Frontline Asciminib Combination in Chronic Phase CML

• Status: Recruiting
• Trial end date: 2027-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Adult male and female patients with newly diagnosed Philadelphia chromosome positive (Ph+) and/or BCR-ABL1 positive CML can be included in the study until 3 months after diagnosis. A <4 week pretreatment with hydroxyurea is permitted. Patients treated for <6 weeks with nilotinib 300 mg BID, imatinib 400 mg QD, dasatinib 100 mg QD or without any therapy are eligible for recruitment and will be allocated to the respective cohort. All patients must provide written informed consent to be enrolled in the trial. Cohorts were designed to allow assessment of QD and BID asciminib based combinations to optimize quality of life and compliance. Patients will not be randomized. In general, cohorts will be filled consecutively. Asciminib therapy will be commenced 12 weeks after start of nilotinib, imatinib or dasatinib and after recovery of hematopoiesis or in case of no therapy so far 6 weeks after diagnosis as first line treatment. Referred patients already treated with imatinib, nilotinib or dasatinib will remain on the initial drug and will be allocated to the respective cohort.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Prof. Dr. med. Andreas Hochhaus; University of Jena
• Collaborators: Ludwig-Maximilians - University of Munich; Novartis Pharmaceuticals
• Treatments: Dasatinib; Imatinib Mesylate; Niacinamide

Criteria

Inclusion Criteria:

• Male or female patients with diagnosis of CP-CML with cytogenetic confirmation of the Ph+ chromosome [t(9;22)(q34;q11)].

• Ph-negative cases or patients with variant translocations who are BCR-ABL1 positive in multiplex PCR 35 will be also considered eligible.

• ECOG performance status of ≤2.

• Age ≥ 18 years old (no upper age limit is given)

• 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.

• AST and ALT ≤2.5 x ULN or 5.0 x ULN if considered due to leukemia

• Alkaline phosphatase ≤2.5 x ULN unless considered due to leukemia

• Total bilirubin ≤1.5 x ULN, except known Gilbert disease

• Serum creatinine ≤2 x ULN

• Written informed consent prior to any study procedures being performed.

Exclusion Criteria:

• Allogeneic stem cell transplantation

• Known impaired cardiac function, including any of the following:

• Congenital long QT syndrome

• History of or presence of clinically significant ventricular or atrial tachyarrhythmia

• QTc >450 msec on screening ECG

• Myocardial infarction within 12 months prior to starting therapy

• Other clinical significant heart disease (e.g. unstable angina, congestive heart failure)

• Acute or chronic viral hepatitis with moderate or severe hepatic impairment (Child-Pugh scores >6), even if controlled

• 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

• 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)

• Concomitant medications known to be strong inducers or inhibitors of the CYP450 isoenzyme CYP3A4

• Patients who have undergone major surgery ≤2 weeks prior to starting study drug or who have not recovered from side effects of such therapy

• 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. 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

• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)

• Known serious hypersensitivity reactions to asciminib, imatinib, nilotinib or dasatinib

• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention

• Patients unwilling or unable to comply with the protocol.