With Ponatinib on the track for treatment-free-remission in chronic myeloid leukemia

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Heidelberg University

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Not possible to specify, Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

21 Dec 2024 → 5 Feb 2026

Decision date (initial)

2024-11-22

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Incyte Biosciences International Sarl

External identifiers

EU CT number

2024-518971-76-00

EudraCT number

2018-004564-59

WHO UTN

U1111-1240-5511

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

Assessment of patients who achieved MR4 after 2 years of treatment with ponatinib.

Secondary objectives 7

1. Molecular status (no MMR, MMR, MR4, and MR4.5) at the evaluation times defined in the visit schedule
2. Time from inclusion to first MR4 and to first MR4.5
3. Assessment of safety profile, tolerability and adverse events under ponatinib treatment
4. Assessment of health-related quality of life (QoL) profiles under ponatinib treatment
5. 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
6. Evaluation of medico-economic impact of ponatinib therapy with the possibility of a TFR approach
7. Evaluation of overall survival and progression-free survival

Conditions and MedDRA coding

chronic myeloid leukemia in chronic phase

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Female or male ≥ 18 years of age
2. Patients with CML in chronic phase (CP)
3. BCR-ABL IS between 0,5-0,01 and demonstrated by the last PCR before inclusion
4. 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
5. Philadelphia -chromosome and/or BCR-ABL (either b3a2 and /or b2a2) fusion gene positive CML
6. Patients must have had an eye examination including fundoscopy by an ophthalmologist within 8 weeks prior to first treatment

Exclusion criteria 44

1. Failure of any TKI at any time during CML treatment according to current ELN criteria (including any detection of mutations or additional cytogenetic aberrations)
2. Prior diagnosis of accelerated phase (AP) or blast phase (BP) at any time in the history of the disease
3. Previously planned or performed allogenic SCT
4. High cardiac risk according to ESC score (≥ 10%) (results of screening)
5. Clinically significant resting bradycardia (<50 bpm) or tachycardia (>100 bpm) (results of screening)
6. QTcF interval on baseline electrocardiogram (ECG) evaluation, defined as QTcF of >450 ms in males or > 470 ms in females (results of screening)
7. Treatment with inhibitors of CYP3A4 or medications that have been well documented to prolong the QT interval
8. 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
9. Ankle-brachial-index (ABI) < 0,9 or >1,4 or alternatively signs of arterial occlusion in duplex sonography
10. 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)
11. Positive hepatitis B virus serology test
12. No adequate pancreatic function (serum lipase and amylase >1.5 × ULN)
13. No adequate renal function [estimated creatinine clearance (eGFR) of < 90 ml/min
14. Other severe or uncontrolled medical conditions(e.g. Infection)
15. Women who are pregnant or breast feeding
16. positive serum pregnancy test (of woman with childbearing potential)
17. 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.
18. Legally incapacitated
19. No ability to comprehend and sign the informed consent.
20. Held in an institution by legal or official order
21. Not able to take oral therapy
22. No willingness or ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
23. Participation in other clinical trials
24. History of myocardial infarction
25. History of significant (as determined by the treating physician) atrial or ventricular arrhythmias
26. History of coronary heart disease
27. History of congenital long QT syndrome or family
28. Use of a ventricular paced pacemaker
29. History of other clinically significant heart disease (e.g. unstable angina, congestive heart failure) or impaired cardiac function
30. History of hyperlipidaemia
31. History of cerebrovascular accident (CVA, e.g. stroke) or transient ischemic attack (TIA)
32. History of peripheral vascular infarction, including visceral infarction or other vascular occlusive events
33. History of any revascularization procedure, (e.g. placement of stents, bypasses)
34. Venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 6 months prior to enrolment
35. Historiy of retinal venous occlusions
36. History of moderate or severe acute or chronic liver disease
37. History of alcohol abuse
38. History of severe hypertriglyceridemia
39. Either acute pancreatitis within 1 year before study entry or chronic pancreatitis
40. Renal artery stenosis
41. Moderate , severe or end-stage chronic renal disease unrelated to tumor
42. Severe diabetes with end organ damage (e.g. microalbuminuria) or poorly controlled diabetes, defined as HbA1c values over the previous year of > 7.5% (59 mmol/mol) on more than 3 occasions. Patients with pre-existing, well-controlled diabetes are not excluded.
43. Bleeding issues
44. Any other malignancy except if neither clinically significant nor requires active intervention.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MR4 after 24 months of ponatinib treatment

Secondary endpoints 7

1. Molecular status (no MMR, MMR, MR4, and MR4.5) at the evaluation times defined in the visit schedule
2. Time from inclusion to first MR4 and to first MR4.5
3. Safety profile, tolerability and adverse events under ponatinib treatment
4. Health-related quality of life (QoL) under ponatinib treatment
5. 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
6. Evaluation of medico-economic impact of ponatinib therapy with the possibility of a TFR approach
7. Evaluation of overall survival and progression-free survival

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Heidelberg University

Sponsor organisation

Heidelberg University

Address

Seminarstrasse 2, Altstadt Altstadt

City

Heidelberg

Postcode

69117

Country

Germany

Scientific contact point

Organisation

Heidelberg University

Contact name

Prof. Dr. med. Susanne Saußele

Public contact point

Organisation

Heidelberg University

Contact name

Prof. Dr. med. Susanne Saußele

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications