A Single-arm, Open-label, Phase I Clinical Study of Blinatumomab Combined With Low-dose DLI as Maintenance Therapy After Transplantation for B-ALL
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- 1 year progression-free-survival
研究概览
简要总结
This prospective study will be conducted in high-risk B-ALL patients post-allo-HSCT. We propose to investigate the safety and therapeutic efficacy of blinatumomab plus low-dose DLI maintenance therapy, with the ultimate goal of enhancing long-term survival outcomes.
详细描述
This study is a single-center, prospective, single-arm Phase I clinical trial. Since July 2023, 12 patients with high-risk acute B-lymphoblastic leukemia who underwent allogeneic hematopoietic stem cell transplantation were enrolled at the Department of Hematology, the PLA General Hospital . Patients were enrolled after 45d for MSD-HSCT, and after 60d for URD/Haplo donor-HSCT. The maintenance regimen combined blinatumomab (9 µg/day × 7 days) and donor lymphocyte infusion (DLI, CD3+ cells 1× 10⁵/kg). The first cycle was given within the first 3 months after allogeneic HCT and then at approximately 6, 9, and 12 months following transplant. The safety and efficacy of this regimen were analyzed. Patients were premedicated with dexamethasone prior to the start of each cycle. The study was approved by the Ethics Committee of the PLA General Hospital.
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
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1) Voluntary participation: The participant or legal guardian fully understands this clinical study, provides informed consent (ICF), and is willing/able to comply with all trial procedures.
- •2) Age: <70 years old at screening, any gender. 3) Diagnosis: High-risk acute B-lymphoblastic leukemia (B-ALL) with MRD-negative status post-transplant. High-risk factors include:
- •>CR1 status
- •Pre-transplant MRD+ status
- •Ph-like subtype
- •KMT2A rearrangement
- •Other high-risk cytogenetic/genetic factors per ELN 2023 criteria. 4) Allergy: No history of severe allergies. 5) Liver function: ALT and AST ≤ 2.5 × ULN; Total bilirubin ≤ 2 × ULN. 6) Renal function: Serum creatinine ≤ ULN. 7) Other conditions: Absence of uncontrolled infections or severe psychiatric disorders.
- •8) Performance status: ECOG score 0-3, with life expectancy ≥ 4 months. 9) MRD status: Bone marrow flow cytometry confirmed MRD-negative before enrollment.
- •10) Engraftment: Evidence of myeloid and platelet engraftment. 11) GVHD: No active graft-versus-host disease (GVHD).
排除标准
- •1) Drug hypersensitivity/contraindications: Patients with known allergies or contraindications to the investigational drug(s).
- •2) Pregnancy/lactation: Pregnant or breastfeeding female patients. 3) Active infection/GVHD: Patients with active infection or active graft-versus-host disease (GVHD).
- •4) Substance abuse: Patients with chronic heavy smoking or alcohol use that may interfere with clinical evaluation.
- •5) Impaired consent/compliance: Patients unable to provide informed consent or comply with procedures due to psychiatric/neurological disorders.
- •6) Recent major surgery: Patients who underwent major organ surgery within the past 6 weeks.
- •7) Organ dysfunction:
- •Liver: ALT or AST > 2.5 × ULN; Total bilirubin > 2 × ULN
- •Kidney: Serum creatinine > ULN 8) Investigator judgment: Patients deemed ineligible by investigators (e.g., poor compliance, substance abuse).
结局指标
主要结局
1 year progression-free-survival
时间窗: 1 year
the percentage of patients who remain alive and whose disease has not gotten relapse one full year after they started treatment.
次要结局
- 1 year aGVHD rate(100 days after transplantation)
- 1 year cGVHD rate(365 days after transplantation)
- Nonrelapse mortality (NRM)(365 days after transplantation)
- Overall survival (OS)(365 days after transplantation)
研究者
Liping Dou
director
Chinese PLA General Hospital