Chronic Myeloid Leukemia
Conditions
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.
Interventions
DRUGPonatinib
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.
DRUGAzacitidine
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.
DRUGVenetoclax
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.
DRUGOlverembatinib
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.
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Henan Cancer Hospital
Zhejiang University
Peking Union Medical College
Nanfang Hospital, Southern Medical University
Beijing Chuiyangliu Hospital
Peking University People's Hospital
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Major cytogenetic response (MCyR) | Up to 3 years | Ph-positive cells ≤ 35% |
| Complete cytogenetic response (CCyR) | Up to 3 years | no Ph-positive cell |
| Major molecular response (MMR) | Up to 3 years | BCR::ABL1IS ≤ 0.1% |
| 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 |
| CML-related survival | Up to 3 years | interval from therapy start to death from blast phase, or censored at the last follow-up |
| Survival | Up to 3 years | interval from therapy start to death from any cause 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. |
| 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 |
Countries
China
Contacts
Primary ContactQian Jiang, MD
Outcome results
None listed