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

Study Purpose

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).

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	Unknown
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Observational [Patient Registry]
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion 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.

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT06390306
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Peking University People's Hospital
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Qian Jiang, MD
Principal Investigator Affiliation	Peking University People's Hospital
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Other
Overall Status	Not yet recruiting
Countries	China
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Chronic Myeloid Leukemia

Additional Details

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.

Arms & Interventions

Arms

: 3G-TKI + AZA + Ven group

Adult CML-MBP

Interventions

Drug: - Ponatinib

CML-MBP receive ponatinib or olverembatinib daily combined with venetoclax ( 2 weeks) and azacitidine (D1-D7) in 28-day cycles. Subjects receive allogeneic HSCT after returning to chronic phase if applicable, whereas continuing the regimen until loss of response.

Drug: - Azacitidine

Drug: - Venetoclax

Drug: - Olverembatinib

Contact a Trial Team

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International Sites

Peking university people's hospital, Beijing, Beijing, China

Status

Address

Peking university people's hospital

Beijing, Beijing, 100044

Site Contact

Cuicui Cong Peking university people's hospital

[email protected]

+861088324516

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