Using asciminib to treat chronic myeloid leukemia patients with a specific mutation

A Phase II, Multi-center, Prospective, Open-label Study of Asciminib in Patients With Chronic Myeloid Leukemia in Chronic Phase (CML-CP) or Accelerated Phase (CML-AP) With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.

This study is testing if a new drug called asciminib can help people with chronic myeloid leukemia who have a specific mutation and haven't had success with other treatments.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Novartis (Industry-sponsored)
• Drugs / interventions: ponatinib, asciminib
• Locations: 6 sites (Bordeaux and 5 other locations)
• Trial ID: NCT06514534 on ClinicalTrials.gov

What this trial studies

This Phase II, multi-center, open-label study evaluates the efficacy and safety of asciminib in patients with chronic myeloid leukemia (CML) who have the T315I mutation and are resistant, intolerant, or ineligible for ponatinib. Participants will be enrolled if they have not previously received asciminib and have documented resistance or intolerance to at least one tyrosine kinase inhibitor. The study consists of a core phase to assess the drug's effectiveness and safety, followed by an extension phase allowing continued treatment if the drug is commercialized. The goal is to provide a new therapeutic option for patients facing limited treatment choices.

Who should consider this trial

Good fit: Ideal candidates are adults with chronic myeloid leukemia who have the T315I mutation and have experienced resistance or intolerance to ponatinib.

Not a fit: Patients who have previously received asciminib or have undergone hematopoietic allogeneic stem-cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could offer a new treatment option for patients with CML who have limited alternatives due to the T315I mutation.

How similar studies have performed: While studies on asciminib have shown promise, this specific approach targeting the T315I mutation in CML is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Signed informed consent must be obtained prior to participation in the study.
* Male or female participants with a diagnosis of CML-CP or CML-AP ≥ 18 years of age.
* Patients with CML-CP or CML-AP with history of documented T315I mutation after at least one TKI and are resistant, intolerant, or ineligible to ponatinib (according to Investigator judgment)
* Not already treated with asciminib or another any allosteric TKI
* Failure (adapted from the 2020 \& 2013 ELN Guidelines) or intolerance to Ponatinib at the time of Screening.
* Ineligible to ponatinib according to Investigator (based on EU ponatinib SmPC)
* Evidence of typical BCR::ABL1 transcript or atypical transcripts at the time of Screening which are amenable to standardized or non-standardized RQ-PCR quantification.

Exclusion Criteria:

* Previous hematopoietic allogeneic stem-cell transplantation
* Cardiac or cardiac repolarization abnormality
* Severe and/or uncontrolled concurrent medical disease that in the opinion of the Investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection, pulmonary hypertension)
* History of clinical acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis (except if ponatinib-induced and completely resolved at time of Screening)
* History of acute or chronic liver disease (i.e., cirrhosis; liver impairment)
* Known presence of significant congenital or acquired bleeding disorder unrelated to cancer
* History of other active malignancy within 3 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively
* Known history of Human Immunodeficiency Virus (HIV), chronic Hepatitis B Virus (HBV), or chronic Hepatitis C Virus (HCV) infection. Testing for Hepatitis B surface antigen (HBs Ag) and Hepatitis B core antibody (HBcAb / anti HBc) will be performed at Screening
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
* Treatment with medications that meet one of the following criteria and that cannot be discontinued at least one week prior to the start of treatment with study treatment:

  * Moderate or strong inducers of CYP3A
  * Moderate or strong inhibitors of CYP3A
* Pregnant or nursing (lactating) women
* Women of child-bearing potential
* Compound mutant T315I resistant to asciminib monotherapy (polyclonal ABL1 mutations including T315I can be enrolled) Other protocol-defined inclusion/exclusion criteria may apply.

Where this trial is running

Bordeaux and 5 other locations

• Novartis Investigative Site — Bordeaux, France (Recruiting)
• Novartis Investigative Site — Lille, France (Recruiting)
• Novartis Investigative Site — Lyon, France (Recruiting)
• Novartis Investigative Site — Nantes, France (Recruiting)
• Novartis Investigative Site — Paris, France (Recruiting)
• Novartis Investigative Site — Vandœuvre-lès-Nancy, France (Recruiting)

Study contacts

• Study coordinator: Novartis Pharmaceuticals

Conditions Chronic Myeloid Leukemia; Asciminib; ABL001; Abelson proto-oncogene; Chronic Myelogenous Leukemia; BCR::ABL1; Phase II; Tyrosine kinase inhibitor