The Efficacy and Safety of Third-generation TKIs Combined With Azacitidine and Bcl-2 Inhibitor in Patients With CML-MBP

Peking University

Status: Enrolling

Conditions: Chronic Myeloid Leukemia

Treatments: Drug: Olverembatinib; Drug: Azacitidine; Drug: Venetoclax; Drug: Ponatinib

Study type: Observational

Funder types: Other

Identifiers

NCT06390306

2023PHB323-002

Details and patient eligibility

About

This is a prospective multi-center study to investigate efficacy and safety of the third generation tyrosine kinase inhibitors (TKIs) combined with azacitidine and B-cell lymphoma-2 (Bcl-2) inhibitor in patients with myeloid blast phase chronic myeloid leukemia (CML-MBP).

Full description

CML-MBP has dismal outcome. Currently, there is no standardized induction treatment approach in CML-MBP. The European LeukemiaNet (ELN) recommendations and NCCN guideline recommended the combination of TKI and chemotherapy in CML-MBP. The previous study revealed that TKI combined with hypomethylating agents had promising efficacy. However, imatinib and second generation TKI are the most widely applied in combination treatment, there is limited data in third generation TKI.

Currently, venetoclax in combination with hypomethylating agents such as azacitidine is standard treatment for patients with AML unsuitable for intensive induction chemotherapy. Maiti et al. reported that TKI combined with venetoclax and detectable had promising efficacy in CML-MBP. Therefore, the investigator conducted a study to explore the efficacy and safety of a third generation TKI in combination with azacitidine and Bcl-2 inhibitor in CML-MBP and multi-omics exploratory analysis was performed to identify potential biomarkers correlated with the outcome.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

30 participants in 1 patient group

3G-TKI + AZA + Ven group

Description:

Adult CML-MBP

Treatment:

Drug: Venetoclax

Drug: Ponatinib

Drug: Olverembatinib

Drug: Azacitidine