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

Chronic Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06390306
• Other study ID #: 2023PHB323-001
• Status: Not yet recruiting
• Start date: July 1, 2024
• Est. completion date: December 1, 2027

Study information

• Verified date: June 2024
• Source: Peking University People's Hospital
• Contact: Qian Jiang, MD
• Phone: +861088326006
• Email: jiangqian[@]medmail.com.cn
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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).

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 information / eligibility

• Status: Not yet recruiting
• Enrollment: 30
• Est. completion date: December 1, 2027
• Est. primary completion date: December 1, 2026
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Myeloid Leukemia
• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid

Intervention

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.
• Azacitidine
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.
• Venetoclax
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.
• Olverembatinib
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.

Locations

Country	Name	City	State
China	Peking university people's hospital	Beijing	Beijing

Sponsors (7)

Lead Sponsor	Collaborator
Peking University People's Hospital	Beijing Chuiyangliu Hospital, Henan Cancer Hospital, Nanfang Hospital, Southern Medical University, Peking Union Medical College, Wuhan Union Hospital, China, Zhejiang University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Major hematologic response (MaHR)	either a complete hematologic response (CHR) or no evidence of leukemia (NEL).	At the end of Cycle 2 (each cycle is 28 days)
Secondary	Return to chronic phase	< 10% blasts in blood and bone marrow with no extra-medullary leukemia and last for = 4 weeks	At the end of Cycle 2 (each cycle is 28 days)
Secondary	Major cytogenetic response (MCyR)	Ph-positive cells = 35%	Up to 3 years
Secondary	Complete cytogenetic response (CCyR)	no Ph-positive cell	Up to 3 years
Secondary	Major molecular response (MMR)	BCR::ABL1IS = 0.1%	Up to 3 years
Secondary	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	Up to 3 years
Secondary	CML-related survival	interval from therapy start to death from blast phase, or censored at the last follow-up	Up to 3 years
Secondary	Survival	interval from therapy start to death from any cause or censored at the last follow-up	Up to 3 years
Secondary	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.	Up to 3 years