Observational Study on Dose Optimization of Olverembatinib in Patients With Chronic Myeloid Leukemia in Chronic or Accelerated Phase

Observational Study on Dose Optimization of Olverembatinib in Patients With Chronic Myeloid Leukemia in Chronic or Accelerated Phase

This study is a multicenter observational study aimed to investigate the efficacy and safety of olverembatinib dose reduction to 20 mg every other day (QOD) in patients with chronic myeloid leukemia (CML) in chronic phase or accelerated phase who have achieved complete cytogenetic response (CCyR) or BCR::ABL1 (IS) ≤1%. Approximately 100 cases are planned to be enrolled.Primary endpoint: Maintenance rate of CCyR or BCR::ABL1 (IS) ≤1% within 12 months.

Secondary endpoints: Cumulative major molecular response (MMR) rate, cumulative MR4 rate, cumulative MR4.5 rate, MMR loss-free survival rate, MR4 loss-free survival rate, treatment failure-free survival rate, progression-free survival rate, overall survival rate, and safety.

Data analysis will be performed using SAS version 9.4 and R version 4.1.2. The loss-free survival rates will be calculated using the Log-rank and Kaplan-Meier methods. The cumulative response achievement rates will be calculated using the Fine-Gray method. Multivariate analysis will employ COX regression to identify relevant risk factors significantly affecting time-to-event variables, with hazard ratios (HR) and confidence intervals calculated. All adverse events occurring in subjects during the clinical trial period will be observed, including abnormal clinical symptoms, vital signs, and laboratory findings, with documentation of their clinical manifestation characteristics, severity, onset time, duration, management, and prognosis, and assessment of their relationship with the study drug. The plan is to enroll 100 cases within 12-24 months, with at least 12 months of observation.

Inclusion Criteria:

1. Age ≥ 18 years.
2. Diagnosed with chronic myeloid leukemia in the chronic phase, currently receiving olverembatinib 30 mg or 40 mg every other day (QOD). The patient must have achieved and maintained at least two consecutive confirmations of complete cytogenetic response (CCyR) or BCR::ABL1 (IS) ≤ 1% prior to enrollment and has decided to switch to olverembatinib 20 mg QOD.
3. Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0 to 2.
4. Signed informed consent must be obtained prior to any study-specific procedures. If the patient is unable to sign due to their medical condition, informed consent may be provided by the legal guardian or an immediate family member.
5. Subjects must be willing and able to comply with all study procedures and the follow-up schedule.

Exclusion Criteria:

Subjects meeting any of the following criteria will be excluded from the study:

• Female patients with a positive serum β-HCG test, or who are pregnant, breastfeeding, or planning to become pregnant during the study period;

  • Uncontrolled infection at the time of enrollment; or severe complications requiring mechanical ventilatory support or presenting with hemodynamic instability; ③ Inability or unwillingness to provide signed informed consent; ④ Any condition or disease that, in the judgment of the investigator, may compromise subject safety or interfere with the evaluation of the efficacy or safety of the investigational drug.