CD19 CAR-T vs DLI for Post-HSCT MRD in Ph- ALL: A RCT

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.

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