Open-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.

NCT06514534 | Recruiting Phase 2

• 2 other identifiers: CABL001AFR052024-516049-38-00
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 6

Brief Summary

The objective of this Phase II study is to assess the potential of asciminib in managing CML-CP or CML-AP in patient carrying the T315I mutation. The presence of this mutation introduces treatment difficulties due to the limited available options. The study seeks to collect additional data on the effectiveness and safety of asciminib for these patients. By determining the drug's capacity to manage the disease and enhance patients outcomes, the study is designed to fill the unmet medical need and potentially offer a new therapeutic path for patients at a treatment deadlock.

Conditions

Chronic Myeloid Leukemia (CML)

Keywords

Asciminib; ABL001; Abelson proto-oncogene (ABL1); Chronic Myelogenous Leukemia (CML); BCR::ABL1; Phase II; Tyrosine kinase inhibitor (TKI)

Outcome Measures

Primary Outcomes (1)

• Rate of BCR::ABL1 (Breakpoint Cluster Region Gene::Abelson proto-oncogene) IS (International Scale) ≤ 1% [MR2 (Molecular Response 2)]

  Evaluation of asciminib efficacy : proportion of patients with MR2 (BCR::ABL1 IS ≤1%) level of response at 12 months.

  Month 12

Secondary Outcomes (12)

• Kinetics of response: BCR::ABL1 IS (MR2, MMR, MR4.0, MR4.5, undetectable MR4.5)

  At 3, 6, 9, 12, 18 and 24 months

• Estimate response to treatment MR2 at 12 months in participants with BCR::ABL1 IS > 1% at treatment initiation or maintenance of MR2 at 12 months in participants with MR2 at treatment initiation

  At 12 months

• Time to Major Molecular Response (MMR) (for participants not in MMR at treatment initiation)

  up to 24 months

• Duration of MMR

  up to 24 months

• Time to Molecular Response 2 (MR2) (for participants not in MR2 at treatment initiation)

  up to 24 months

Study Arms (1)

Asciminib (Scemblix®)

EXPERIMENTAL

Asciminib will be administered 200 mg twice a day orally. The minimum dose is 200 mg, and maximum dose is 400 mg.

Drug: ABL001/Asciminib

Interventions

ABL001/Asciminib DRUG

The study treatment for this clinical trial is an investigational drug called asciminib, which is marketed under the brand name Scemblix®. Asciminib is a compound that is being evaluated for its efficacy and safety in the treatment of the target condition. The minimum dose of asciminib to be administered in this study is 200 mg, while the maximum dose is 400 mg. The dose is planned as 200 mg twice a day (BID). The drug will be administered orally, allowing for convenient and non-invasive administration.

Asciminib (Scemblix®)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (6)

Novartis Investigative Site

Bordeaux, 33076, France

RECRUITING

Novartis Investigative Site

Lille, 59037, France

RECRUITING

Novartis Investigative Site

Lyon, 69373, France

RECRUITING

Novartis Investigative Site

Nantes, 44093, France

RECRUITING

Novartis Investigative Site

Paris, 75475, France

RECRUITING

Novartis Investigative Site

Vandœuvre-lès-Nancy, 54511, France

RECRUITING

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

asciminib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Central Study Contacts

Novartis Pharmaceuticals

CONTACT

+41613241111; novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

novartis.email@novartis.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-arm, open-label study

Study Record Dates

• First Submitted: July 17, 2024
• First Posted: July 23, 2024
• Study Start: February 18, 2025
• Primary Completion (Estimated): February 17, 2029
• Study Completion (Estimated): February 18, 2029
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

FR (6)