Clinical Study Protocol of Idarubicin, Cytarabine, and Venetoclax -Induced Remission Followed by Consolidation Therapy With Medium-dose Cytarabine Combined With Venetoclax in Newly Diagnosed Adult Acute Myeloid Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- The composite complete remission rate (CR+CRi)
研究概览
简要总结
This study evaluates the efficacy and safety of the combination of idarubicin and cytarabine induction followed by intermediate-dose cytarabine consolidation with venetoclax in the treatment of newly diagnosed adult acute myeloid leukemia (AML).
This study includes the induction and consolidation phases of AML treatment.
详细描述
This is a prospective, multicenter, open-label, single-arm clinical study aimed at observing and evaluating the effectiveness and safety of idarubicin and cytarabine induction followed by intermediate-dose cytarabine consolidation therapy in newly diagnosed adult AML. The results of this study will help to understand the efficacy and safety of idarubicin and cytarabine combination therapy followed by intermediate-dose cytarabine consolidation in newly diagnosed adult AML, providing guidance for clinical practice.
Acute myeloid leukemia (AML) is a heterogeneous hematopoietic stem/progenitor cell malignancy. The World Health Organization (WHO) defines AML as a myeloid tumor with primitive cells accounting for 20% or more in peripheral blood or bone marrow. It is also the most common acute leukemia in adults and the tenth leading cause of cancer-related deaths worldwide.Treatment for AML consists of induction therapy and consolidation therapy (including chemotherapy and hematopoietic stem cell transplantation (HSCT)).
The most commonly used is the 3+7 regimen. In 2018, our center conducted a retrospective analysis of 242 newly diagnosed AML patients treated with the standard IA regimen, evaluating its efficacy and adverse reactions, and conducting prognostic factor analysis. The study results showed that the CR rate of one course of IA regimen induction therapy was 81.28%; after repeated induction therapy, the CR rate reached 92.34%, confirming that the IA regimen induction therapy has a high CR rate, consistent with many literature reports.
The FDA has approved the combination therapy of Venetoclax and Decitabine/Azacitidine for elderly (>60 years old) newly diagnosed AML patients who are not eligible for intensive chemotherapy. Venetoclax, the first highly selective BCL-2 inhibitor available globally, is a BH3 mimetic that selectively binds to the BCL-2 protein, displacing and releasing pro-apoptotic proteins that were originally bound to BCL-2, effectively inducing apoptosis in tumor cells.
Currently, preclinical studies have confirmed that the combination of idarubicin and cytarabine with venetoclax has a synergistic effect in the anti-tumor treatment of AML. Based on this, the CAVEAT study included 51 newly diagnosed primary or secondary AML patients aged ≥65 years who had not previously received intensive therapy (including AML patients with monosomal karyotype aged ≥60 years). The median age of the patients was 72 years. The treatment regimen for induction and consolidation therapy included idarubicin, cytarabine, and venetoclax (with reduced intensity for idarubicin and cytarabine). The overall response rate (ORR) was 72%, and the median overall survival (OS) was 11.2 months. Compared to secondary AML, patients with primary AML had a longer median OS (31.3 months vs 6.1 months). The most common non-hematologic adverse reactions included febrile neutropenia (55%), sepsis (35%), and diarrhea (35%). These studies suggest that the combination of idarubicin, cytarabine, and venetoclax is safe and tolerable in elderly fit AML patients, and can provide higher remission rates and longer survival. The results of this study also partly confirm the safety of venetoclax in combination with cytarabine and idarubicin for induction chemotherapy in elderly AML patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Newly diagnosed primary AML patients. Diagnostic criteria refer to the 2022 WHO classification.
- •Age between 18 and 60 years old.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (see Appendix 2).
- •Cardiac ultrasound LVEF ≥ 45%.
- •Creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula or measured using a 24-hour urine sample).
- •Liver function: Aspartate aminotransferase (AST) ≤ 2.5 × ULN*; Alanine aminotransferase (ALT) ≤ 2.5 × ULN*; Total bilirubin ≤ 1.5 × ULN* (*unless considered due to leukemia infiltration).
- •Signed informed consent form.
排除标准
- •Acute promyelocytic leukemia (APL).
- •Relapsed/refractory AML patients.
- •AML patients with known involvement of the central nervous system (CNS).
- •Known HIV-infected participants (due to potential drug-drug interactions between antiretroviral drugs and venetoclax). HIV testing will be conducted during screening according to local guidelines or institutional standards.Participants with positive hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Non-active carriers of viral hepatitis or participants with low viral hepatitis viral titers after receiving non-prohibited antiviral therapy will not be excluded.
- •Participants who have received strong or moderate CYP3A inducers/inhibitors therapy within 7 days prior to starting study treatment.
- •Participants with New York Heart Association (NYHA) functional classification > Grade
- •Grade 2 is defined as patients having cardiac disease with no symptoms at rest but experiencing fatigue, palpitations, dyspnea, or angina with ordinary physical activity.
- •Participants with chronic respiratory disease requiring continuous oxygen therapy.
- •Patients unable to take oral medications or with malabsorption syndrome.
- •Presence of uncontrolled systemic infection (viral, bacterial, or fungal).
- •Participants who have previously received venetoclax treatment and/or are currently participating in any other study involving investigational drugs.
研究组 & 干预措施
Induction therapy and consolidation therapy after remission
Induction therapy:Venetoclax + idarubicin + cytarabine Consolidation therapy after remission:Venetoclax + cytarabineIf The patient meets the criteria for autologous hematopoietic stem cell transplantation (ASCT) during the treatment process, they can undergo ASCT.If the patient meets the criteria for transplantation and there is a suitable donor, they can undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT).
干预措施: utologous stem cell transplantation (ASCT) /allogeneic hematopoietic stem cell transplantation (allo-HSCT). (Other)
结局指标
主要结局
The composite complete remission rate (CR+CRi)
时间窗: Four months from the start of initial induction therapy.
Composite complete remission rate: the proportion of patients who achieve complete remission (CR) and complete remission with incomplete hematologic recovery (CRi) at the end of induction therapy (CR+CRi).• CR is defined as meeting all of the following criteria: ① bone marrow blasts \<5%, no circulating or Auer rod blasts; ② no extramedullary disease; ③ ANC ≥1.0 × 109 /L; ④ platelet count ≥100 × 109 /L.• CRi is defined as PLT ≤100 × 109 /L and/or ANC ≤1.0 × 109 /L, with other criteria for CR being met.
次要结局
- The incidence of hematological adverse reactions during induction therapy(Four months from the start of initial induction therapy.)