NCT06880913

Nanobody-Based CD19/CD22 Tandem Dual CAR-T Therapy for R/R B-ALL

A Phase I Dose-Escalation and Phase II Study of Nanobody-Based CD19/CD22 Tandem Dual Chimeric Antigen Receptor (CAR) T-cell Therapy in Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Peking University People's Hospital · Academic / Other
• Sex: All
• Age: 12 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

To evaluate the efficacy and safety of Nanobody-Based CD19/CD22 Tandem Dual Chimeric Antigen Receptor (CAR) T-cell therapy in patients with relapsed or refractory B-ALL

Detailed description

This Phase I/II study aims to evaluate the safety, tolerability, and efficacy of Nanobody-Based CD19/CD22 Tandem Dual CAR-T-cell therapy in patients with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), particularly those who have failed or relapsed after CD19- or CD22-targeted CAR-T or antibody-based immunotherapy. In the Phase I portion of the study, a 3+3 dose-escalation design will be employed to evaluate safety and determine the optimal dose of Nanobody-Based CD19-22 Tandem CAR-T cells. Three dose levels will be tested: 0.3 × 10⁶ cells/kg, 1.0 × 10⁶ cells/kg, and 2.0 × 10⁶ cells/kg. The recommended Phase II dose (RP2D) will be established based on safety data, dose-limiting toxicities (DLTs), and preliminary efficacy outcomes. The Phase II portion will focus on evaluating the efficacy of nanobody-based CD19/CD22 tandem dual CAR-T therapy at the RP2D in patients with R/R B-ALL who are refractory to or have relapsed after prior immunotherapies, including blinatumomab, inotuzumab ozogamicin, or prior single-target CAR-T therapy, with key endpoints including overall response rate (ORR), duration of response (DOR), disease-free survival (DFS), and overall survival (OS).Safety assessments will include cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), immune effector cell-associated hemophagocytic syndrome (IEC-HS), and immune effector cell-associated hematotoxicity (ICAHT) will also be conducted throughout the study. This study seeks to address the unmet clinical need for effective treatment options in patients with R/R B-ALL, particularly those who have exhausted prior CD19- or CD22-directed therapies.

Conditions

• Precursor B-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Type	Name	Description
BIOLOGICAL	Nanobody-Based CD19/CD22 Tandem Dual CAR-T	Phase I: Patients will receive a single infusion of autologous CD19/CD22 dual CAR-T cells at one of three dose levels (0.3 × 10⁶ cells/kg, 1.0 × 10⁶ cells/kg, or 2.0 × 10⁶ cells/kg) following fludarabine (25-30mg/m2\*3d) and cyclophosphamide (250-300mg/m2\*3d) (FC) lymphodepleting chemotherapy. Phase II: Patients will receive autologous CD19/CD22 dual CAR-T cells at the RP2D following FC lymphodepleting chemotherapy.

Timeline

• Start date: 2024-11-14
• Primary completion: 2026-12-31
• Completion: 2028-12-31
• First posted: 2025-03-18
• Last updated: 2026-03-30

Locations

1 site across 1 country: China