A Collaboration Phase 2 Study of Venetoclax in Combination With Conventional Chemotherapy in Pediatric Patients With Acute Myeloid Leukemia

St. Jude Children's Research Hospital23 个研究点分布在 1 个国家目标入组 70 人开始时间: 2023年7月25日最近更新: 2026年9月17日

适应症

干预措施

试验速览

阶段: 2 期
状态: 招募中
发起方: St. Jude Children's Research Hospital
入组人数: 70
试验地点: 23
主要终点: Minimal residual disease (MRD)-negativity rate

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

This is a phase 2 study to test the hypothesis that venetoclax in combination with standard chemotherapy will be tolerable and active in pediatric patients with newly diagnosed acute myeloid leukemia (AML).

Primary Objectives:

Establish the tolerability adding venetoclax to standard chemotherapy in pediatric patients with AML
Estimate the proportion of patients who become minimal residual disease (MRD) negative by flow cytometry after one course of venetoclax-based induction therapy

Secondary Objectives:

- Estimate the rates of complete remission (CR), event-free survival (EFS), and overall survival (OS) in pediatric patients who receive venetoclax-based chemotherapy

详细描述

Treatment will be based on genetic characteristics and response to therapy. Venetoclax will be given with each course of therapy. Low-risk patients will receive four courses of chemotherapy and intermediate-risk patients will receive five courses. High-risk patients who do not have a suitable stem cell donor or who decline HCT will receive five courses of chemotherapy. The definition of suitable stem cell donor and the conditioning regimens used for HCT will be determined by local institutional protocols or guidelines.

Intervention:

Low Risk

Induction 1: Venetoclax orally (PO) once daily (QD) on days -2 to 11, cytarabine intravenously (IV) over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, etoposide IV over one hour QD on days 1-5, and gemtuzumab ozogamicin IV over 2 hours on day 6.

Induction 2: Venetoclax PO QD on days 1-14, cytarabine IV over 30 minutes every 12 hours on days 1-8, daunorubicin hydrochloride IV over 1 hour QD on days 1, 3, and 5, and etoposide IV over 1 hour QD on days 1-5.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 29 Days 至 21 Years（Child, Adult）
性别: All
接受健康志愿者: 否

入选标准

•Patients with preexisting conditions that may affect chemotherapy tolerance (e.g., bone marrow failure syndrome, cardiac disease, pulmonary disease, and history of significant hepatic impairment) should be discussed with study PI in detail to enable review of the medical history prior to enrollment onto AML23 study.
•Inclusion Criteria:
•Diagnosis of AML fulfilling the criteria of the WHO classification of myeloid neoplasms or < 20% marrow myeloblasts and evidence of a clonal de novo AML genetic abnormality or myeloid sarcoma or primary myelodysplastic syndrome (MDS) with ≥ 10% blasts or a complete blood count with the presence of at least 1,000 blasts/μL (e.g., a WBC count ≥ 10,000/μL with ≥ 10% blasts or a WBC count ≥ 5,000/μL with ≥ 20% blasts
•Age > 28 days and < 22 years
•No prior therapy for this malignancy except for one dose of intrathecal therapy and hydroxyurea or low-dose cytarabine (≤ 200 mg/m^2 per day for ≤ 7 days)
•Female patients of childbearing potential must have a negative pregnancy test within 2 weeks prior to enrollment
•Male and female participants of reproductive potential must agree to use an effective contraceptive method during the study and for 6 months after study treatment
•Written informed consent from the patient and/or parent/legal guardian
•Direct bilirubin ≤ 1.5 x institutional upper limit of normal

排除标准

•Patients with treatment-related AML, Down syndrome, acute promyelocytic leukemia, chronic myeloid leukemia in blast crisis, juvenile myelomonocytic leukemia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow failure syndromes are not eligible
•Uncontrolled systemic fungal, bacterial, or viral infection or significant concurrent disease that would compromise patient safety or compliance, study participation, follow up, or interpretation of study results
•Prior exposure to any dose of anthracycline or anthracenedione
•Patients may not receive strong or moderate CYP3A inducers, such as rifampin, within 3 days of enrollment
•Patients may not receive moderate or strong CYP3A inhibitors (e.g., ketoconazole, itraconazole, voriconazole, posaconazole) within 3 days of enrollment.