Frontline Asciminib combination in chronic phase CML

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] - Hemic and Lymphatic Diseases [C15]

Trial duration

8 Oct 2024 → ongoing

Decision date (initial)

2024-10-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-516212-24-00

EudraCT number

2018-002256-33

ClinicalTrials.gov

NCT03906292

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy

Achievement of deep molecular response (MR4) with the combination of ATP competing BCR‐ABL1 inhibitors with asciminib in newly diagnosed CML patients

Conditions and MedDRA coding

Chronic Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Male or female patients with diagnosis of CP‐CML with cytogenetic confirmation of the Ph+ chromosome [t(9;22)(q34;q11)]
2. Ph‐negative cases or patients with variant translocations who are BCR‐ABL1 positive in multiplex PCR will be also considered eligible
3. ECOG performance status of ≤2
4. Age ≥ 18 years old (no upper age limit is given)
5. 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
6. AST and ALT ≤2.5 x ULN or 5.0 x ULN if considered due to leukemia
7. Alkaline phosphatase ≤2.5 x ULN unless considered due to leukemia
8. Total bilirubin ≤1.5 x ULN, except known Gilbert disease
9. Serum creatinine ≤2 x ULN
10. Serum lipase ≤1.5 x ULN
11. Written informed consent prior to any study procedures being performed

Exclusion criteria 17

1. Allogeneic stem cell transplantation
2. Known impaired cardiac function, including any of the following: o Congenital long QT syndrome o History of or presence of clinically significant ventricular or atrial tachyarrhythmia o QTc >450 ms on screening ECG o Myocardial infarction within 12 months prior to starting therapy o History of clinically significant/ symptomatic bradycardia o Family history of idiopathic sudden death
3. Patients with resting QTcF ≥450 msec (male) or ≥460 msec (female) at pretreatment, or inability to determine the QTcF interval
4. Patients with uncorrected hypokalemia or hypomagnesemia
5. Other clinically significant heart disease (e.g. unstable angina, congestive heart failure)
6. Acute or chronic viral hepatitis with moderate or severe hepatic impairment (Child‐Pugh scores >6), even if controlled
7. 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
8. 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)
9. History of acute or chronic pancreatitis
10. Concomitant medications known to be strong inducers or inhibitors of the CYP450 isoenzyme CYP3A4
11. Patients who have undergone major surgery ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
12. 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.
13. 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.)
14. Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
15. Known serious hypersensitivity reactions to asciminib, imatinib, nilotinib or dasatinib
16. Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
17. Patients unwilling or unable to comply with the protocol

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Rate of MR4 at month 12

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 · 20 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 5 files

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

Application history

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