Clinical trial NCT06390306: The Efficacy and Safety of Third-generation TKIs Combined With Azacitidine and Bcl-2 Inhibitor in Patients With CML-MBP
Official title: The Efficacy and Safety of Third Generation Tyrosine Kinase Inhibitors Combined With Azacitidine and B-cell Lymphoma-2 Inhibitor in Patients With Myeloid Blast Phase Chronic Myeloid Leukemia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Chronic Myeloid Leukemia
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
Collaborators: name: Wuhan Union Hospital, China
name: Henan Cancer Hospital
name: Zhejiang University
name: Peking Union Medical College
name: Nanfang Hospital, Southern Medical University
name: Beijing Chuiyangliu Hospital
First posted: 2024-04-30
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Peking universuty people's hospital Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Henan Cancer Hospital The First Affiliated Hospital, Zhejiang University School of Medicine Chinese Academy of Medical Sciences \& Peking Union Medical College Hospital Nanfang Hospital, Southern Medical University Chuiyangliu hospital affiliated to tsinghua university The First Affiliated Hospital of Nanjing Medical University Qilu Hospital of Shandong University Xi'an International Medical Center Hospital Nanyang Central Hospital Ningbo Medical Center Lihuili Hospital Beijing Lu Daopei Hospital Sichuan Provincial People's Hospital The First Affiliated Hospital of Kunming Medical University The First Affiliated Hospital of Guangxi Medical University

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.

Eligibility 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 \&gt; 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 \&gt; 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.

Primary outcomes:
measure: Major hematologic response (MaHR)
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
Secondary outcomes:
measure: Return to chronic phase
timeFrame: At the end of Cycle 2 (each cycle is 28 days)
measure: Major cytogenetic response (MCyR)
timeFrame: Up to 3 years
measure: Complete cytogenetic response (CCyR)
timeFrame: Up to 3 years
measure: Major molecular response (MMR)
timeFrame: Up to 3 years
measure: Event-free survival (EFS)
timeFrame: Up to 3 years
measure: CML-related survival
timeFrame: Up to 3 years
measure: Survival
timeFrame: Up to 3 years
measure: Incidence of adverse events
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking university people's hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Lu Daopei Hospital
city: Beijing
country: China
facility: Chuiyangliu hospital affiliated to tsinghua university
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
city: Guangdong
country: China
facility: Nanfang Hospital, Southern Medical University
city: Kunming
country: China
facility: The First Affiliated Hospital of Kunming Medical University
city: Nanjing
country: China
facility: The First Affiliated Hospital of Nanjing Medical University
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
city: Nanyang
country: China
facility: Nanyang Central Hospital
city: Ningbo
country: China
facility: Ningbo Medical Center Lihuili Hospital
city: Qilu
country: China
facility: Qilu Hospital of Shandong University
city: Tianjin
country: China
facility: Chinese Academy of Medical Sciences & Peking Union Medical College Hospital
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Henan Cancer Hospital
city: Xi'an
country: China
facility: Xi'an International Medical Center Hospital
city: Zhejiang
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
Study officials:
affiliation: Peking University People's Hospital
name: Qian Jiang, MD
role: PRINCIPAL_INVESTIGATOR
References: