Efficacy of Asciminib in Chronic Phase CML Patients With T315I Mutations (ESTIMATION)

This is a multi-center, prospective, single-arm, non-randomized, interventional phase II study of CML patients in first or second chronic phase (i.e. after allogeneic stem cell transplantation) and proven BCR::ABL1 T315I mutation. All patients will be treated with asciminib 200 mg BID. 50 patients will be enrolled from approximately 20 study sites in Germany.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Myeloid Leukemia (CML)
• Intervention / Treatment: Drug: asciminib 200 mg BID

Detailed Description

This is a multi-center, prospective, single-arm, non-randomized, interventional phase II study of CML patients in first or second chronic phase (i.e. after allogeneic stem cell transplantation) and proven BCR::ABL1 T315I mutation. All patients will be treated with asciminib 200 mg BID. 50 patients will be enrolled from approximately 20 study sites in Germany.

Total maximum study duration is anticipated to be approximately 4 years. This includes an enrolment period of approximately 24 months and a minimum of 24 months of treatment with asciminib. The study will continue for 24 months from the date of the last patient enrolled. Enrolled patients will be followed for the duration of the study, death or withdrawal from participation. Patients who discontinue treatment during the study will also be followed for the duration of the study, including those, who changed anticancer therapy. Patients who experience an AE within the 30 days post discontinuation will be followed in particular to determine the consequences of the AE.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Jena, Germany, 07747
    • Universitatsklinikum Jena

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 mutations detected by Sanger sequencing or NGS.
• Age ≥ 18 years old (no upper age limit is given)
• ECOG performance status of ≤2.
• 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:

• Pre-treatment with asciminib
• BCR::ABL1 variants lacking ABL1 exon a2

• 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 clinically 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)
• Known chronic pancreatitis
• 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. (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.)
• Known diagnosis of human immunodeficiency virus (HIV) infection (HIV testing is not mandatory)
• Active autoimmune disorder, including autoimmune hepatitis
• Patients with a history of another primary malignancy that is currently clinically significant or currently requires active intervention
• hypersensitivity to the active ingredient asciminib or to any of the other ingredients listed according to the latest version of the SmPC
• Patients unwilling or unable to comply with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: asciminib 200 mg BID; All patients will be treated with asciminib 200 mg BID	Drug: asciminib 200 mg BID; All patients will be treated with asciminib 200 mg BID.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of MR2 at 12 months	rate of response after 12 months	12 months after start of therapy

Collaborators and Investigators

• Sponsor: Thomas Ernst, PD Dr. med.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: August 24, 2026
• First Submitted That Met QC Criteria: August 24, 2026
• First Posted (Actual): August 27, 2026

Study Record Updates

• Last Update Posted (Actual): August 27, 2026
• Last Update Submitted That Met QC Criteria: August 24, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia; Myeloproliferative Disorders; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; BID protein, human; asciminib
• Other Study ID Numbers: ESTIMATION; 2025 (U.S. NIH Grant/Contract: Faculty of Social Sciences Scientific Grant at the University of Gdańsk); 2025-523491-23-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No