Effectiveness and Safety of Blinatumomab and Donor Lymphocyte Infusion in Maintenance Therapy After Allogeneic Hematopoietic Stem Cell Transplantation for High-risk Ph Negative B Cell Acute Lymphoblastic Leukemia：Phrase II, Exploratory Study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- The 2-year leukemia-free survival (LFS) after allo-HSCT.
研究概览
简要总结
A single-arm trial to evaluate the effectiveness and safety of Blinatumomab and Donor Lymphocyte Infusion in maintenance therapy after allogeneic hematopoietic stem cell transplantation for high-risk Ph negative B cell acute lymphoblastic leukemia
详细描述
Currently, the treatment for Philadelphia chromosome (Ph)-negative adult B-cell acute lymphoblastic leukemia (B-ALL) primarily relies on traditional multi-agent combination chemotherapy. Clinical efficacy is closely associated with patient age, genetic characteristics, chemotherapy sensitivity, and minimal residual disease (MRD) status post-remission. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most critical curative approach for Ph-negative B-ALL. However, high-risk patients, such as those with refractory/relapsed B-ALL or MRD positivity before transplantation, exhibit significantly higher post-transplant relapse rates, reported at approximately 48%-59%, with a disease-free survival rate of less than 40%.
Multiple studies have reported that blinatumomab achieves complete remission rates of 33-50% in refractory/relapsed Ph-negative B-ALL. Previous research has shown that post-transplant blinatumomab is well-tolerated, with no treatment-related mortality, and the most common severe adverse event being cytopenia. The efficacy of blinatumomab as post-transplant prophylactic therapy depends on T-cell function.
Donor lymphocyte infusion (DLI) is widely used for the prevention and treatment of relapse after allo-HSCT. The investigators prior matched case-control study demonstrated that prophylactic DLI could reduce relapse and improve survival in high-risk acute leukemia patients after haploidentical peripheral blood stem cell transplantation. DLI products are rich in T lymphocytes, which can reverse T-cell exhaustion by altering the composition of cellular subsets in the patient's body, thereby exerting an anti-leukemic effect.
Based on the above rationale, the investigators are conducting this clinical study: a single-arm, phase II, multicenter trial to evaluate the efficacy and safety of blinatumomab combined with donor lymphocyte infusion as maintenance therapy in high-risk Ph-negative B-ALL patients after allo-HSCT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 14-65 years (inclusive), regardless of gender.
- •Newly diagnosed B-ALL with CD19 expression on leukemic cells (regardless of CD19 positivity rate).
- •Ph-negative B-ALL with high-risk features post-allo-HSCT .
- •≥2 months post-transplant with hematopoietic reconstitution.
- •Bone marrow morphology in remission and MRD-negative before enrollment.
- •ECOG performance status <3 and Karnofsky score ≥
- •No history of grade III/IV graft-versus-host disease (GVHD) and no active GVHD at enrollment.
- •Adequate organ function:AST and ALT ≤3× upper limit of normal (ULN), total bilirubin ≤2×ULN.Serum creatinine ≤2×ULN or creatinine clearance ≥50 mL/min (calculated by Cockcroft-Gault formula).Left ventricular ejection fraction (LVEF) ≥50% by echocardiography (ECHO).
- •Expected survival >3 months.
- •Voluntary provision of written informed consent, with ability to understand and comply with study requirements.
排除标准
- •History of hypersensitivity or severe adverse reactions to the study drug or structurally similar compounds, as assessed by the investigator to preclude participation.
- •Pregnant or lactating women, or women of childbearing potential unwilling to use effective contraception.
- •Severe cardiac dysfunction, including:Left ventricular ejection fraction (EF) <60%.Clinically significant arrhythmias (e.g., ventricular tachycardia, atrial fibrillation, second-degree heart block).Prolonged QTc interval (men >450 ms; women >470 ms).Myocardial infarction within the past year.Symptomatic coronary artery disease requiring medication.
- •Severe pulmonary dysfunction (obstructive and/or restrictive ventilatory impairment).
- •Severe hepatic impairment:ALT or total bilirubin (TBIL) >3× upper limit of normal (ULN).
- •Severe renal impairment:Serum creatinine (Cr) >2× ULN.24-hour creatinine clearance (Ccr) <50 mL/min.
- •Active infection or uncontrolled bleeding, as assessed by the investigator to preclude safe administration of the study drug.
- •History of thrombosis, embolism, cerebral hemorrhage, or other significant vascular events within the past year.
- •Psychiatric disorders or other conditions that impair the ability to provide informed consent or comply with study procedures.
- •Major organ surgery within the past six weeks.
- •Drug abuse or chronic alcoholism that may interfere with study assessments.
- •Prior organ transplantation (excluding hematopoietic stem cell transplantation).
- •Other conditions deemed by the investigator to make the patient unsuitable for participation.
研究组 & 干预措施
Blinatumomab and Donor Lymphocyte Infusion
干预措施: BITE and DLI (Drug)
结局指标
主要结局
The 2-year leukemia-free survival (LFS) after allo-HSCT.
时间窗: 2 years
次要结局
- The 2-year overall survival（OS）(2 years)
- The 2-year cumulative incidence of relapse(2-years)
- The 2-year cumulative incidence of non-relapse mortality(NRM)(2-years)