A multicenter trial where patients with CML stop medication a second time.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Uppsala

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15], Diseases [C] - Neoplasms [C04]

Trial duration

11 Jan 2018 → ongoing

Decision date (initial)

2025-01-27

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bristol-Myers Squibb

External identifiers

EU CT number

2024-515409-25-00

EudraCT number

2016-004106-34

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety

Assessment of treatment-free remission (persistence of MMR) after second attenmpt of TKI discontinuation in patients who failed a relapse in the EURO-SKI study or under EURO-SKI like conditions. Patients must have received at least three years of further TKI treatment of which the two last years should be dasatinib. The patients must have been in MR4 for a least one year.

Secondary objectives 4

1. Identification of clinical and biological factors correlating with the persistence of MMR or better after stopping TKI a second time.
2. Estimation of overall progression free survival
3. Time to re-achievement of MR4 after restart of therapy following a second molecular relapse
4. Assessment of incidence of any AEs (e.g. from treatment related musculoskeletal AE) that arise after stopping TKI treatment a second time

Conditions and MedDRA coding

Chronic myeloid leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. CML in CP under TKI treatment after failing a prior attempt to stop treatment within EURO-SKI or outside the study but according to EURO-SKI trial procedures. For the latter group this requires at least 3 years of TKI treatment (first line or second line due to intolerance to first line) before stop, and MR4 for at least one year before stopping
2. Treated with TKI for at least one year after having failed a prior attempt to stop TKI. Previous TKI can be any.
3. Typical BCR/ABL1 transcript (b3a2 and/or b2a2) must have been confirmed at diagnosis or later during the disease course.
4. 18 years or older

Exclusion criteria 12

1. Previous hematological relapse after first stop of TKI
2. Previous AP/BC at any time in the history of the disease
3. Restart of TKI without loss of MMR after first stop
4. Current participation i another clinical study
5. Previous or planned allogeneic stem cell transplantation
6. Patients with contra-indications to dasatinib therapy due to comorbidities
7. Subjects with acute hepatitis B virus HBV) infections
8. Uncontrolled or significant cardiovascular disease
9. Pulmonary arterial hypertension
10. Pleural or pericardial effusions of any grade at study entry
11. History of significant bleeding disorder unrelated to CML
12. A third stopping attempt

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The proportion of patients maintaining MMR at 6 and 12 months after discontinuing TKI a second time (survival without loss of major molecular response, MMR, defined as BCR-ABL1>0.1% on IS at one time point).

Secondary endpoints 4

1. Number of patients who re-achieved stable MR4, and were offered study participation; and overall and progression-free survival and the occurrence of a restart of TKI without prior molecular relapse.
2. Clinical and biological factors correlating with persistence of MMR or better after second TKI stop (BCR-ABL level before 2nd stop, Sokal score, gender, duration and type of TKI-treatment, duration of first TKI-stop, immunological biomarkers).
3. Time to reachievement of MR4 after second loss of MMR.
4. Adverse events related to second TKI stop, clinical and biological factors correlated to development of these AEs.

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Uppsala

Sponsor organisation

Region Uppsala

Address

Storgatan 27, Uppsala Domkyrkofors. Uppsala Domkyrkofors.

City

Uppsala

Postcode

753 31

Country

Sweden

Scientific contact point

Organisation

Region Uppsala

Contact name

Ulla Olsson-Strömberg

Public contact point

Organisation

Region Uppsala

Contact name

Ulla Olsson-Strömberg

Locations

3 EU/EEA countries · 4 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 9 files

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

Application history

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