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.

NCT07361224 | Recruiting Phase 1 DMC

• 1 other identifier: 0126-25
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Large B-Cell Lymphoma (LBCL)

Keywords

Large B-Cell lymphoma

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

Study Arms (1)

CLS-015 infusions after CAR-T infusion

EXPERIMENTAL

CLS-015 infusions will be done on Days 0,3,6,10 and 15 after CAR-T infusion

Drug: rhDNase I

Interventions

rhDNase I DRUG

CLS-015 IV infusions after CAR-T infusion done on Days 0,3,6,10 and 15 after CAR-T infusion

CLS-015 infusions after CAR-T infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead

Study Sites (1)

Sourasky Medical Center

Tel Aviv, 6423906, Israel

RECRUITING

Related Publications (4)

• Nie M, Yang L, Bi X, Wang Y, Sun P, Yang H, Liu P, Li Z, Xia Y, Jiang W. Neutrophil Extracellular Traps Induced by IL8 Promote Diffuse Large B-cell Lymphoma Progression via the TLR9 Signaling. Clin Cancer Res. 2019 Mar 15;25(6):1867-1879. doi: 10.1158/1078-0432.CCR-18-1226. Epub 2018 Nov 16.

  PMID: 30446590 BACKGROUND

• Borghaei H, Gettinger S, Vokes EE, Chow LQM, Burgio MA, de Castro Carpeno J, Pluzanski A, Arrieta O, Frontera OA, Chiari R, Butts C, Wojcik-Tomaszewska J, Coudert B, Garassino MC, Ready N, Felip E, Garcia MA, Waterhouse D, Domine M, Barlesi F, Antonia S, Wohlleber M, Gerber DE, Czyzewicz G, Spigel DR, Crino L, Eberhardt WEE, Li A, Marimuthu S, Brahmer J. Five-Year Outcomes From the Randomized, Phase III Trials CheckMate 017 and 057: Nivolumab Versus Docetaxel in Previously Treated Non-Small-Cell Lung Cancer. J Clin Oncol. 2021 Mar 1;39(7):723-733. doi: 10.1200/JCO.20.01605. Epub 2021 Jan 15.

  PMID: 33449799 BACKGROUND

• Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, Timmerman JM, Collins GP, Ramchandren R, Cohen JB, De Boer JP, Kuruvilla J, Savage KJ, Trneny M, Shipp MA, Kato K, Sumbul A, Farsaci B, Ansell SM. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018 May 10;36(14):1428-1439. doi: 10.1200/JCO.2017.76.0793. Epub 2018 Mar 27.

  PMID: 29584546 BACKGROUND

• Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. doi: 10.1016/S0140-6736(20)31366-0. Epub 2020 Sep 1.

  PMID: 32888407 BACKGROUND

MeSH Terms

Interventions

dornase alfa

Study Officials

• Ron Ram, Prof.

  Sourasky Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ron Ram, Prof.

CONTACT

972-3-6973782; ronr@tlvmc.gov.il

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: CLS-015 (Dornase Alpha; DFF) is a recombinant human DNase I (rhDNase I), designed to degrade NETs both at the tumor tissue and in systemic blood circulation. CLS-015 increases performance of anti-CD19 CAR-T therapy

Study Record Dates

• First Submitted: January 4, 2026
• First Posted: January 22, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-01

Locations

IL (1)