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.

April 27, 2026 updated by: Tel-Aviv Sourasky Medical Center

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Israel
      • Tel Aviv, Israel, 6423906
        • Recruiting
        • Sourasky Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participant must be at least 18 years of age inclusive, at the time of signing the informed consent.
  • Large B-Cell lymphoma treated with CAR-T targeting CD19 (tisagenlecleucel, axicabtagene ciloleucel, or lisocabtagene maraleucel)
  • Stable Disease or Progressive Disease confirmed by PET-CT on the day of lymphodepletion
  • Capable of giving signed informed consent
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion Criteria:

  • Hypersensitivity to CLS-015
  • Evidence of any clinically significant condition, disorder, condition, or disease that, in the opinion of the Investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
  • Active infection requiring antibiotics
  • Females only: Pregnant or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: CLS-015 infusions after CAR-T infusion
CLS-015 infusions will be done on Days 0,3,6,10 and 15 after CAR-T infusion
Drug: rhDNase I
CLS-015 IV infusions after CAR-T infusion done on Days 0,3,6,10 and 15 after CAR-T infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate the safety and tolerability of CLS-015 in combination with anti CD19 CAR T therapy in subjects with stable/progressive Large B-Cell lymphoma at lymphodepletion when CLS-015 is given in adjuvant setting.
Time Frame: Through study completion, an average of 2 years.
Safety and tolerability of CLS-015 based on adverse events evaluation and recording will be evaluated from screening to the end of study.
Through study completion, an average of 2 years.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tel-Aviv Sourasky Medical Center

Investigators

  • Principal Investigator: Ron Ram, Prof., Sourasky Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2026

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

February 1, 2028

Study Registration Dates

First Submitted

January 4, 2026

First Submitted That Met QC Criteria

January 14, 2026

First Posted (Actual)

January 22, 2026

Study Record Updates

Last Update Posted (Actual)

May 1, 2026

Last Update Submitted That Met QC Criteria

April 27, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0126-25

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

The plan for sharing individual participant data has not yet been determined at this time

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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