Full-course Immunotherapy Combined With Chemotherapy in Newly Diagnosed B-cell Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 101
- 试验地点
- 1
- 主要终点
- 2-year relapse-free survival (RFS)
研究概览
简要总结
This is a single-arm, prospective, phase 2 clinical trial evaluating the improvement of survival outcomes of blinatumomab combined with chemotherapy as a full-course treatment regimen in patients with newly diagnosed Philadelphia chromosome-negative (Ph-negative) B-cell precursor acute lymphoblastic leukemia (B-ALL). The study adopts a "reduced-dose chemotherapy + full-course immunotherapy" strategy: induction therapy with reduced-dose chemotherapy combined with blinatumomab to improve remission rate and tolerability; consolidation therapy with alternating Hyper-CVAD (A/B) regimen，blinatumomab and sequential CD19-directed CAR-T therapy to deepen minimal residual disease (MRD) clearance; allogeneic hematopoietic stem cell transplantation (allo-HSCT) for some patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence); and no maintenance therapy.
The primary endpoint is 2-year relapse-free survival (RFS). Secondary endpoints include 2-year overall survival (OS), the proportion and time to achieve complete response (CRc), and the proportion and time to achieve minimal residual disease (MRD) negativity.
The trial plans to enroll 101 patients aged 15-65 years to demonstrate improved survival outcomes compared with historical controls .
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
- 15 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥15 years and ≤65 years.
- •Newly diagnosed Ph-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) according to WHO diagnostic criteria, with CD19 expression ≥ 20%
- •De novo patients with no prior induction therapy (excluding hydroxyurea and corticosteroid use for ≤ 5 days)
- •ECOG performance status score 0-
- •Liver function: Total bilirubin ≤ 3 times the upper limit of normal (ULN); alanine transaminase (ALT) ≤ 3×ULN; aspartate transaminase (AST) ≤ 3×ULN; (leukemic infiltration is excluded).
- •Renal function: Creatinine clearance rate (CrCl) ≥ 30 mL/min
- •Able to understand and voluntarily participate in the study, and provide written informed consent
排除标准
- •Philadelphia chromosome-positive (Ph+, BCR-ABL1+) ALL
- •T-cell acute lymphoblastic leukemia
- •Mature B-cell leukemia/lymphoma, B-cell lymphoblastic lymphoma, extramedullary invasion
- •Acute mixed phenotype acute leukemia (MPAL)
- •Central nervous system (CNS) leukemia
- •HIV infection
- •Positive HBV-DNA or HCV-RNA
- •New York Heart Association (NYHA) functional class ≥ II, or other conditions deemed unsuitable for enrollment by the investigator
- •Pregnant or lactating patients
- •Patients who refuse to enroll in the study
研究组 & 干预措施
Experimental Arm:Blinatumomab + Chemotherapy
Patients receive reduced-dose chemotherapy combined with blinatumomab for induction, followed by alternating Hyper-CVAD(A/B) chemotherapy, blinatumomab and sequential CD19-directed CAR-T therapy for consolidation. Patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence)receive allogeneic hematopoietic stem cell transplantation.
干预措施: Blinatumomab (Biological)
Experimental Arm:Blinatumomab + Chemotherapy
Patients receive reduced-dose chemotherapy combined with blinatumomab for induction, followed by alternating Hyper-CVAD(A/B) chemotherapy, blinatumomab and sequential CD19-directed CAR-T therapy for consolidation. Patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence)receive allogeneic hematopoietic stem cell transplantation.
干预措施: Induction Chemotherapy (Drug)
Experimental Arm:Blinatumomab + Chemotherapy
Patients receive reduced-dose chemotherapy combined with blinatumomab for induction, followed by alternating Hyper-CVAD(A/B) chemotherapy, blinatumomab and sequential CD19-directed CAR-T therapy for consolidation. Patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence)receive allogeneic hematopoietic stem cell transplantation.
干预措施: Hyper-CVAD (Drug)
Experimental Arm:Blinatumomab + Chemotherapy
Patients receive reduced-dose chemotherapy combined with blinatumomab for induction, followed by alternating Hyper-CVAD(A/B) chemotherapy, blinatumomab and sequential CD19-directed CAR-T therapy for consolidation. Patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence)receive allogeneic hematopoietic stem cell transplantation.
干预措施: Allogeneic hematopoietic stem cell transplantation (Procedure)
Experimental Arm:Blinatumomab + Chemotherapy
Patients receive reduced-dose chemotherapy combined with blinatumomab for induction, followed by alternating Hyper-CVAD(A/B) chemotherapy, blinatumomab and sequential CD19-directed CAR-T therapy for consolidation. Patients (e.g., KMT2A rearrangement, TP53 mutation, persistent MRD positivity, MRD recurrence)receive allogeneic hematopoietic stem cell transplantation.
干预措施: CAR-T cell therapy (Biological)
结局指标
主要结局
2-year relapse-free survival (RFS)
时间窗: From enrollment through 2 years post-last patient enrolled
Defined as the time from enrollment to relapse, death from any cause, or last follow-up, whichever occurs first.
次要结局
- 2-year overall survival (OS)(From enrollment through 2 years post-last patient enrolled)
- Composite Complete Remission (CR/CRi) Rate after Induction Therapy(From randomization to 2 cycles of induction before consolidation therapy(100 days))
- Minimal Residual Disease (MRD) Negativity Rate(From randomization to 2 cycles of induction before consolidation therapy(100 days))
研究者
Chen Suning
Doctor
The First Affiliated Hospital of Soochow University