Overview
This prospective, open-label randomized controlled trial compares CD19 CAR-T therapy with chemotherapy plus donor lymphocyte infusion (DLI) in 70 patients with Ph-negative B-cell acute lymphoblastic leukemia (B-ALL) who exhibited minimal residual disease (MRD) positivity (≥0.1% CD19+ abnormal B cells) after allogeneic hematopoietic stem cell transplantation (HSCT).
Patients (aged 3-\<80 years, ECOG 0-2, no relapse, adequate organ function) were randomized to receive either autologous CD19 CAR-T cells following lymphodepletion or conventional chemotherapy with DLI.
The primary endpoint is the MRD negativity rate at 3 months. Secondary endpoints include 1-year MRD positivity, relapse rate, overall survival, disease-free survival, GVHD incidence, GVHD-free relapse-free survival, and duration of severe hematological toxicity.
The study includes a 1-year follow-up and permits crossover to the alternative treatment for patients with persistent MRD (≥0.1%) at 3 months in the absence of relapse.
Description
Objective: This prospective, open-label, randomized controlled trial (RCT) aims to compare the efficacy and safety of CD19 chimeric antigen receptor T-cell (CAR-T) therapy versus chemotherapy plus donor lymphocyte infusion (DLI) in patients with Ph-negative acute B-lymphoblastic leukemia (Ph- B-ALL) positive for minimal residual disease (MRD) after allogeneic hematopoietic stem cell transplantation (HSCT).
Study Population: A total of 70 eligible patients will be randomized 1:1 to the experimental group (CD19 CAR-T, n=35) or control group (chemotherapy + DLI, n=35).
- Interventions
Experimental group: Autologous CD19 CAR-T cells (1.0×10⁶/kg, single intravenous infusion) following lymphodepletion with cyclophosphamide (300mg/m²/d ×3d) + fludarabine (30mg/m²/d ×3d); no bridging chemotherapy allowed.
Control group: Chemotherapy combined with DLI.
Study Endpoints:
Primary endpoint: MRD negativity rate at 3 months post-treatment. Secondary endpoints: 1-year MRD positivity rate, hematological/extramedullary relapse rate, overall survival (OS), disease-free survival (DFS), incidence of grade II-IV acute GVHD (aGVHD), NIH moderate-to-severe chronic GVHD (cGVHD), graft-versus-host disease-free relapse-free survival (GRFS), and duration of grade III-IV hematological toxicity.
Study Duration: Enrollment starts with the first patient's treatment; study conclusion is 1 year after the last patient's treatment. Efficacy assessments are conducted at 1, 2, 3, 4, 5, 6, 9, and 12 months post-treatment.
Crossover Design: Patients with persistent MRD (≥0.1%) at 3 months without relapse may crossover: experimental group to chemotherapy + DLI, control group to CD19 CAR-T therapy (with informed consent).
Statistical Analysis: Sample size is calculated based on a superior design (90% vs 60% 3-month MRD negativity rate in CAR-T vs control group; α=0.05, β=0.2, 10% dropout rate). Categorical variables are summarized as counts/proportions (95% CI); continuous variables as mean/median (SD/range). Survival data (OS, DFS) will be analyzed using Kaplan-Meier methods and log-rank tests.
Eligibility
Inclusion Criteria:
- age 3-\<80 years
- ECOG performance status 0-2
- post-HSCT MRD positivity (≥0.1% CD19+ abnormal B cells by flow cytometry)
- no hematological/extramedullary relapse
- adequate organ function
- negative pregnancy test (for fertile females)
Exclusion Criteria:
- active infections
- uncontrolled graft-versus-host disease (GVHD)
- history of central nervous system disorders
- autoimmune diseases
- other active malignancies
