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

Official title

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

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.

Detailed 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.

Interventions

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

Primary outcome measures

• MMR at Week 48 [Time frame: 48 weeks]

Secondary outcome measures (12)

• 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 [Time frame: Weeks 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96]
• Cytogenetic response at and by scheduled timepoints [Time frame: 5 years]
• Time to response [Time frame: 240 weeks after the last participant enrolled in the study received the first dose of treatment]
• Duration of response (limited to the binary response endpoints) [Time frame: 240 weeks after the last participant enrolled in the study received the first dose of treatment]
• Time to treatment failure (TTF) [Time frame: 240 weeks after the last participant enrolled in the study received the first dose of treatment]
• Time to disease progression [Time frame: 5 years]
• Event-free survival (EFS) [Time frame: 240 weeks after the last participant enrolled in the study received the first dose of treatment]
• Overall survival (OS) [Time frame: 240 weeks after the last participant enrolled in the study received the first dose of treatment]
• Growth: Height/length, weight, bone age measured by X-Ray [Time frame: 240 weeks after the last participant enrolled in the study received the first dose of treatment]
• Sexual maturation: Height/length, weight, bone age measured by Tanner staging [Time frame: 240 weeks after the last participant enrolled in the study received the first dose of treatment]

Eligibility criteria

Inclusion criteria

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

• Signed informed consent must be obtained prior to participation in the study.
• Male or female participants 1 and < 18 years of age at study enrollment
• Diagnosis of CML-CP (Apperley et al 2025) with cytogenetic confirmation of Philadelphia positive (Ph+) chromosome
• 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:

• 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
• 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.

Exclusion criteria

• Known second chronic phase (CP) of CML after previous progression to Accelerated Phase (AP)/Blast Phase (BP).
• Previous treatment with a hematopoietic stem-cell transplantation.
• Patient planned to undergo allogeneic hematopoietic stem cell transplantation
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 4 centers

• Novartis Investigative Site — Marseille
• Novartis Investigative Site — Paris
• Novartis Investigative Site — Poitiers
• Novartis Investigative Site — Strasbourg

United States · 3 centers

• Rutgers Cancer Institute of New Jersey — New Brunswick
• Columbia University Medical Center New York Presbyterian — New York
• Seattle Childrens Hospital — Seattle

Japan · 3 centers

• Novartis Investigative Site — Yokohama
• Novartis Investigative Site — Fukuoka
• Novartis Investigative Site — Saitama

Australia · 2 centers

• Novartis Investigative Site — Brisbane
• Novartis Investigative Site — North Adelaide

Canada · 2 centers

• Novartis Investigative Site — Edmonton
• Novartis Investigative Site — Montreal

China · 2 centers

• Novartis Investigative Site — Zhengzhou
• Novartis Investigative Site — Tianjin

Poland · 2 centers

• Novartis Investigative Site — Gdansk
• Novartis Investigative Site — Wroclaw

South Korea · 2 centers

• Novartis Investigative Site — Seoul
• Novartis Investigative Site — Seoul

Spain · 2 centers

• Novartis Investigative Site — Barcelona
• Novartis Investigative Site — Madrid

Italy · 1 center

• Novartis Investigative Site — Roma

Netherlands · 1 center

• Novartis Investigative Site — Utrecht

Identifiers

NCT: NCT07354074 · CABL001I12202 · 2025-522138-29

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗