Efficacy of asciminib in chronic phase CML patients with T315l mutations

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Friedrich-Schiller-Universitaet Jena

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-06-23

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Novartis Pharma GmbH

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

Reduction of molecular BCR::ABL1 levels (MR2) measured by PCR at month 12

Secondary objectives 6

1. Reduction of the size of the T315I positive BCR::ABL1 clone
2. Rate of MR2 by 12 months according to genetic background
3. Rate of molecular response (MR2, MMR, MR4, MR4.5; as assessed by BCR-ABLIS monitoring) at and by 6, 18, 24 months
4. Safety (adverse events)
5. Progression-free survival, probabilities of CML-related death, overall survival
6. Quality of life (measured by EORTC-standardized questionnaires)

Conditions and MedDRA coding

Chronic Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male or female patients with BCR::ABL1 positive CML in first or second chronic phase (i.e. after allogeneic stem cell transplantation) and proven T315I mutation detected by Sanger sequencing or NGS.
2. Age ≥ 18 years old (no upper age limit is given)
3. ECOG performance status of ≤2.
4. Serum levels of potassium, magnesium, total calcium within the normal limits (≥LLN [lower limit of normal] and ≤ULN [upper limit of normal]). Correction of electrolytes levels with supplements to fulfil enrolment criteria is allowed.
5. AST and ALT ≤2.5 x ULN or 5.0 x ULN if considered due to leukemia
6. Alkaline phosphatase ≤2.5 x ULN unless considered due to leukemia
7. Total bilirubin ≤1.5 x ULN, except known Gilbert disease
8. Serum creatinine ≤2 x ULN
9. Written informed consent prior to any study procedures being performed

Exclusion criteria 16

1. Pre-treatment with asciminib
2. BCR::ABL1 variants lacking ABL1 exon a2
3. Known impaired cardiac function, including any of the following: (1)Congenital long QT syndrome; (2)History of or presence of clinically significant ventricular or atrial tachyarrhythmia; (3)QTc >450 msec on screening ECG; (4)Myocardial infarction within 12 months prior to starting therapy
4. Other clinically significant heart disease (e.g., unstable angina, congestive heart failure)
5. Acute or chronic viral hepatitis with moderate or severe hepatic impairment (Child-Pugh scores >6), even if controlled
6. Other concurrent uncontrolled medical conditions (e.g., active or uncontrolled infections, acute or chronic liver and renal disease) that could cause unacceptable safety risks or compromise compliance with the protocol
7. Impaired gastrointestinal function or disease that may alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting and diarrhea, malabsorption syndrome, small bowel resection or gastric by-pass surgery)
8. Known chronic pancreatitis
9. Concomitant medications known to be strong inducers or inhibitors of the CYP450 isoenzyme CYP3A4
10. Patients who have undergone major surgery ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
11. Patients who are pregnant or breastfeeding or women of reproductive potential not employing an effective method of birth control. Women of childbearing potential must have a negative serum pregnancy test within 14 days of study start. Post-menopausal women must be amenorrheic for at least 12 months in order to be considered of non-childbearing potential.
12. Male and female patients must agree to employ an effective method of birth control throughout the study and for up to 2 weeks following discontinuation of study drug. (It is required that sexually active men use condom during intercourse while taking the drug and for 2 weeks after stopping treatment and not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Female partners of male patients must be advised to use highly effective methods of contraception.)
13. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
14. Active autoimmune disorder, including autoimmune hepatitis
15. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
16. Patients unwilling or unable to comply with the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. rate of MR2 at 12 months measured by BCR::ABL1 via PCR

Secondary endpoints 4

1. Reduction of the size of the T315I positive BCR::ABL1 clone by NGS measurement
2. Rate of molecular response assessed by BCR-ABLIS monitoring at and by 6, 18, 24 months
3. Progression-free survival, probabilities of CML-related death, overall survival at and by end of study
4. Quality of life at enrolment and months 3, 6, 9, 12, 18, and 24 after start with asciminib

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Friedrich-Schiller-Universitaet Jena

Sponsor organisation

Friedrich-Schiller-Universitaet Jena

Address

Am Klinikum 1, Lobeda Lobeda

City

Jena

Postcode

07747

Country

Germany

Scientific contact point

Organisation

Friedrich-Schiller-Universitaet Jena

Contact name

Prof. Thomas Ernst

Public contact point

Organisation

Friedrich-Schiller-Universitaet Jena

Contact name

Prof. Thomas Ernst

Locations

1 EU/EEA country · 8 investigational sites

By country

Investigational sites

Results and documents

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

Documents 8 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