CLAG+VEN vs CLAG in the Treatment of Relapsed/Refractory AML

Официальное название

A Multicenter, Prospective, Randomized Controlled Study Comparing the Efficacy and Safety of CLAG(Cladribine, Cytarabine and G-CSF) Combined With Venetoclax and CLAG in the Treatment of Relapsed/Refractory Acute Myeloid Leukemia

Обзор

This is a multicenter, prospective, randomized controlled clinical study comparing the efficacy and safety of CLAG+VEN and CLAG regimens in relapsed/refractory(r/r) AML.

Подробное описание

The efficacy and prognosis of relapsed/refractory(r/r) AML are very poor, and there is no standard chemotherapy regimen were defined for r/r AML. Cladribine, a purine analogue, exerts cytotoxic, proapoptotic, and antiproliferative effects on AML cells. Previous studies have confirmed the efficacy of cladribine in the treatment of r/r AML, with a response rate of 30-45%.Our previous experience has shown that CLAG in combination of venetoclax are effective with tolerable toxicity profiling. However, there is a lack of multicenter, prospective, randomized controlled trials to further confirm the results. Therefore, a clinical study is planned to evaluate the efficacy and safety of CLAG+VEN compared to CLAG in r/r AML who were eligible for intensive therapy.

Вмешательства

• Препарат Cladribine
  Given IV
• Препарат Cytarabine
  Given IV
• Препарат G-CSF
  Given SC
• Препарат Venetoclax
  Given PO

Первичные конечные точки

• Composite Complete remission (cCR, CR+CRi) [Срок оценки: At the end of Cycle 1 (each cycle is 28 days)]

Вторичные конечные точки (7)

• Overall Response rate (ORR) [Срок оценки: At the end of Cycle 1 (each cycle is 28 days)]
• MRDneg CR rate [Срок оценки: At the end of Cycle 1 (each cycle is 28 days)]
• Overall Survival(OS) [Срок оценки: 1 year post treatment]
• Relapse free survival(RFS) [Срок оценки: 1 year post treatment]
• Duration of completed response(DoR) [Срок оценки: 1 year post treatment]
• Relapse rate [Срок оценки: 1 year post treatment]
• Incidence of Adverse Events [Срок оценки: Duration of treatment, up to 1 year]

Критерии участия

Критерии включения

• Diagnosed of AML according to the World Health Organization (WHO) classification.
• All patients should aged 18 to 65 years.
• Diagnosed of relapsed and refractory AML, according to The guidelines for diagnosis and treatment of relapse /refractory acute myelogenous leukemia in China（2023）
• Diagnostic criteria for relapsed AML: Leukemia cells reappear in the peripheral blood or primitive cells in the bone marrow ≥ 5% (excluding other reasons such as bone marrow regeneration after consolidation chemotherapy) after CR, or leukemia cell infiltration appears outside the marrow.
• Diagnostic criteria for refractory AML: The newly diagnosed patients who failed to respond to two courses of standard treatment; Patients who relapsed within 12 months after consolidation intensive therapy; Patients who relapsed after 12 months and failed to respond to conventional chemotherapy; Patients with two or more recurrences; Patients with persistent extramedullary leukemia.
• The score of Eastern Cooperative Oncology Group (ECOG) is 0-2.
• Renal function: creatinine clearance rate ≥ 30ml/min.
• Liver function: ALT<5 times normal value, bilirubin<3 times normal value.
• Predicted survival ≥ 3 months.
• Able to accept oral Venetoclax.
• Sign an informed consent form and be able to understand and follow the procedures required by this protocol.

Критерии исключения

• Diagnosed of acute promyelocytic leukemia (AML-M3)
• Patients with central nervous system (CNS) invasion.
• Cardiac function < grade 2.
• Known human immunodeficiency virus (HIV) infection.
• Other clinically significant uncontrolled conditions, including but not limited to: a. uncontrolled or active systemic infections (viruses, bacteria, or fungi); b. Chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) requiring treatment; c. Secondary tumors requiring active treatment.
• Allergy to experimental drugs.
• Pregnant and lactating women.
• Patients who ineligible for the study according to the investigator's assessment.

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

• Department of Hematology,Nanfang Hospital, Southern Medical University — Гуанчжоу

Идентификаторы

NCT: NCT06763666 · NFEC-2024-639

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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