Asciminib for Pediatric Chronic Myeloid Leukemia

Recruiting at 48 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

34 Participants Needed

Trial Summary

What is the purpose of this trial?

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. Full extrapolation of the efficacy of asciminib from adult to pediatric patients will be conducted. Full extrapolation is based on the concept that CML in the pediatric population has the same pathogenesis, similar clinical characteristics and progression pattern as in adults.

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.

What data supports the effectiveness of the drug Asciminib for treating pediatric chronic myeloid leukemia?

Asciminib has shown effectiveness in treating adults with chronic myeloid leukemia (CML) who have not responded to other treatments, with studies showing it works better and has fewer side effects than another drug called bosutinib. It targets a specific part of the cancer-causing protein, making it a promising option for patients with certain mutations. ^{1 2 3 4 5}

Is asciminib safe for use in humans?

Asciminib has been studied in various clinical trials and is generally considered to have a good safety profile. Common side effects include fatigue, low platelet counts (thrombocytopenia), and low white blood cell counts (neutropenia). Serious side effects like increased pancreatic enzymes and high blood pressure (hypertension) have been reported but are less common. ^{1 2 4 6 7}

How is the drug Asciminib unique for treating pediatric chronic myeloid leukemia?

Asciminib is unique because it is the first drug to specifically target the ABL myristoyl pocket of the BCR-ABL1 protein, making it effective against certain mutations that cause resistance to other treatments. It is taken orally and has shown better efficacy and safety compared to some existing treatments for chronic myeloid leukemia. ^{1 2 3 8 9}

Research Team

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

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

Male or female participants in the Pediatric formulation group must be ≥ 1 and less than 18 years of age at study entry. Male or female participants in the Adult formulation group must be ≥ 14 and less than 18 years of age with a body weight of ≥ 40 kg at study entry

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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, 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]

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]

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]

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 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]

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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Asciminib: First Approval. [2022]

2. England 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. [2023]

4. Japan 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]. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

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

6. England 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. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors. [2023]

8. England 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. [2023]

9. United States 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. [2023]