The Efficacy and Safety of Third-generation TKIs Combined With Azacitidine and Bcl-2 Inhibitor in Patients With CML-MBP
- Conditions
- Chronic Myeloid Leukemia
- Interventions
- Registration Number
- NCT06390306
- Lead Sponsor
- Peking University People's Hospital
- Brief Summary
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).
- Detailed 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.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 30
- age ≥ 18 years old;
- philadelphia chromosome (Ph)-positive or BCR::ABL-positive;
- serum creatinine ≤ 1.5 × upper limit of normal (ULN) or 24h creatinine clearance ≥ 50 mL/min when serum creatinine was > 1.5 × ULN;
- serum total bilirubin ≤ 1.5 × ULN;
- aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN;
- amylase ≤ 1.5 × ULN; (7) lipase ≤ 1.5 × ULN;
- ejection fraction > 50%; corrected QT interval on electrocardiographic evaluation was ≤ 450 ms in men or ≤ 470 ms in women.
- concurrent diseases requiring treatment(s) with potential to interact with 3G-TKI;
- diagnosis of other primary malignancies;
- history of allogeneic HSCT;
- extramedullary disease only.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description 3G-TKI + AZA + Ven group Ponatinib Adult CML-MBP 3G-TKI + AZA + Ven group Venetoclax Adult CML-MBP 3G-TKI + AZA + Ven group Azacitidine Adult CML-MBP 3G-TKI + AZA + Ven group Olverembatinib Adult CML-MBP
- Primary Outcome Measures
Name Time Method Major hematologic response (MaHR) At the end of Cycle 2 (each cycle is 28 days) either a complete hematologic response (CHR) or no evidence of leukemia (NEL).
- Secondary Outcome Measures
Name Time Method Return to chronic phase At the end of Cycle 2 (each cycle is 28 days) \< 10% blasts in blood and bone marrow with no extra-medullary leukemia and last for ≥ 4 weeks
Survival Up to 3 years interval from therapy start to death from any cause or censored at the last follow-up
Major cytogenetic response (MCyR) Up to 3 years Ph-positive cells ≤ 35%
Major molecular response (MMR) Up to 3 years BCR::ABL1IS ≤ 0.1%
Event-free survival (EFS) Up to 3 years interval from therapy start to lacking RCP after 1 cycle, MaHR after 2 cycles, loss of hematologic response, progression to blast phase again, or death from any causes
CML-related survival Up to 3 years interval from therapy start to death from blast phase, or censored at the last follow-up
Incidence of adverse events Up to 3 years Adverse effects (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. and assessed continuously.
Complete cytogenetic response (CCyR) Up to 3 years no Ph-positive cell
Trial Locations
- Locations (1)
Peking university people's hospital
🇨🇳Beijing, Beijing, China