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

Phase 2RecruitingNCT07354074

Novartis Pharmaceuticals50 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Chronic Myelogenous Leukemia Leukemia, Myelogenous, Chronic, Philadelphia Chromosome Positive

Interventions

Asciminib single agentDRUG

Asciminib (labelled as ABL001) administered as 40 mg tablet (adult formulation) or as 1 mg film-coated granules mini-tablets (pediatric formulation)

Eligibility

Sex: ALLMin age: 1 YearMax age: 18 Years

Medical Language ↔ Plain English

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.

Locations (4)

Novartis Investigative Site

Brisbane, Queensland, Australia

RECRUITING

Novartis Investigative Site

Montreal, Quebec, Canada

RECRUITING

Novartis Investigative Site

Seoul, South Korea

RECRUITING

Outcomes

Primary Outcomes

MMR at Week 48

MMR is defined as BCR::ABL1 IS ≤0.1%. MMR is defined as a ≥ 3.0 log reduction in BCR::ABL1 transcripts compared to the standardized baseline equivalent to ≤ 0.1 % BCR::ABL1/ABL % by international scale as measured by RQ-PCR.

Time frame: 48 weeks

Secondary Outcomes

MMR at Week 96

Time frame: 96 weeks

MMR at and by scheduled timepoints

Time frame: Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96

Hematologic response at and by scheduled timepoints

Complete hematologic response (CHR) is defined as all of the following present for ≥ 4 weeks (which means present at least at 2 visits 4-week apart, with no intermediate visit showing no CHR): * White blood cell(s) (WBC) count \< 10 x 10\^9/L * Platelet count \< 450 x 10\^9/L * Basophils \< 5% * No blasts and promyelocytes in peripheral blood * Myelocytes + metamyelocytes \< 5% in peripheral blood * No evidence of extramedullary disease, including spleen and liver

Time frame: Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96

Cytogenetic response at and by scheduled timepoints

Cytogenetic response is defined as follows: * Complete (CCyR) - 0% Ph+ metaphases * Partial (PCyR) - \>0 to 35% Ph+ metaphases * Major\* (MCyR) - 0 to 35% Ph+ metaphases * Minor (mCyR) - \>35 to 65% Ph+ metaphases * Minimal - \>65 to 95% Ph+ metaphases * None - \>95 to 100% Ph+ metaphases Bone marrow aspirate for cytogenetic analyses will be performed at screening, and upon unfavorable response to treatment at the physician's discretion.

Central Contacts

Novartis Pharmaceuticals

CONTACT

1-888-669-6682 novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Data from ClinicalTrials.gov

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