A Study of Treatment-free Remission in Chronic Phase Chronic Myeloid Leukemia

Phase 2

Not yet recruiting

• Conditions: Chronic Myeloid Leukemia, Chronic Phase
• Interventions: Drug: Asciminib

• Registration Number: NCT06368414
• Lead Sponsor: Korean Society of Hematology

Brief Summary

To evaluate the efficacy of asciminib adding on tyrosine-kinase inhibitors (TKI) to achieve treatment-free remission (TFR) in chronic myeloid leukemia (CML) patients in chronic phase who failed prior cessation study of TKI

Detailed Description

We expect that patients who lost MR3.0 after stopping TKIs, thus failed to maintain treatment-free remission can achieve second sustainable MR4.5 by sustainable MR4.5 for more than 3 years once regained and prolong MRFS by adding asciminib to TKIs. Patients will be restarted on TKIs when they fail sustaining MR3.0 after cessation because restarting TKIs when loss of MR3.0 is reasonable in this situation.

Study Timeline

• Status Verified: 2024-04
• Study First Submitted: 2024-04-11
• Study First Submitted QC: 2024-04-11
• Last Update Submitted: 2024-04-11
• Study First Posted: 2024-04-16
• Last Update Posted: 2024-04-16
• Study Start: 2024-09-01
• Primary Completion: 2028-08-31
• Study Completion: 2028-08-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 69

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Asciminib arm	Asciminib	-

Primary Outcome Measures

Name	Time	Method
MR3.0 or less by 1 year	by 1 year	To evaluate the cumulative incidence of sustained MR3.0 or less by 1 year of cessation of TKI and asciminib