Adding CLS-015 to anti-CD19 CAR-T therapy for large B‑cell lymphoma during lymphodepletion
Official title: 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.
Run by Tel-Aviv Sourasky Medical Center · NCT07361224 · Data updated 2026-11-12
This trial tests whether giving CLS-015 (an enzyme that breaks down NETs) alongside anti‑CD19 CAR‑T therapy helps adults with large B‑cell lymphoma who have stable or progressing disease at the time of lymphodepletion.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years and up |
| Sex | All |
| Enrollment | 12 (estimated) |
| Sponsor | Tel-Aviv Sourasky Medical Center Government |
| Drugs / interventions | CAR-T, CAR T |
| Locations | 1 site (Tel Aviv) |
| Status | Recruiting |
| Started | May 2026 |
| Main results expected | February 2027 |
| Study ends | February 2028 |
| Registry record updated | May 1, 2026 |
| Trial ID | NCT07361224 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a good fit
Adults (≥18) with large B‑cell lymphoma who are receiving CD19‑targeted CAR‑T therapy and have stable disease or progressive disease confirmed by PET‑CT at the time of lymphodepletion, with ECOG 0–2 and ability to consent, are the intended participants.
✕Probably not a fit
Patients who are in partial or complete response at lymphodepletion, who are pregnant or breastfeeding, who have active infection requiring antibiotics, or who have hypersensitivity to CLS‑015 are unlikely to benefit from this protocol.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
What this trial studies
This is a Phase 1, single‑center, open‑label trial that gives CLS‑015 (rhDNase I) intravenously on days 0, 3, 6, 10, and 15 after CAR‑T infusion to patients with large B‑cell lymphoma who show stable disease or progressive disease during lymphodepletion. The rationale is that neutrophil extracellular traps (NETs) can impair CAR‑T cell function and tumor penetration, and enzymatically degrading NETs may improve CAR‑T activity and reduce early progression. Participants will be monitored with blood tests, CAR‑T cell levels, and tracking of cytokine release syndrome and other adverse events. The study focuses on safety in this high‑risk population and will collect preliminary signals of clinical benefit.
Why it matters
Potential benefit: If successful, adding CLS‑015 could increase CAR‑T effectiveness and reduce the high risk of early disease progression in patients with SD or PD during lymphodepletion.
How similar studies have gone: Preclinical studies indicate CLS‑015 can enhance CAR‑T activity and reduce NETs, but clinical data combining DNase with CAR‑T therapy are novel and currently unproven.
Who can join: the full rules
Show full inclusion / exclusion criteria
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
Where it's running
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Sourasky Medical Center
Tel Aviv, Israel Recruiting
Study contacts
- Principal investigator: Ron Ram, Prof. — Sourasky Medical Center
- Study coordinator: Ron Ram, Prof.
- Email: ronr@tlvmc.gov.il
- Phone: 972-3-6973782
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.