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

CD19 Chimeric Antigen Receptor T-Cell Therapy Versus Donor Lymphocyte Infusion for Minimal Residual Disease in Patients With Ph-Negative Acute B-Lymphoblastic Leukemia After Hematopoietic Stem Cell Transplantation: A Prospective, Open-Label, Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: MRD-positive; B ALL; Allogenetic Hematopoietic Stem Cell Transplantation
• Intervention / Treatment: Biological: CAR-T; Biological: DLI

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jing Liu, Doctor; Phone Number: 8610-88326900; Email: greenimp@163.com

Study Locations

• China
  • China
    • Beijing, China, China, 100044
      • Recruiting
      • Peking University People's Hospital
      • Contact: Jing Liu; Phone Number: 8610-88326900; Email: greenimp@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-T group; Autologous CD19 CAR-T (1.0×10⁶/kg, single IV infusion) after cyclophosphamide + fludarabine lymphodepletion (no bridging chemo).	Biological: CAR-T; 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.
Active Comparator: Control group; Chemotherapy + DLI	Biological: DLI; Chemotherapy combined with DLI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-month MRD negativity rate	MRD negativity rate of MFC	3-month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1-year MRD negativity rate	1-year MRD negativity rate of MFC	1-year
relapse rate	relapse rate of leukemia	1-year
OS	overall survival	1-year
DFS	Disease free survival	1-year
GVHD incidence	the rate and degree of aute and chronic graft versus host disease	1-year
GRFS	GVHD and relapse free survival	1-year
grade III-IV hematological toxicity duration	grade III-IV hematological toxicity duration	3 months

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): December 30, 2028

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: February 24, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): February 27, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Minimal Residual Disease (MRD); CD19 CAR-T; Hematopoietic Stem Cell Transplantation (HSCT); Ph-negative B-ALL; Donor Lymphocyte Infusion (DLI)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Pathological Conditions, Signs and Symptoms; Neoplasm, Residual
• Other Study ID Numbers: CD19 CAR-T vs DLI for MRD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No