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).
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.
Study Type
OBSERVATIONAL
Enrollment
30
Ponatinib is recommended orally (PO) daily continuously on days 1-28 in 28-day cycle. Treatment repeats every 28 days in the absence of disease progression, unacceptable toxicity or HSCT.
Azacitidine is recommended 75mg/m2 subcutaneously on days 1-7 in 28-day cycle. Treatment repeats every 28 days in the absence of disease progression, unacceptable toxicity or HSCT.
Venetoclax is recommended orally (PO) daily on days 1-14 in 28-day cycle. Treatment repeats every 28 days in the absence of disease progression, unacceptable toxicity or HSCT.
Peking university people's hospital
Beijing, Beijing Municipality, China
RECRUITINGBeijing Lu Daopei Hospital
Major hematologic response (MaHR)
either a complete hematologic response (CHR) or no evidence of leukemia (NEL).
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Return to chronic phase
\< 10% blasts in blood and bone marrow with no extra-medullary leukemia and last for ≥ 4 weeks
Time frame: At the end of Cycle 2 (each cycle is 28 days)
Major cytogenetic response (MCyR)
Ph-positive cells ≤ 35%
Time frame: Up to 3 years
Complete cytogenetic response (CCyR)
no Ph-positive cell
Time frame: Up to 3 years
Major molecular response (MMR)
BCR::ABL1IS ≤ 0.1%
Time frame: Up to 3 years
Event-free survival (EFS)
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
Time frame: Up to 3 years
CML-related survival
interval from therapy start to death from blast phase, or censored at the last follow-up
Time frame: Up to 3 years
Survival
interval from therapy start to death from any cause or censored at the last follow-up
Time frame: Up to 3 years
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Olverembatinib is recommended orally (PO) every other day on days 1-28 in 28-day cycle. Treatment repeats every 28 days in the absence of disease progression, unacceptable toxicity or HSCT.
Beijing, China
Chuiyangliu hospital affiliated to tsinghua university
Beijing, China
NOT_YET_RECRUITINGSichuan Provincial People's Hospital
Chengdu, China
NOT_YET_RECRUITINGNanfang Hospital, Southern Medical University
Guangdong, China
NOT_YET_RECRUITINGThe First Affiliated Hospital of Kunming Medical University
Kunming, China
NOT_YET_RECRUITINGThe First Affiliated Hospital of Nanjing Medical University
Nanjing, China
RECRUITINGThe First Affiliated Hospital of Guangxi Medical University
Nanning, China
RECRUITINGNanyang Central Hospital
Nanyang, China
RECRUITINGNingbo Medical Center Lihuili Hospital
Ningbo, China
RECRUITING...and 5 more locations
Incidence of adverse events
Adverse effects (AEs) were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. and assessed continuously.
Time frame: Up to 3 years