A Prospective, Multicenter, Randomized-Controlled Study of Cord Blood Consolidation Therapy for Intermediate- and High-Risk Elderly Acute Myeloid Leukemia
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 132
- 主要终点
- 2-Year Leukemia-Free Survival (LFS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 60 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
- •Written informed consent signed by the patient and/or legal guardian.
排除标准
- •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.
研究组 & 干预措施
Umbilical Cord Blood Consolidation Therapy
干预措施: Unrelated Umbilical Cord Blood Infusion (Biological)
Standard Cytarabine Consolidation Therapy
干预措施: Standard consolidation chemotherapy with high-dose cytarabine (Drug)
结局指标
主要结局
2-Year Leukemia-Free Survival (LFS)
时间窗: Up to 24 months post randomization
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%.
次要结局
- 2-Year Overall Survival (OS)(Up to 24 months post randomization)
- MRD Negative Conversion Rate and Sustained MRD-Negative Duration(Once monthly during the consolidation and maintenance treatment period, and once every three months during the first year after completion of maintenance treatment.)
- Median Time to Neutrophil and Platelet Recovery(Baseline (Day 1) and up to 30 days of Consolidation Cycle 1 and Consolidation Cycle 2.)
- Treatment-Related Mortality (TRM) Rate(First 100 days after initial study consolidation)
- Incidence of Hematologic & Non-Hematologic Adverse Events(up to 2 years)
研究者
Junmin Li
Chief Physician of hematology
Shanghai Jiao Tong University School of Medicine