Asciminib for children and teens with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase

A Phase II, Multicenter, Open-label, Single Arm Study to Evaluate the Safety and Efficacy of Asciminib in Pediatric Participants Newly Diagnosed or Previously Treated With Philadelphia Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP) With or Without Known T315I Mutation

This study will try asciminib as a treatment for children aged 1 to under 18 with Philadelphia chromosome–positive chronic myeloid leukemia in chronic phase, including newly diagnosed patients and those who are resistant or intolerant to prior TKIs, with or without the T315I mutation.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 1 Year to 18 Years
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Drugs / interventions: asciminib
• Locations: 2 sites (Brisbane, Queensland and 1 other locations)
• Trial ID: NCT07354074 on ClinicalTrials.gov

What this trial studies

This is a multi-center, open-label, single-arm Phase 2 trial enrolling pediatric participants aged 1 to under 18 with Ph+ CML in the chronic phase into three cohorts (newly diagnosed without T315I, resistant/intolerant without T315I, and any with known T315I). Participants will receive asciminib as a single agent using a pediatric weight‑based fed formulation or the adult fasted formulation depending on age/weight. There is no fixed treatment duration; the study will continue until five years after the last enrolled participant starts dosing to allow extended safety monitoring including growth and development. The primary focus is on clinical efficacy and safety outcomes in the pediatric population, with regular laboratory and molecular monitoring (BCR::ABL1) per protocol.

Who should consider this trial

Good fit: Children aged 1 to under 18 with cytogenetically confirmed Philadelphia chromosome–positive chronic-phase CML who are newly diagnosed within three months or who are resistant or intolerant to prior tyrosine kinase inhibitors, with or without the T315I mutation, are eligible.

Not a fit: Patients in accelerated or blast phase CML, those outside the 1 to <18 age range, or those who cannot attend required long-term follow-up visits are not likely to benefit from participation in this protocol.

Why it matters

Potential benefit: If successful, asciminib could offer an effective oral treatment option for children with Ph+ CML-CP, including those with T315I or who cannot tolerate or no longer respond to other TKIs.

How similar studies have performed: Asciminib has demonstrated efficacy and an acceptable safety profile in adult CML studies, particularly for TKI-resistant disease, but robust pediatric data are still limited.

Eligibility criteria

Key Inclusion Criteria:

Participants eligible for inclusion in this study must meet all of the following criteria:

1. Signed informed consent must be obtained prior to participation in the study.
2. Male or female participants 1 and \< 18 years of age at study enrollment
3. Diagnosis of CML-CP (Apperley et al 2025) with cytogenetic confirmation of Philadelphia positive (Ph+) chromosome
4. For participants with CML-CP newly diagnosed within 3 months of screening OR 5 For participants with CML - CP with high risk of developing resistance or intolerance to previous TKI:

   1. Unfavourable response to TKI is defined following the Apperley et al 2025 guidelines as:

      * At three months after the initiation of therapy: BCR::ABL1 ratio \> 10% IS (if confirmed within 1-3 months)
      * At six months after the initiation of therapy: BCR::ABL1 ratio \> 10% IS
      * At twelve months after initiation of therapy: BCR::ABL1 ratio \> 1% IS
      * At any time loss of previous response
      * At any time emergent resistant BCR::ABL1 mutations or high-risk ACA from prior TKI treatment as per local test results
   2. Intolerance to TKI is defined as:

      * Non-hematologic intolerance: participants with grade 3 or 4 toxicity while on therapy (in which case the patient is eligible whether or not there was a dose reduction); or with persistent grade 2 toxicity unresponsive to optimal management including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal)
      * Hematologic intolerance: participants with grade 3 or 4 toxicity (absolute neutrophil count \[ANC\] or platelets) while on therapy that is recurrent after dose reduction to the lowest doses of the TKI

6\. Evidence of typical BCR::ABL1 transcript \[e14a2 and/or e13a2\] at the time of screening which are amenable to standardized RQ-PCR quantification.

7\. Performance status: Karnofsky ≥ 50% for participants ≥ 16 years of age, and Lansky ≥ 50 for participants \< 16 years of age at the time of screening.

Key Exclusion Criteria:

1. Known second chronic phase (CP) of CML after previous progression to Accelerated Phase (AP)/Blast Phase (BP).
2. Previous treatment with a hematopoietic stem-cell transplantation.
3. Patient planned to undergo allogeneic hematopoietic stem cell transplantation
4. Known presence of a BCR::ABL1 mutation with known resistance to study treatment in accordance with the most recent public version of international CML clinical guidelines (e.g. NCCN CML treatment guidelines v 1.2026 and Apperley et al 2025) any time prior to study entry

Other inclusion/exclusion criteria may apply.

Where this trial is running

Brisbane, Queensland and 1 other locations

• Novartis Investigative Site — Brisbane, Queensland, Australia (Recruiting)
• Novartis Investigative Site — Seoul, South Korea (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Chronic Myelogenous Leukemia; Leukemia, Myelogenous, Chronic, Philadelphia Chromosome Positive; Asciminib; ABL001; Pediatric participants; Philadelphia chromosome positive chronic myeloid leukemia in chronic phase; Ph+ CML-CP; tyrosine kinase inhibitor