NCT04796688

Universal Chimeric Antigen Receptor-modified AT19 Cells for CD19+ Relapsed/Refractory Hematological Malignancies

Safety and Efficacy of Universal Chimeric Antigen Receptor-modified AT19 Cells in Patients With CD19+ Relapsed/Refractory Hematological Malignancies: a Single-center, Open-label, Single-arm Clinical Study

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (estimated)
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology · Academic / Other
• Sex: All
• Age: 14 Years – 78 Years
• Healthy volunteers: Not accepted

Summary

This is a single-center, open-label, single-arm study to evaluate the primary safety and efficacy of universal chimeric antigen receptor-modified AT19 cells in patients with relapsed or refractory hematological malignancies.

Detailed description

* Adoptive transfer of autologous anti-CD19 CAR-T cells can induce durable remissions in patients with relapsed/refractory hematologic malignancies, including CD19+ B-cell acute lymphoblastic leukemia(B-ALL), B-cell chronic lymphoblastic leukemia(B-CLL), and B-cell lymphoma. * However, multiple challenges exist for manufacturing CAR-T cells from patients with advanced disease including inability to manufacture a product, disease progression or death while waiting for the CAR-T product to be available, and heterogeneity among autologous CAR-T products that contributes to unpredictable and variable clinical activity. * Healthy donor T cells can provide a source for production of universal CAR-T cells when combined with gene editing to prevent expression of endogenous TCRs and avoid generation of GvHD in HLA mismatched recipients. * Cord blood derived T cells from healthy donor are the source for production of universal anti-CD19 CAR-modified AT19 cells. CRISPR/cas9 gene-editing technology has been used to knockout TCRs and HLA-I to avoid GvHD and transplant rejection. * AT19 cells have exhibited potent cytotoxicity in CD19+ tumor cells and can effectively eradicate CD19+ tumor cells in xenograft mice models, without showing GvHD. * This study aims to evaluate prelimary safety and efficacy of the universal AT19 cells in patients with relapsed/refractory B-ALL, B-CLL, and B-cell lymphoma.

Conditions

• Acute Lymphoblastic Leukemia
• Chronic Lymphoblastic Leukemia
• B-cell Lymphoma

Interventions

Type	Name	Description
DRUG	Fludarabine + Cyclophosphamide + CAR-NK-CD19 Cells	fludarabine 30 mg/kg on day -5, -4, and -3; cyclophosphamide 300 mg/kg on day -5, -4, and -3; CAR-NK-CD19 Cells on day 0.

Timeline

• Start date: 2021-03-10
• Primary completion: 2023-03-10
• Completion: 2024-03-10
• First posted: 2021-03-15
• Last updated: 2021-03-15

Locations

2 sites across 1 country: China