Treatment-free remission with asciminib plus TKIs in chronic-phase chronic myeloid leukemia

A Study of Treatment-free Remission in Chronic Phase Chronic Myeloid Leukemia in Combination With Asciminib and Tyrosine Kinase Inhibitors

This trial tests whether adding asciminib to ongoing TKI therapy helps people with chronic-phase CML who lost remission after stopping TKIs regain and sustain a deeper molecular response so they can attempt stopping treatment again.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 69 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: Korean Society of Hematology (Research network)
• Drugs / interventions: imatinib, nilotinib, dasatinib, asciminib, CAR-T, Chimeric antigen receptor
• Locations: 1 site (Incheon, Incheon)
• Trial ID: NCT06368414 on ClinicalTrials.gov

What this trial studies

This Phase 2 interventional protocol adds asciminib to patients' current TKI (imatinib, nilotinib, or dasatinib) for people with chronic-phase CML who previously failed a TKI cessation attempt. Eligible adults have been on a TKI for five years or more, lost MR3.0 after stopping TKIs, and then regained at least MR3.0 on a TKI retrial of at least 12 weeks with adequate organ function. Participants receive asciminib added to their TKI with the goal of achieving and maintaining MR4.5 for the protocol-specified duration before attempting treatment-free remission again, and TKIs will be restarted if MR3.0 is lost. The study is conducted at Gachon University Gil Medical Center in Incheon, South Korea, and is sponsored by the Korean Society of Hematology.

Who should consider this trial

Good fit: Ideal candidates are adults with chronic-phase CML who have been on imatinib, nilotinib, or dasatinib for at least five years, previously failed a TKI cessation but regained MR3.0 on retreatment (with ≥12 weeks on retrial), and meet protocol organ function requirements.

Not a fit: Patients who never achieved MR3.0, have inadequate liver, kidney, or pancreatic function, or are unwilling to follow the protocol-required stopping plan are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, adding asciminib could help patients who previously lost TFR re-achieve and sustain deeper molecular responses and increase the chance of staying off TKIs.

How similar studies have performed: Prior TKI cessation studies have demonstrated durable treatment-free remission for some patients, but adding asciminib to TKIs to re-induce and prolong deep molecular responses after cessation failure is a relatively new approach with limited published data.

Eligibility criteria

Inclusion Criteria:

1. 19 year or older
2. CP-CML patients who are taking current TKIs (imatinib, nilotinib or dasatinib) for 5 years or more
3. Patients who have failed maintaining MR3.0 after 1 or more cessation trial of TKIs.
4. Patients who regained MR3.0 or deeper molecular response by TKIs retrial after TKI cessation failure at the time of screening
5. Taking TKIs over 12 weeks for the retrial of TKIs after TKI cessation failure
6. Patients who agree with stopping asciminib and TKIs after maintaining 23 year-duration of MR4.5
7. Adequate end organ function as defined by:

   * Total bilirubin (TBL) \< 3 x upper limit of normal (ULN); patients with Gilbert's syndrome may only be included if TBL ≤ 3.0 x ULN or direct bilirubin ≤ 1.5 x ULN
   * Creatinine clearance (ClCr) ≥ 30 mL/min as calculated using Cockcroft-Gault formula
   * Serum lipase ≤ 1.5 x ULN. For serum lipase \> ULN - ≤ 1.5 x ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis
8. Patients who can sign the informed consent of their own free will

Exclusion Criteria:

1. Patients who experienced grade 3 or higher adverse events with TKIs (imatinib, dasatinib, and nilotinib).
2. Patients who are receiving any other investigational agents.
3. Patients who currently have uncontrolled infections
4. Patients who previously received Chimeric antigen receptor T-cell (CAR-T cell) therapy, allogeneic hematopoietic stem cell transplantation (allo-HSCT) or biologic therapy.
5. Patients with clinically significant cardiovascular disease or gastrointestinal dysfunction.
6. Patients who have a history of thromboembolic episodes within 3 months prior to the study enrollment.
7. Patients with active hepatitis B or C with uncontrolled disease activity.
8. Patients who have active malignancies requiring treatment other than CML.
9. Patients with any severe and/or uncontrolled medical conditions or other conditions that could adversely impact on patients' ability to participate in the study.
10. Patients with psychiatric illness/social situations that would limit compliance with study requirements.
11. Pregnant women are excluded from this study Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with asciminib and TKIs, breastfeeding should be discontinued if the mother is treated with asciminib and TKIs.

Where this trial is running

Incheon, Incheon

• Gachon University Gil Medical Center — Incheon, Incheon, South Korea (Recruiting)

Study contacts

• Study coordinator: Hawk Kim

Conditions Chronic Myeloid Leukemia, Chronic Phase