Study to Determine the Efficacy and Safety of Asciminib in Pediatric Patients With Ph+ CML-CP

Novartis

Status and phase: Begins enrollment in 3 months; Phase 2

Conditions: Leukemia, Myelogenous, Chronic, Philadelphia Chromosome Positive; Chronic Myelogenous Leukemia

Treatments: Drug: Asciminib single agent

Study type: Interventional

Funder types: Industry

Identifiers

NCT07354074

2025-522138-29 (Registry Identifier)

CABL001I12202

Details and patient eligibility

About

The aim of this study is to support development of asciminib in the pediatric population (1 to < 18 years) with Ph+ CML-CP. The study will evaluate the efficacy and safety of asciminib in pediatric formulation (weigh-based dose, fed state) or adult formulation (fasted) in newly diagnosed and resistant or intolerant Ph+ CML-CP with or without T315I mutation.

Full description

This is a multi-center, open-label, single arm study of asciminib in pediatric participants aged

1 to <18 years old with Ph+ CML-CP newly diagnosed and previously treated with TKI treatment, with or without T315I mutation.

The study population will consist of three cohorts of Ph+ CML-CP pediatric participants:

• Newly-diagnosed Ph+ CML-CP participants without known T315I mutation
• Ph+ CML-CP participants resistant or intolerant to previous TKI without known T315I mutation
• Ph+ CML-CP participants with known T315I mutation irrespective of prior TKI treatment

There is no fixed duration of study treatment for the participants. The study will end 5 years (240 weeks) after the last enrolled participants received their first dose of treatment in the study. The objective is to have enough follow up for safety, including growth and development and efficacy.

Enrollment: 50 estimated patients

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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50 participants in 1 patient group

Single arm study

Experimental group

Description:

This study will enroll pediatric patients (≥ 1 and \< 18 years of age) with newly diagnosed or previously treated with Philadelphia positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP) with or without known T315I mutation

Treatment:

Drug: Asciminib single agent