568 Participants Needed

Asciminib vs Nilotinib for Chronic Myeloid Leukemia

(ASC4START Trial)

Recruiting at 139 trial locations
NP
Overseen ByNovartis Pharmaceuticals
Age: 18+
Sex: Any
Trial Phase: Phase 3
Sponsor: Novartis Pharmaceuticals
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Pivotal Trial (Near Approval)This treatment is in the last trial phase before FDA approval
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

The study is designed to compare the tolerability of asciminib versus nilotinib for the treatment of newly diagnosed, previously untreated patients with Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP).

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, but it mentions that you cannot take medications with a known risk of causing heart rhythm problems (Torsades de Pointes) unless they can be safely replaced 7 days before starting the study drug.

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

Research shows that Nilotinib is effective for patients with chronic myeloid leukemia, especially those who are resistant to or cannot tolerate another drug called imatinib. Studies found that many patients achieved significant improvements, with some maintaining these benefits for up to 48 months.12345

Is asciminib safe for treating chronic myeloid leukemia?

Asciminib has shown a good safety profile in clinical trials for chronic myeloid leukemia, with fewer severe side effects compared to some other treatments. Common side effects include fatigue, low platelet counts, and anemia, but serious heart-related issues were not observed.678910

Research Team

NP

Novartis Pharmaceuticals

Principal Investigator

Novartis Pharmaceuticals

Eligibility Criteria

Adults (≥18 years) newly diagnosed with Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in chronic phase can join. They must be within 3 months of diagnosis, have an ECOG performance status of 0 or 1, and proper organ function. Excluded are those previously treated for CML (except hydroxyurea/anagrelide), with certain heart conditions, severe concurrent diseases, recent major surgery, other active malignancies within the past 3 years (some exceptions apply), a history of pancreatitis or liver disease, and known HIV/HBV/HCV infections.

Inclusion Criteria

My leukemia is in the chronic phase and has been confirmed to have the Philadelphia chromosome.
My chronic myeloid leukemia matches specific criteria set in 2013.
I am fully active or can carry out light work.
See 4 more

Exclusion Criteria

I have only been treated with hydroxyurea or anagrelide for my CML.
I have a severe illness that is not under control.
I have had pancreatitis before.
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either asciminib 80 mg QD or nilotinib 300 mg BID until unacceptable toxicity, disease progression, or at the discretion of the investigator or participants

Up to approximately 4.5 years
Visits every 4 weeks initially, then every 12 weeks

Follow-up

A safety follow-up visit/call is performed approximately 30 days after the end of treatment. Participants who discontinue treatment prematurely are followed up for survival and progression

4 weeks

Long-term follow-up

Participants are monitored for survival and progression to Accelerated Phase/Blast Crisis up until the end of the study

Up to approximately 4.5 years

Treatment Details

Interventions

  • Asciminib
  • Nilotinib
Trial OverviewThe trial is testing the tolerability and effectiveness of two oral drugs: Asciminib versus Nilotinib in adults with newly diagnosed Ph+ CML-CP. Participants will receive one drug or the other to compare how well they tolerate them and how effective they are at treating their leukemia.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: AsciminibExperimental Treatment1 Intervention
Participants will receive asciminib 80 mg QD
Group II: NilotinibActive Control1 Intervention
Participants will receive nilotinib 300 mg 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

Find a Clinic Near You

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 profile image

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye profile image

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Findings from Research

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.
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, 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.
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 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.
[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]

References

Nilotinib in patients with Ph+ chronic myeloid leukemia in accelerated phase following imatinib resistance or intolerance: 24-month follow-up results. [2022]
Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study. [2022]
Tasigna for chronic and accelerated phase Philadelphia chromosome--positive chronic myelogenous leukemia resistant to or intolerant of imatinib. [2022]
Moving on up: Second-Line Agents as Initial Treatment for Newly-Diagnosed Patients with Chronic Phase CML. [2021]
Nilotinib is superior to imatinib as first-line therapy of chronic myeloid leukemia: the ENESTnd study. [2022]
Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. [2023]
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]
[Pharmacological and clinical profile of asciminib hydrochloride, a novel first-in-class tyrosine kinase inhibitor specifically targeting ABL myristoyl pocket]. [2023]
Asciminib: First Approval. [2022]
Toxicity of Asciminib in Real Clinical Practice: Analysis of Side Effects and Cross-Toxicity with Tyrosine Kinase Inhibitors. [2023]