Asciminib for Pediatric Chronic Myeloid Leukemia

Recruiting at 55 trial locations

Overseen By Novartis Pharmaceuticals

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Novartis Pharmaceuticals

Must be taking: TKIs

Disqualifiers: T315I mutation, Cardiac abnormality, Pancreatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

44 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores asciminib as a potential treatment for children with chronic myeloid leukemia (CML) who have previously tried a tyrosine kinase inhibitor (TKI). Researchers aim to determine if asciminib, which has shown promise in adults, is equally effective for children. The trial includes two groups based on the child's body weight and age to find the appropriate dose. It suits children who have CML, have tried at least one TKI, and are experiencing limited success with their current treatment. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group of children.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, since it involves patients who have previously been treated with TKIs, you might need to discuss your current medications with the study team to ensure they don't interfere with the trial.

Is there any evidence suggesting that asciminib is likely to be safe for pediatric patients?

A previous study found that the new pediatric dose of asciminib, at 1.3 mg/kg taken twice daily, was well tolerated by children, meaning most did not experience serious side effects. Importantly, no new safety concerns emerged, which is encouraging. This dose was selected because it achieves similar levels in the body as in adults, where asciminib is already used. Research has shown it is generally safe for children, similar to its use in adults with chronic myeloid leukemia (CML). ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic myeloid leukemia?

Unlike the standard treatments for chronic myeloid leukemia (CML), such as imatinib, dasatinib, and nilotinib, which primarily target the BCR-ABL protein, asciminib offers a novel approach by targeting the ABL myristoyl pocket, a different part of the BCR-ABL protein. This unique mechanism could potentially offer a new option for patients who develop resistance to existing therapies. Additionally, asciminib's flexible dosing options, including formulations based on body weight for children and a flat dose for adults, provide a tailored approach that could improve treatment outcomes and minimize side effects. Researchers are excited about asciminib because it represents a promising advance in the treatment landscape for pediatric CML, potentially offering more effective and personalized care.

What evidence suggests that asciminib might be an effective treatment for pediatric chronic myeloid leukemia?

Research has shown that asciminib is effective and safe for individuals with chronic-phase chronic myeloid leukemia (CML) who have undergone previous treatments. This drug targets a specific part of the cancer cell that aids its growth, offering a different approach than traditional treatments. In studies with adults, asciminib has consistently demonstrated effectiveness, and these results are being applied to children since CML behaves similarly in both groups. In this trial, participants will be divided into two groups: the pediatric formulation group, where the dose is based on body weight (1.3 mg/kg BID or 2.6 mg/kg QD), and the adult formulation group, where participants will receive a flat dose of 40 mg BID. Early findings in children suggest it is well-tolerated, with no new safety concerns. ^{2 3 5 6 7}

Who Is on the Research Team?

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for pediatric patients aged 1 to <18 years with chronic myeloid leukemia who have been treated with at least one TKI. They must not be pregnant, have a history of severe liver disease or pancreatitis, and cannot plan for a stem cell transplant. Eligible participants should have stable blood counts and organ functions.

Inclusion Criteria

Participants with Ph+ CML-CP must meet specific laboratory values at the screening visit including percentages of blasts, promyelocytes, basophils, neutrophils, platelet count, absence of extramedullary leukemic involvement, prior treatment with a minimum of one TKI, failure or intolerance to the most recent TKI therapy, specific performance status, adequate renal, hepatic, pancreatic, and cardiac function, electrolyte values within normal limits, and evidence of typical BCR-ABL1 transcript [e14a2 and/or e13a2] at the time of screening

Exclusion Criteria

My chronic myeloid leukemia has returned after worsening.

I have had acute pancreatitis in the last year or have chronic pancreatitis.

I have a history of liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Determination (Part 1)

Participants receive asciminib to determine the appropriate body weight adjusted dose

52 weeks

Regular visits for PK evaluation

Cohort Expansion (Part 2 and 3)

Participants continue treatment with BID or QD regimen based on age group and safety analysis

5 years

Regular visits for safety and efficacy monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

52 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Asciminib

Trial Overview The study tests two formulations of asciminib (pediatric and adult) in young patients previously treated with tyrosine kinase inhibitors (TKIs). It aims to establish the appropriate dose for children while assessing safety by comparing responses between age groups.

How Is the Trial Designed?

Group I: Asciminib Experimental Treatment 2 Interventions

This arm consists of 2 groups: * The pediatric formulation group where the dose is based on body weight (1.3mg/kg BID or 2.6 mg/kg QD) * The adult formulation group where participants will receive a flat dose of 40mg BID

Asciminib is already approved in United States, European Union for the following indications:

Approved in United States as Scemblix for:

• Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) in adults previously treated with ≥2 tyrosine kinase inhibitors (TKIs)
• Ph+ CML in CP with the T315I mutation
• newly diagnosed Ph+ CML in CP

Approved in European Union as Scemblix for:

• Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) in adults previously treated with ≥2 tyrosine kinase inhibitors (TKIs)
• Ph+ CML in CP with the T315I mutation

Who Is Running the Clinical Trial?

Novartis Pharmaceuticals

Lead Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

Asciminib is an effective treatment for chronic myeloid leukemia (CML) in patients who have previously been treated with at least two tyrosine kinase inhibitors, showing a major molecular response (MMR) rate of 25.5% compared to 13.2% in the control group during the phase III ASCEMBL study.

While asciminib is generally effective, it can cause significant side effects, including thrombocytopenia, neutropenia, and increased pancreatic enzymes, with at least 5% of patients experiencing these adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With at Least Two Tyrosine Kinase Inhibitors. Tesileanu, CMS., Michaleas, S., Gonzalo Ruiz, R., et al.[2023]

Asciminib, a new treatment for chronic myeloid leukemia (CML), showed superior efficacy compared to bosutinib, with a major molecular response rate of 37.6% versus 15.8% after 96 weeks in patients who had previously been treated with two or more tyrosine kinase inhibitors.

Patients taking asciminib experienced fewer severe adverse events and were more likely to continue treatment without discontinuation, indicating better safety and tolerability compared to bosutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. Hochhaus, A., Réa, D., Boquimpani, C., et al.[2023]

In a phase 3 study, asciminib showed significant superiority over bosutinib in achieving major molecular response (MMR) in Japanese patients with chronic myeloid leukemia (CML) who had previously been treated with at least two tyrosine kinase inhibitors, with an MMR rate of 30.8% at week 24.

The safety profile of asciminib was comparable to that observed in the overall study population, supporting its use as an effective treatment option for Japanese patients with CML-CP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib vs bosutinib in CML patients pretreated with ≥2 tyrosine kinase inhibitors: Results from the Japanese subgroup analysis of ASCEMBL study. Yuda, J., Doki, N., Matsuoka, H., et al.[2023]

Asciminib (Scemblix®) is an innovative oral medication that selectively inhibits the BCR-ABL1 tyrosine kinase, specifically targeting the myristoyl pocket, making it effective against certain mutations like T315I that resist traditional treatments.

In October 2021, asciminib received accelerated approval for adults with Philadelphia chromosome-positive chronic myeloid leukaemia (CML) who have previously been treated with at least two other tyrosine kinase inhibitors, highlighting its efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib: First Approval. Deeks, ED.[2022]

Asciminib is the first drug that specifically targets the ABL myristoyl pocket, showing promising efficacy and safety in patients with chronic myeloid leukemia (CML) who have previously been treated with multiple tyrosine kinase inhibitors (TKIs).

The ongoing phase III trial (ASC4FIRST) is comparing asciminib to standard TKIs in newly diagnosed CML patients, with the primary goal of achieving a major molecular response by week 48, highlighting its potential as a new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. Cortes, JE., Hochhaus, A., Takahashi, N., et al.[2023]

Asciminib hydrochloride, the first tyrosine kinase inhibitor targeting the ABL myristoyl pocket, was approved for chronic myeloid leukemia (CML) patients who are resistant or intolerant to prior therapies, showing significant antitumor effects in both lab and animal studies.

In a phase III study, asciminib demonstrated superior efficacy compared to bosutinib in achieving a major molecular response at week 24 for patients with chronic phase CML previously treated with multiple TKIs, with the most common side effect being thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of asciminib hydrochloride, a novel first-in-class tyrosine kinase inhibitor specifically targeting ABL myristoyl pocket]. Chung, J., Ariyoshi, T., Yoneda, T., et al.[2023]

In a phase 1 trial involving 115 patients with chronic myeloid leukemia (CML-CP), asciminib demonstrated long-term efficacy, with 61.3% of patients achieving a major molecular response (MMR) after approximately 4 years of treatment.

While asciminib was generally well-tolerated, common grade ≥3 adverse events included increased pancreatic enzymes (22.6%) and thrombocytopenia (13.9%), but most adverse events occurred in the first year, indicating a manageable safety profile over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results. Mauro, MJ., Hughes, TP., Kim, DW., et al.[2023]

Asciminib, a new treatment for chronic myeloid leukemia (CML), shows a good safety profile with a lower rate of adverse effects compared to previous tyrosine kinase inhibitors (TKIs), with 55% of patients reporting side effects and only 18% experiencing severe effects.

Despite its unique mechanism of action, asciminib does carry a risk of cross-toxicity with traditional TKIs, particularly for side effects like thrombocytopenia and anemia, indicating careful monitoring is still necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors. Pérez-Lamas, L., Luna, A., Boque, C., et al.[2023]

Asciminib is a newly FDA-approved treatment for chronic myelogenous leukemia (CML) that specifically targets the myristoyl pocket of the BCR-Abl fusion protein, effectively reducing its kinase activity.

This drug is particularly important for patients with the T315I mutation and is used as a third-line treatment, showcasing its role in managing resistant forms of CML alongside other established therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting BCR-Abl in the treatment of Philadelphia-chromosome positive chronic myelogenous leukemia. Roskoski, R.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.10027

New pediatric formulation of asciminib in children with ... Conclusions: The confirmed PF ASC dose of 1.3 mg/kg BID was well tolerated in pediatric pts, with evidence of efficacy and no new safety signals ...

2. hematologyadvisor.com hematologyadvisor.com/reports/asciminib-chronic-myeloid-leukemia-cml-optimal-dose-treatment-risk/

Study Determines Optimal Dose of Asciminib in Children ... The optimal pediatric dose was confirmed to be 1.3 mg/kg BID, which was based on asciminid exposure in pediatric participants comparable to that in adults.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2400858

Asciminib in Newly Diagnosed Chronic Myeloid Leukemia Asciminib was associated with durable, long-term efficacy and safety in previously treated patients with chronic-phase CML in the ASCEMBL trial ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11981358/

A new chapter in CML treatment: the promise of asciminib While asciminib shows promise as a second-line or even frontline therapy, long-term data on its durability, adverse effects, and potential drug ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04925479

NCT04925479 | Study to Determine the Dose and Safety of ... The aim of this study is to support development of asciminib in the pediatric population (1 to <18 years) previously treated with one or more TKIs.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6562

Interim results from the ASC4KIDS study. The phase Ib/II ASC4KIDS study (NCT04925479) aims to characterize the pharmacokinetics (PK) and long-term safety profile of ASC in pediatric pts.

7. cincinnatichildrens.org cincinnatichildrens.org/service/c/clinical-trials/studies/CABL001I12201-011724

CABL001I12201: Study to Determine the Dose and Safety ... The aim of this study is to support development of asciminib in the pediatric population (1 to <18 years) previously treated with one or more TKIs.