Third-generation TKI combined with azacitidine and a Bcl-2 inhibitor for CML in myeloid blast phase

The Efficacy and Safety of Third Generation Tyrosine Kinase Inhibitors Combined With Azacitidine and B-cell Lymphoma-2 Inhibitor in Patients With Myeloid Blast Phase Chronic Myeloid Leukemia

This study will test whether adding a third-generation TKI to azacitidine and a Bcl-2 inhibitor helps adults with Philadelphia chromosome–positive chronic myeloid leukemia in myeloid blast phase.

Quick facts

• Study type: Observational
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Peking University People's Hospital (Academic / other)
• Drugs / interventions: imatinib, chemotherapy
• Locations: 15 sites (Beijing, Beijing Municipality and 14 other locations)
• Trial ID: NCT06390306 on ClinicalTrials.gov

What this trial studies

This is a prospective, multicenter observational study enrolling adults with Philadelphia chromosome–positive CML in myeloid blast phase to receive a third-generation TKI (for example ponatinib or olverembatinib) combined with azacitidine and a Bcl-2 inhibitor (venetoclax). The protocol will collect data on safety, hematologic and molecular response rates, and survival over predefined follow-up periods. Investigators will perform exploratory multi-omics analyses on patient samples to identify biomarkers associated with response or resistance. Data are collected across several academic medical centers in China under standardized procedures.

Who should consider this trial

Good fit: Adults (≥18 years) with Philadelphia chromosome–positive or BCR::ABL–positive CML in myeloid blast phase who meet cardiac and organ-function criteria and have not undergone allogeneic HSCT are the intended participants.

Not a fit: Patients with other active primary malignancies, significant comorbidities or interacting medications, prior allogeneic stem cell transplant, or extramedullary-only disease are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this combination could increase remission rates and improve survival for adults with CML in myeloid blast phase.

How similar studies have performed: Prior studies combining TKIs with hypomethylating agents or venetoclax have reported promising responses, but evidence specifically using third-generation TKIs remains limited.

Eligibility criteria

Inclusion Criteria:

1. age ≥ 18 years old;
2. philadelphia chromosome (Ph)-positive or BCR::ABL-positive;
3. serum creatinine ≤ 1.5 × upper limit of normal (ULN) or 24h creatinine clearance ≥ 50 mL/min when serum creatinine was \> 1.5 × ULN;
4. serum total bilirubin ≤ 1.5 × ULN;
5. aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN;
6. amylase ≤ 1.5 × ULN; (7) lipase ≤ 1.5 × ULN;
7. ejection fraction \> 50%; corrected QT interval on electrocardiographic evaluation was ≤ 450 ms in men or ≤ 470 ms in women.

Exclusion Criteria:

1. concurrent diseases requiring treatment(s) with potential to interact with 3G-TKI;
2. diagnosis of other primary malignancies;
3. history of allogeneic HSCT;
4. extramedullary disease only.

Where this trial is running

Beijing, Beijing Municipality and 14 other locations

• Peking university people's hospital — Beijing, Beijing Municipality, China (Recruiting)
• Beijing Lu Daopei Hospital — Beijing, China (Recruiting)
• Chuiyangliu hospital affiliated to tsinghua university — Beijing, China (Not_yet_recruiting)
• Sichuan Provincial People's Hospital — Chengdu, China (Not_yet_recruiting)
• Nanfang Hospital, Southern Medical University — Guangdong, China (Not_yet_recruiting)
• The First Affiliated Hospital of Kunming Medical University — Kunming, China (Not_yet_recruiting)
• The First Affiliated Hospital of Nanjing Medical University — Nanjing, China (Recruiting)
• The First Affiliated Hospital of Guangxi Medical University — Nanning, China (Recruiting)
• Nanyang Central Hospital — Nanyang, China (Recruiting)
• Ningbo Medical Center Lihuili Hospital — Ningbo, China (Recruiting)
• Qilu Hospital of Shandong University — Qilu, China (Not_yet_recruiting)
• Chinese Academy of Medical Sciences & Peking Union Medical College Hospital — Tianjin, China (Not_yet_recruiting)
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Henan Cancer Hospital — Wuhan, China (Not_yet_recruiting)
• Xi'an International Medical Center Hospital — Xi'an, China (Recruiting)
• The First Affiliated Hospital, Zhejiang University School of Medicine — Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Qian Jiang, MD — Peking University People's Hospital
• Study coordinator: Qian Jiang, MD

Conditions Chronic Myeloid Leukemia