Chimeric Antigen Receptor Natural Killer Cell Therapy for High-risk Lymphoma Patients With Primary Sjogren's Syndrome

NCT06967038 | Recruiting Phase 1

• 1 other identifier: Tongji Hospital, Shanghai
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a phase I-II clinical trial of CAR-NK cell therapy for high-risk lymphoma patients with primary Sjogren's syndrome (pSS). The aim is to determine the optimal dose of CAR-NK cells and evaluate the safety and efficacy of increasing doses of iC9/CAR19/IL15 CB-NK cell therapy. Use i3+3 based design to increase dosage. Dose limiting toxicity (DLT) is defined as the occurrence of CRS within 2 weeks after cell infusion, requiring transfer to the intensive care unit, or grade III-IV acute graft-versus-host disease within 40 days after infusion, or grade 3-5 allergic reactions related to CAR-NK cell infusion. For the purpose of i3+3 design, efficacy is defined as a reduction in the high-risk of lymphoma in pSS patients and at least partial relief of dry mouth and eye symptoms on the 30th day after CAR-NK cell infusion.

Conditions

Primary Sjogren's Syndrome; Lymphoma

Keywords

primary Sjogren's syndrome; lymphoma; CAR-NK; Dose limiting toxicity

Outcome Measures

Primary Outcomes (2)

• Safety: Incidence of Dose limiting toxicity (DLT)

  The dose escalation method adopts the i3+3 design, and CAR-NK cells are tentatively given three doses based on literature: 5×10\^6/kg body weight, 1×10\^7/kg body weight, and 5×10\^7/kg body weight. Plan to enroll 6-12 subjects. Researchers can together decide whether to increase it to a higher dose to determine the possible therapeutic dose. During the experiment, dosage adjustments can be made based on the safety and tolerability data of the subjects, including limiting toxicity type, incidence, and severity of dose limiting toxicity (DLT).

  45 days

• Safety: Incidence and severity of adverse events (AEs)

  One or more adverse events are related to CAR-NK cell therapy occurring in a subject within 45 days after the first infusion of CAR-NK cells. (1) Inflammatory cytokine release syndrome of grade ≥ 3 within 2 weeks. (2) Allergic reactions of grade 3 or higher within 2 weeks. (3) Organ damage of grade≥3 within 2 weeks (nerve, cardiovascular, lung, genitourinary, gastrointestinal, liver, skin, etc.). (4) Grade≥3 graft-versus-host disease within 45 days. (5) Deaths related to treatment within 45 days.

  45 days

Secondary Outcomes (4)

• cell treatment efficacy

  one year

• cell treatment efficacy

  one year

• cell treatment efficacy

  one year

• cell treatment efficacy

  one year

Study Arms (1)

CAR-NK

EXPERIMENTAL

CAR-NK cell therapy

Biological: CAR-NK cell

Interventions

CAR-NK cell BIOLOGICAL

Chimeric Antigen Receptor Natural Killer Cell

CAR-NK

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range of 18-70 years old, gender not limited;
• Diagnosed with primary Sjogren's syndrome, meeting the 2016 ACR/EULAR classification criteria;
• Persistent enlargement of salivary glands, lymph nodes, liver, or spleen (imaging/or pathology), and at least 2 of the following 4 conditions are met: ① Cryoglobulinemia; ② Low C4; ③ Decreased white blood cells; ④ Positive for anti SSA or anti SSB;
• Liver and kidney function, defined as S serum GPT\<3 times the upper limit of normal; Serum bilirubin and alkaline phosphatase are less than twice the upper limit of normal, and serum creatinine is ≤ 2mg/dl;
• Normal cognitive function and voluntarily participate in this clinical trial. Signing a written informed consent form. Can follow and complete all trial procedures.

You may not qualify if:

• Pregnant and lactating women;
• Patients with hepatitis B, hepatitis C, HIV and other virus infections;
• Highly allergic constitution or history of severe allergies;
• Patients with a history of other autoimmune diseases;
• Patients with severe heart failure, respiratory failure, liver dysfunction, kidney failure, persistent bleeding, malignant tumors, and diabetes insipidus;
• There are other situations where the researcher deems it inappropriate to participate in this clinical study.

Sponsors & Collaborators

• Bangdong Gong: lead

Study Sites (1)

Tongji Hospital of Tongji University

Shanghai, Shanghai Municipality, 200065, China

RECRUITING

MeSH Terms

Conditions

Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: associate chief physician

Study Record Dates

• First Submitted: April 22, 2025
• First Posted: May 13, 2025
• Study Start: February 28, 2025
• Primary Completion (Estimated): October 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: May 13, 2025

Record last verified: 2025-04

Locations

CN (1)