ischemic attack (TIA) • peripheral vascular infarction, including visceral infarction or other vascular occlusive events • any revascularization procedure, (e.g. placement of stents, bypasses) • venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 6 months prior to enrolment • retinal venous occlusions • Moderate or severe acute or chronic liver disease • alcohol abuse. • severe hypertriglyceridemia • either acute pancreatitis within 1 year before study entry or chronic pancreatitis • renal artery stenosis • moderate , severe or end-stage chronic renal disease unrelated to tumor • severe diabetes with end organ da
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The main purpose of the study is the assessment of patients who are in MR4 or deeper after 2 years of ponatinib treatment.;Secondary Objective: Secondary objectives of the study are Molecular status (no MMR, MMR, MR4, and MR4.5) at the evaluation times defined in the visit schedule Time from inclusion to first MR4 and to first MR4.5 Assessment of safety profile, tolerability and adverse events under ponatinib treatment Assessment of health-related quality of life (QoL) profiles under ponatinib treatment Identification of clinical and biological factors associated with the achievement of MR4 or better under ponatinib (e.g. risk scores (Sokal/Euro/EUTOS/ELTS), gender, duration of TKI treatment, molecular level at study entry) Evaluation of medico-economic impact of ponatinib therapy with the possibility of a TFR approach Evaluation of overall survival and progression-free survival ;Primary end point(s): Treatment with Ponatinib for 2 years; see primary objectives;Timepoint(s) of evaluation of this end point: endpoint for each patient after 2 years of treatment with Ponatinib | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Treatment with Ponatinib for 2 years; see secondary objectives;Timepoint(s) of evaluation of this end point: Inclusion of the last patient into the study plus 2 years of treatment | — |
Countries
Germany
Contacts
Public ContactCoordinating Investigator
Heidelberg University
Outcome results
None listed