Umbilical Cord Blood Consolidation for Older Adults With Intermediate- and High-Risk AML
A Prospective, Multicenter, Randomized-Controlled Study of Cord Blood Consolidation Therapy for Intermediate- and High-Risk Elderly Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is a serious blood cancer that commonly affects older adults. Although patients may achieve complete remission after initial treatment, relapse remains common, especially in patients with intermediate- or adverse-risk disease.
This prospective, multicenter, randomized, open-label study will evaluate whether umbilical cord blood infusion used as consolidation therapy can improve outcomes in older patients with AML who have achieved complete remission after induction therapy. The study will enroll approximately 132 patients aged 60 to 80 years with newly diagnosed AML classified as intermediate or adverse risk according to the 2022 European LeukemiaNet criteria. Patients with acute promyelocytic leukemia, TP53 mutations, complex karyotypes, relapsed or refractory AML, or other conditions specified in the eligibility criteria will be excluded.
Participants will be randomly assigned in a 2:1 ratio to an experimental group or a control group. Participants in the experimental group will receive two cycles of consolidation treatment with decitabine, intermediate-dose cytarabine, and unrelated umbilical cord blood infusion. After completion of the two cord blood infusions, maintenance treatment with azacitidine will be recommended for up to 12 months. Participants in the control group will receive two cycles of standard consolidation chemotherapy with intermediate-dose cytarabine, followed by the same recommended azacitidine maintenance treatment.
Participants will be followed during maintenance treatment and for up to 2 years after consolidation therapy, or until disease progression, relapse, death, or another study endpoint occurs. The primary outcome is the proportion of participants who remain alive without leukemia relapse or additional anti-leukemia treatment at 2 years. Secondary outcomes include overall survival, conversion of measurable residual disease to negative status and duration of negativity, recovery of neutrophil and platelet counts, treatment-related mortality, and blood-related and non-blood-related toxicities. Exploratory outcomes include donor cell chimerism, immune status, and, where available, single-cell RNA sequencing or RNA sequencing results.
研究概览
地位
研究类型
注册 (估计的)
阶段
- 第三阶段
联系人和位置
学习联系方式
- 姓名:JunMin Li
- 电话号码:86-21-64374756
- 邮箱:drlijunmin@126.com
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Age between 60 and 80 years old, inclusive.
Diagnosis of acute myeloid leukemia (AML) confirmed by bone marrow morphology and immunophenotyping, meeting all sub-criteria below:
① Bone marrow morphology: Bone marrow blasts <5%, without features of leukemic infiltration;
② Cytogenetics: Carrying common chromosomal abnormalities including t(8;21), t(16;16), t(9;11), t(6;9), t(9;22), etc. Patients with t(15;17)(q22;q21) are excluded;
③ Molecular genetics: Harboring common fusion genes including AML1-ETO, CBFβ-MYH1, MLL-related fusions; patients with positive PML-RARα are excluded. Common gene mutations include NPM1, FLT3-ITD, CEBPA and c-kit;
④ Immunophenotyping: Single-lineage AML with a lymphoid antigen score of 0.
- Achieved complete remission (CR), complete remission with partial hematologic recovery (CRh), or complete remission with incomplete hematologic recovery (CRi) after frontline induction chemotherapy; OR achieved CR/CRh/CRi followed by one cycle of consolidation with the original induction regimen.
- Stratified as intermediate-risk or high-risk AML per the 2022 European LeukemiaNet (ELN) risk classification; patients with TP53 mutation or complex karyotype are excluded.
- Adequate hepatic and renal function: total bilirubin ≤35 μmol/L; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2× upper limit of normal (ULN); serum creatinine ≤150 μmol/L.
- Adequate cardiac function: resting left ventricular ejection fraction (LVEF) ≥50% on echocardiogram.
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2. Written informed consent signed by the patient and/or legal guardian.
Exclusion Criteria:
1.Confirmed diagnosis of acute promyelocytic leukemia (APL). 2.Relapsed or refractory AML, mixed-phenotype acute leukemia, or concomitant other hematological malignancies (including but not limited to lymphoma, multiple myeloma, immune thrombocytopenia (ITP), and other diseases whose treatment with immunosuppressants may interfere with immune reconstitution after cord blood infusion).
3.Known hypersensitivity to any study drug specified in the protocol. 4.Clear contraindication to chemotherapy as judged by the investigator. 5.History of other malignant tumors within the past 5 years, excluding cured basal cell carcinoma of the skin, localized cutaneous squamous cell carcinoma, cervical carcinoma in situ or breast carcinoma in situ.
6.Clinically significant active infection requiring systemic antibiotic therapy (including bacterial, viral and fungal infections) as assessed by the investigator, or seropositive for human immunodeficiency virus (HIV).
7.Active autoimmune diseases requiring systematic treatment within the past 2 years (e.g., diseases requiring corticosteroids or immunosuppressive agents).
8.Pregnant or breastfeeding female patients. 9.Unable to understand or comply with the study protocol. 10.Concurrent participation in another interventional clinical trial. 11.Any other condition that may hinder the implementation of the study, as determined by the investigator.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的:Umbilical Cord Blood Consolidation Therapy
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Subjects in the experimental arm receive consolidation chemotherapy with decitabine plus cytarabine, followed by unrelated cord blood infusion, then maintenance azacitidine after completion of two cord blood infusions. Decitabine is administered at 15 mg/m² per day intravenously on Days 1-5 of each consolidation cycle. Cytarabine 1.0 g/m² is given intravenously every 12 hours on Days 6-7 of each cycle. Unrelated umbilical cord blood (UCB) is infused on Day 9 of each consolidation cycle. UCB eligibility criteria: total nucleated cell (TNC) count >3×10⁷/kg pre-cryopreservation, HLA matching at 4/6 to 5/6 loci, ABO and Rh blood type compatibility preferred. The above consolidation regimen is repeated on Day 30 (counting Day 1 of decitabine as cycle Day 1), or earlier upon hematologic recovery. After completing two UCB infusions, maintenance therapy with azacitidine is initiated the following month: azacitidine 75 mg/m² subcutaneously on Days 1-7 of each 28-day cycle for a total of 12 con |
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有源比较器:Standard Cytarabine Consolidation Therapy
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Standard consolidation chemotherapy with high-dose cytarabine identical azacitidine maintenance therapy as experimental arm, no UCB infusion.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
2-Year Leukemia-Free Survival (LFS)
大体时间:Up to 24 months post randomization
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Time from initiation of study consolidation therapy until hematologic relapse, additional anti-leukemia salvage treatment initiation, or all-cause death within 2 years; proportion of participants without LFS events at 2 years.
MRD defined negative by flow cytometry <0.1%.
|
Up to 24 months post randomization
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
2-Year Overall Survival (OS)
大体时间:Up to 24 months post randomization
|
Proportion of participants alive from treatment initiation to 2 years; all-cause mortality counted as event.
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Up to 24 months post randomization
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MRD Negative Conversion Rate and Sustained MRD-Negative Duration
大体时间:Once monthly during the consolidation and maintenance treatment period, and once every three months during the first year after completion of maintenance treatment.
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Percentage of subjects achieving MRD negative (<0.1%) during follow-up; continuous duration of sustained MRD negativity after first negative test.
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Once monthly during the consolidation and maintenance treatment period, and once every three months during the first year after completion of maintenance treatment.
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Median Time to Neutrophil and Platelet Recovery
大体时间:Baseline (Day 1) and up to 30 days of Consolidation Cycle 1 and Consolidation Cycle 2.
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Neutrophil recovery: first day of 3 consecutive days ANC >0.5×10⁹/L.
Platelet recovery: first day of 3 consecutive days PLT>50×10⁹/L without transfusion support.
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Baseline (Day 1) and up to 30 days of Consolidation Cycle 1 and Consolidation Cycle 2.
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Treatment-Related Mortality (TRM) Rate
大体时间:First 100 days after initial study consolidation
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The proportion of participants who die as a result of treatment-related complications during the study period.
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First 100 days after initial study consolidation
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Incidence of Hematologic & Non-Hematologic Adverse Events
大体时间:up to 2 years
|
Frequency of Grade 1-5 toxicities assessed per CTCAE Version 5.0.
|
up to 2 years
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Chimerism level
大体时间:Assessed on Day 7 after each unrelated umbilical cord blood (UCB) infusion.
|
Assessed on Day 7 after each unrelated umbilical cord blood (UCB) infusion.
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Peripheral blood immune cell transcriptomic profiling by single-cell RNA sequencing
大体时间:Assessed 1 day before and on Day 7 after each UCB infusion.
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Assessed 1 day before and on Day 7 after each UCB infusion.
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Immune re-constitution assessed by flow cytometry-based peripheral blood lymphocyte subset quantification
大体时间:Assessed 1 day before and on Day 7 after each UCB infusion.
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Quantification of peripheral blood lymphocyte subsets (including CD3⁺T-cells, CD4⁺T-cells, CD8⁺T-cells, CD19⁺B-cells, CD16⁺56⁺NK-cells) using multi-parameter flow cytometry.
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Assessed 1 day before and on Day 7 after each UCB infusion.
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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