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

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

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

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Myeloid Leukemia, Chronic Phase
• Intervention / Treatment: Drug: Asciminib

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 Type: Interventional
• Enrollment (Estimated): 69
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hawk Kim; Phone Number: 82-10-8533-8019; Email: ksh.cml.wp@gmail.com
• Study Contact Backup: Name: Eunju Park; Phone Number: 82-10-8533-8019; Email: ksh.cmlwp.cra1@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Asciminib arm

Drug: Asciminib; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MR3.0 or less by 1 year	To evaluate the cumulative incidence of sustained MR3.0 or less by 1 year of cessation of TKI and asciminib	by 1 year

Collaborators and Investigators

• Sponsor: Korean Society of Hematology
• Investigators: Study Chair: Hawk Kim, Korean Society of Hematology

Publications and helpful links

General Publications

• Levey AS, Coresh J, Greene T, Stevens LA, Zhang YL, Hendriksen S, Kusek JW, Van Lente F; Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006 Aug 15;145(4):247-54. doi: 10.7326/0003-4819-145-4-200608150-00004. Erratum In: Ann Intern Med. 2008 Oct 7;149(7):519. Ann Intern Med. 2021 Apr;174(4):584.

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: April 11, 2024
• First Submitted That Met QC Criteria: April 11, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Chronic Disease; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Asciminib
• Other Study ID Numbers: KCMLWP-2021-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No