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

Официальное название

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

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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.
• Препарат 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.
• Препарат 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.

Первичные конечные точки

• Major hematologic response (MaHR) [Срок оценки: At the end of Cycle 2 (each cycle is 28 days)]

Вторичные конечные точки (8)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 15 центров

• Peking university people's hospital — Пекин
• Beijing Lu Daopei Hospital — Пекин
• Chuiyangliu hospital affiliated to tsinghua university — Пекин
• Sichuan Provincial People's Hospital — Чэнду
• Nanfang Hospital, Southern Medical University — Guangdong
• The First Affiliated Hospital of Kunming Medical University — Куньмин
• The First Affiliated Hospital of Nanjing Medical University — Нанкин
• The First Affiliated Hospital of Guangxi Medical University — Nanning
• … и ещё 7 центров

Идентификаторы

NCT: NCT06390306 · 2023PHB323-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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