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Recruiting NCT06390306

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

— Observational Chronic Myeloid Leukemia

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Ponatinib, Azacitidine, Venetoclax, Olverembatinib.
Who it may be relevant to
Registry conditions: Chronic Myeloid Leukemia. Basic parameters: from 18 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
China
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

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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

Overview

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

  • Drug Ponatinib
    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.
  • Drug Azacitidine
    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.
  • Drug Venetoclax
    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.
  • Drug Olverembatinib
    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.

Primary outcome measures

  • Major hematologic response (MaHR) [Time frame: At the end of Cycle 2 (each cycle is 28 days)]
Secondary outcome measures (8)
  • Return to chronic phase [Time frame: At the end of Cycle 2 (each cycle is 28 days)]
  • Major cytogenetic response (MCyR) [Time frame: Up to 3 years]
  • Complete cytogenetic response (CCyR) [Time frame: Up to 3 years]
  • Major molecular response (MMR) [Time frame: Up to 3 years]
  • Event-free survival (EFS) [Time frame: Up to 3 years]
  • CML-related survival [Time frame: Up to 3 years]
  • Survival [Time frame: Up to 3 years]
  • Incidence of adverse events [Time frame: Up to 3 years]

Eligibility criteria

Inclusion criteria

  • age ≥ 18 years old;
  • philadelphia chromosome (Ph)-positive or BCR::ABL-positive;
  • serum creatinine ≤ 1.5 × upper limit of normal (ULN) or 24h creatinine clearance ≥ 50 mL/min when serum creatinine was \> 1.5 × ULN;
  • serum total bilirubin ≤ 1.5 × ULN;
  • aspartate aminotransferase and alanine aminotransferase ≤ 2.5 × ULN;
  • amylase ≤ 1.5 × ULN; (7) lipase ≤ 1.5 × ULN;
  • ejection fraction \> 50%; corrected QT interval on electrocardiographic evaluation was ≤ 450 ms in men or ≤ 470 ms in women.

Exclusion criteria

  • concurrent diseases requiring treatment(s) with potential to interact with 3G-TKI;
  • diagnosis of other primary malignancies;
  • history of allogeneic HSCT;
  • extramedullary disease only.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Study design

Observational model
Cohort

Study locations

China · 15 centers
  • Peking university people's hospital — Beijing
  • Beijing Lu Daopei Hospital — Beijing
  • Chuiyangliu hospital affiliated to tsinghua university — Beijing
  • Sichuan Provincial People's Hospital — Chengdu
  • Nanfang Hospital, Southern Medical University — Guangdong
  • The First Affiliated Hospital of Kunming Medical University — Kunming
  • The First Affiliated Hospital of Nanjing Medical University — Nanjing
  • The First Affiliated Hospital of Guangxi Medical University — Nanning
  • … and 7 more centers

Identifiers

NCT: NCT06390306 · 2023PHB323-002

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗