A Prospective, Single-arm, Multicenter, Open-label , Phase 2 Study to Evaluate Efficacy and Safety of the Daratumumab in T Cell Acute Lymphoblastic Leukemia With Minimal Residual-Positive After Standard Chemotherapy
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 20
- 主要终点
- Rate of conversion from MRD+to MRD- by flow cytometry after 1 cycle of daretuzumab treatment
研究概览
简要总结
T-ALL accounts for about 15%-25% of Ph-negative ALL, and its clinical prognosis is worse than B-ALL. The successful application of immunotherapy has brought revolutionary progress to the treatment of ALL. But progress in the treatment of T-ALL has been relatively slow. Minimal residual disease (MRD) is a strong prognostic indicator for ALL patients. MRD-positive after induction therapy predicts a high risk of relapse. The National Comprehensive Cancer Network (NCCN) considers MRD-positive ALL patients to be at high risk. Research in the B-ALL field has demonstrated that immunotherapy has the potential to further clear MRD, which in turn translates into survival benefits. Daratumumab is a humanized, anti-CD38 IgG1 monoclonal antibody that binds to CD38 expressed by tumor cells. Apoptosis of tumor cells is induced through a variety of immune-related mechanisms such as complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cytophagocytosis (ADCP), and FCγ receptors, which are currently mainly used in the treatment of multiple myeloma. CD38 is highly and stably expressed on the surface of T-ALL cells, and its expression was less influenced by the previous treatment. Preliminary data from the clinical study of daratumumab combined with BFM bone frame prescription for the treatment of recurrent refractory T ALL(NCT03384654) showed that the effectiveness rate (ORR) was 83.3% in children and 60% in young adults. Compared with the previous historical data, the safety and tolerability were significantly improved. For T-ALL patients who relapse after allogeneic transplantation and achieve CR with intense chemotherapy but continue to have MRD-positive flow rate, daratumumab monotherapy can further clear MRD and achieve the purpose of sustaining CR. These studies all demonstrate the potential role of daratumumab in the treatment of T-ALL. Based on the current difficulties in the treatment of T-ALL and existing research data, we plan to conduct a prospective, single-arm, open-label phase II clinical study to explore the efficacy and safety of daratumumab for flow minimal residual disease positive T-ALL after standard chemotherapy.
详细描述
Daratumumab is administered once a week at a dose of 16 mg/kg for a total of 4 times (Day1,8,15,22) in one cycle. Conditions patients can use up to two cycles of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with newly diagnosed T-cell acute lymphoblastic leukemia confirmed by cell morphology and immunophenotype had flow MRD≥0.01% 3 months after chemotherapy; or patients with T-cell acute lymphoblastic leukemia relapsed achieved CR again after salvage chemotherapy, but the flow MRD was ≥0.01%
- •Age ≥18 years old, male or female
- •The expression of CD38 in tumor cells was positive
- •Men and women who may give birth agree to and use effective contraceptive methods
- •Main organ function assessment criteria: total bilirubin < 1.5× upper normal limit (ULN), glutamic oxalic aminotransferase (AST) and glutamic alanine aminotransferase (ALT) ≤2.5×ULN; Serum creatinine < 2×ULN; Myocardial enzyme < 2×ULN; Serum amylase ≤1.5×ULN; Left ventricular ejection fraction (LEF) was > 45%
- •Understand and sign the informed consent and agree to comply with the study requirements
排除标准
- •SAEs related to the study emerged during the study, and the investigator judged that the necessity of quitting the project was greater than the benefit
- •In case of any situation in which the subjects could not tolerate the study regimen, the investigator assessed that the necessity of withdrawal from the regimen outweighed the benefit
- •The subject had an allergic reaction to any drug of the study regimen or other conditions that prevented the regimen from continuing
- •Subjects voluntarily asked to withdraw from the study at any time
- •Any situation in which the investigator determines that the benefit of withdrawing from the study outweighs the benefit
研究组 & 干预措施
Daratumumab
Daratumumab was administered once a week at a dose of 16 mg/kg for a total of 4 times (Day1,8,15,22 dosing patterns) in one cycle. Patients with conditions may use up to two cycles of treatment.
干预措施: Daratumumab Injection (Drug)
结局指标
主要结局
Rate of conversion from MRD+to MRD- by flow cytometry after 1 cycle of daretuzumab treatment
时间窗: up to 28days ±3days after daretuzumab treatment
If no abnormal phenotypic leukemia cells were detected by flow cytometry, flow MRD-negative was considered
次要结局
- Rate of conversion from MRD+to MRD- by NGS(up to 2 years after the date of the last enrolled participants)
- 30-day mortality(Within 30 days of the date of the last enrolled participants)
- 60-day mortality(Within 60 days of the date of the last enrolled participants)
- overall survival overall survival overall survival(up to 2 years after the date of the last enrolled participants)
- Disease-free survival (DFS)(up to 2 years after the date of the last enrolled participants)
- Cumulative incidence of relapse (CIR)(up to 2 years after the date of the last enrolled participants)
- duration of MRD-negative response(up to 2 years after the date of the last enrolled participants)