Clinical Study of Venetoclax Combined With CACAG Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Официальное название

A Prospective,Randomized,and Comparative Study on the Efficacy of Venetoclax Combined With CACAG Regimen and BAT Regimen in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Обзор

The purpose of this study is to compare the efficacy and safety of venetoclax combined with CACAG regimen with BAT regimen in the treatment of relapsed/refractory acute myeloid leukemia.

Подробное описание

Despite advances in therapies for acute myeloid leukemia (AML) in the past decades, some patients still suffer from relapsed/refractory (R/R) disease, resulting in poor outcomes. With a median overall survival (OS) of 4-7 months under classic chemotherapy approaches, it is imperative to explore new treatment options.Accumulating research has demonstrated the importance of epigenetic modification in the pathogenesis of chemoresistance. Recent studies have shown that combining venetoclax with hypomethylating agents (HMAs) such as azacitidine, or low-dose cytarabine (LDAC) improves the response and survival rates in R/R AML patients. To enhance the response rate, we designed a regimen that combines chidamide, azacitidine, cytarabine, aclarubicin, and G-CSF with venetoclax (CACAG+VEN regimen) for the treatment of patients with R/R AML. In this study, we intend to compare the efficacy and safety of venetoclax combined with the CACAG regimen with Best-Available Therapy(BAT) regimen in the treatment of relapsed/refractory acute myeloid leukemia.

Вмешательства

• Препарат Azacytidine;Cytarabine;Aclacinomycin;Chidamide;Venetoclax;Granulocyte colony-stimulating factor
  1. Azacytidine (75mg/m2/day, days 1 to 7). 2. Cytarabine (75-100mg/m2 q12h, days 1 to 5). 3. Aclacinomycin(20mg/day, days 1,3,5). 4. Chidamide(30mg/day , days 1,4,8,11). 5. Venetoclax (100mg on day 1,200mg on day 2,400mg on days 3-14). 6. Granulocyte colony stimulating factor (300 μg/day, day 0 until agranulocytosis recovery)
• Препарат Best-Available Therapy(BAT) Regimen
  1. FLAG regimen:Fludarabine(30mg/m2,days 1-5)+Cytarabine (1-2g/m2 applied 4h after fludarabine, days 1 to 5)+Granulocyte colony-stimulating factor(300ug/day,days 0 to 5) 2. CLAG regimen:Cladribine(5mg/2,days 1-5)+Cytarabine (1-2g/m2 applied 4h after fludarabine, days 1 to 5)+Granulocyte colony-stimulating factor(300ug/day,days 0 to 5) 3. MAE regimen:Mitox(10mg/m2,days 1 to 5)+VP-16(100mg/m2,days 1 to 5)+Cytarabine (100-150mg/m2,days 1 to 7) 4. DCAG regimen:Decitabine(20mg/m2,days 1 to 5)+Aclacin

Первичные конечные точки

• Overall Response Rate (ORR) after 1 course of treatment [Срок оценки: 1 months after the start of study treatment]

Вторичные конечные точки (9)

• Complete Remission (CR) Rate after 1 course of treatment [Срок оценки: 2 months after study treatment]
• Complete Remission (CR) Rate after 2 courses of treatment [Срок оценки: After two courses of chemotherapy (each course is 28 days)]
• Overall Response Rate (ORR) after 2 course of treatment [Срок оценки: After two courses of chemotherapy (each course is 28 days)]
• Rate of Minimal Residual Disease (MRD)-Negative Response [Срок оценки: After two courses of chemotherapy (each course is 28 days)]
• Event-free survival [Срок оценки: 180 days after study treatment]
• Overall Survival (OS) [Срок оценки: 180 days after study treatment]
• Treatment-related adverse events [Срок оценки: From the first dose of study treatment to 30 days after the discontinuation of treatment]
• Early death [Срок оценки: Within 30 days of the start of the first course of treatment]
• Disease-free survival [Срок оценки: 180 days after study treatment]

Критерии участия

Критерии включения

• Patients who are able to understand and willing to sign the informed consent form (ICF).
• All patients should aged 14 to 75 years,no gender limitation.
• Patients with R/R AML, diagnosed in accordance with the 2021 edition of the CMA criteria
• Liver function: ALT and AST≤2.5 times the upper limit of normal ,bilirubin≤2 times the upper limit of normal;
• Renal function: creatinine ≤the upper limit of normal;
• Patients without any uncontrolled infections , without organ dysfunction or without severe mental illness;
• The score of Eastern Cooperative Oncology Group (ECOG) is 0-3,and the predicted survival ≥ 4 months.
• Patients without severe allergic constitution.

Критерии исключения

• Patients with allergy or contraindication to the study drug;
• Female patients who are pregnant or breast-feeding.
• Patients with a known history of alcohol or drug addiction on the basis that there could be a higher risk of non-compliance to study treatment;
• Patients with mental illness or other states unable to comply with the protocol;
• Less than 6 weeks after surgical operation of important organs.
• Liver function: ALT and AST>2.5 times the upper limit of normal ,bilirubin>2 times the upper limit of normal;Renal function: creatinine >the upper limit of normal;
• The patient is not suitable for this clinical trial (poor compliance, substance abuse, etc.)

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Chinese PLA General Hospital — Пекин

Идентификаторы

NCT: NCT06084819 · S2023-413-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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