WITH PONATINIB ON THE TRACK FOR TREATMENT-FREE-REMISSIONIN CHRONIC MYELOID LEUKEMIA

Phase 1

• Conditions: chronic myeloid leukemia in chronic phase; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2018-004564-59-DE
• Lead Sponsor: Heidelberg University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-15
• Last Update Posted: 8 March 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 60

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 < 0,01% BCR-ABLIS) or not achieving a stable MR4 (defined as no continuous in MR4 during the last 12 months before inclusion) after = 3 years of treatment with nilotinib, dasatinib and / or bosutinib in first or second line
?Philadelphia -chromosome and/or BCR-ABL (either b3a2 and /or b2a2) fusion gene positive CML
?Patients must have had an eye examination including fundoscopy by an ophthalmologist within 8 weeks prior to first treatment

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 55
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 5

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 (<50 bpm)
•QTcF interval on baseline electrocardiogram (ECG) evaluation, defined as QTcF of >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) < 0,9 or >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

Study & Design

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