NCT07361224

Investigator Initiated Study to Assess the Safety of Combination of CLS-015 With Anti-CD-19 CAR-T Cells in Patients With Stable/Progressive Large B Cell Lymphoma at Lymphodepletion.

CLS-015-TAMSC-LBCL-PR An Exploratory, Investigator Initiated Study to Assess the Safety of Combination of CLS-015 (DFF) With Anti-CD-19 CAR-T Cells in Patients With Stable/ Progressive Large B Cell Lymphoma at Lymphodepletion.

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Tel-Aviv Sourasky Medical Center · Other Government
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase 1, single-center, open-label study to evaluate the safety of CLS-015 in combination with anti-CD19 CAR-T therapy in patients with large B-cell lymphoma. The goal is to improve clinical response by reversing the negative effects of NETs on immune function and CAR-T cells.

Detailed description

Disease progression in large B-cell lymphoma is a major obstacle to successful CAR-T therapy, with approximately 40% of patients experiencing disease progression within 3 months of CAR-T infusion and 60% of patients experiencing disease progression within the first year. While patients with large B-cell lymphoma in partial response or complete response during lymphodepletion have a progression-free survival (PFS) of 60-80% at 1 year, patients with stable disease (SD) or progressive disease (PD) in the lymphodepletion phase have a poor PFS of 20-30%. Patients with SD/PD in the lymphoid depletion phase, particularly those with low CAR-T concentrations on day +7, are at very high risk of early disease progression after CAR-T infusion, and there is an urgent and unmet medical need to improve their outcomes. Preclinical studies have shown that CLS-015 enhances the performance of CAR T-cell therapy against CD19-expressing malignancies through various mechanisms, including enhancing CAR T-cell activity, preventing T-cell exhaustion, reducing cytokine release syndrome (CRS), and enhancing CAR-T cell penetration into areas with lymphoma cells by enzymatically degrading NETs in tumor tissue and the bloodstream. All patients enrolled in the study with large B-cell lymphoma in SD/PD during lymphodepletion will receive CLS-015 on days 0, 3, 6, 10, and 15 after CAR-T cell infusion, as an intravenous infusion. Patient will be followed for blood test, incidence and severity of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), immune effector cell-associated HLH-like syndrome (IEC-HS), and cytopenias. Follow up in the study will be done daily for 15 days post CAR-T infusion, then twice weekly for 15 more days. More checkups will be done at 2-, 6-, 9- and 12-months post CAR-T infusion.

Conditions

• Large B-Cell Lymphoma (LBCL)

Interventions

Type	Name	Description
DRUG	rhDNase I	CLS-015 IV infusions after CAR-T infusion done on Days 0,3,6,10 and 15 after CAR-T infusion

Timeline

• Start date: 2026-02-01
• Primary completion: 2027-02-01
• Completion: 2028-02-01
• First posted: 2026-01-22
• Last updated: 2026-01-22