A Phase Ib/II Exploratory Clinical Trial of Memory-Enhanced 7×19-THEMIS CAR-T Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma

NCT07788118 | Recruiting Phase 1

• 1 other identifier: 2026-0675
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This study is aimed to explored the safety and efficacy of 7×19-THEMIS CAR-T cell therapy for large B-cell lymphoma and to conduct an exploratory comparison of the 3-month objective response rate (ORR) and complete remission rate (CR rate) between the experimental cohort and the historical control cohort (NCT04833504).

Conditions

Relapsed/Refractory Large B-cell Lymphoma (LBCL); Diffuse Large B-Cell Lymphoma (DLBCL); Primary Mediastinal Large B-cell Lymphoma (PMBCL); Transforming Follicular Lymphoma (tFL); Mantle Cell Lymphoma (MCL)

Outcome Measures

Primary Outcomes (3)

• Determination of the Recommended Phase II Dose (RP2D)

  Based on the incidence of DLTs, CAR-T cell kinetics, preliminary efficacy, and safety data from the Phase Ib dose-escalation phase, the Safety Review Committee (SRC) determined the RP2D following a comprehensive evaluation.

  Up to 3 months

• Objective Response Rate (ORR)

  At 3 months (±7 days) after infusion, the proportion of patients achieving complete remission (CR) or partial remission (PR) was assessed according to the Lugano 2014 criteria, and a descriptive comparison was made with the historical control cohort.

  Up to 3 months

• Complete Remission Rate (CR Rate)

  At 3 months (±7 days) after infusion, the proportion of patients who achieved complete remission (CR) was assessed according to the Lugano 2014 criteria, and a descriptive comparison was made with the historical control cohort.

  Up to 3 months

Secondary Outcomes (9)

• Incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) graded according to ASTCT 2019 criteria

  up to 28 days

• Incidence and duration of Grade ≥3 hematologic toxicities assessed according to CTCAE version 5.0

  up to 28 days

• Incidence of clinically significant infections requiring anti-infective treatment or hospitalization

  up to 28 days

• Progression-Free Survival (PFS)

  up to 2-5 years

• Overall Survival (OS)

  up to 2-5 years

Other Outcomes (4)

• Single-Cell Functional Characterization of CAR-T Products

  day-5, day4, day7, day11, day14, day18, day21, day28, month2

• Spearman correlation between memory T-cell subset proportions in the CAR-T infusion product and 3-month complete response

  day-5, day4, day7, day11, day14, day18, day21, day28, month3

• Trends in Anti-CAR Antibodies (ADA)

  day-5, day4, day7, day11, day14, day18, day21, day28, month3,month6,month12, year2 and year5

Study Arms (1)

7×19-THEMIS CAR-T

EXPERIMENTAL

A single dose intravenous injection of 7X19-Themis at day 0

Biological: 7×19-THEMIS CAR-T cells

Interventions

7×19-THEMIS CAR-T cells BIOLOGICAL

IL7 and CCL19 Armed anti-CD19 CAR-T with coexpressing Themis

7×19-THEMIS CAR-T

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntarily participate in this study and sign the informed consent form.
• Age range: 18 - 75 years old. Gender is not restricted.
• Histologically confirmed large B-cell lymphoma, including: diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma (PMBCL), transformed follicular lymphoma (tFL), and mantle cell lymphoma (MCL).
• CD19-positive (as determined by immunohistochemistry or flow cytometry; based on the most recent tumor biopsy results).
• Definition of relapsed/refractory: Failure to achieve complete remission (CR) after at least two lines of therapy (which must include a CD20 monoclonal antibody and an anthracycline); or disease progression during any course of treatment; or relapse/progression within 12 months after autologous hematopoietic stem cell transplantation.
• At least one measurable lesion: any lymph node lesion with a longest dimension \>1.5 cm, or any extranodal lesion with a longest dimension \>1.0 cm, and the lesion shows uptake on PET-CT (SUV greater than the hepatic pool).
• Absolute neutrophil count in peripheral blood ≥ 1,000/μL; platelet count ≥ 45,000/μL.
• Cardiac, hepatic, and renal function: creatinine \< 1.5 mg/dL; ALT/AST ≤ 2.5 times the upper limit of normal; total bilirubin \< 1.5 mg/dL; ejection fraction ≥ 50%.
• Possess sufficient cognitive capacity to voluntarily sign the informed consent form.
• Participants of reproductive potential must be willing to use effective contraception (from the time of signing the informed consent form until 12 months after CAR-T infusion).
• The investigator estimates a life expectancy of at least 4 months.
• Willing to comply with the schedule of visits, dosing regimen, laboratory tests, and other trial procedures.

You may not qualify if:

• History of other malignant tumors (excluding cured basal cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, etc.).
• Autologous hematopoietic stem cell transplantation within the past 6 weeks.
• Any targeted CAR-T therapy within 3 months prior to this CAR-T treatment.
• Patients who have previously received PD-1 monoclonal antibodies must have a washout period of ≥3 months before enrollment.
• Received cytotoxic drugs, glucocorticoids (except for prednisone-equivalent doses of ≤10 mg/day), or other targeted therapies within 2 weeks prior to cell collection.
• Active autoimmune diseases (e.g., systemic lupus erythematosus, inflammatory bowel disease, etc.).
• Uncontrolled active bacterial, fungal, or viral infections.
• HIV infection, syphilis; active hepatitis B or C: Hepatitis B: HBsAg-positive and HBV-DNA ≥ 1,000 IU/mL; Hepatitis C: HCV RNA-positive and abnormal liver function.
• Known central nervous system lymphoma (confirmed by brain MRI or CT and cerebrospinal fluid examination).

Sponsors & Collaborators

• Second Affiliated Hospital, Zhejiang University, School of Medicine: lead

Study Sites (1)

The Second Affiliated Hospital,School of Medicine,Zhejiang University, Hangzhou, Zhejiang 310009

Hangzhou, Zhejiang, 310009, China

RECRUITING

MeSH Terms

Conditions

Recurrence; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Wenbin Qian,Professor

  Second Affiliated Hospital, Zhejiang University, School of Medicine

  STUDY CHAIR

Central Study Contacts

Wenbin Qian,Professor

CONTACT

+86 13605801032; qianwb@zju.edu.cn

Wen Lei,Doctor

CONTACT

+86 18258448016; leiwen2017@zju.edu.cn

Study Design

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

Study Record Dates

• First Submitted: August 12, 2026
• First Posted: August 26, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2029
• Study Completion (Estimated): September 1, 2031
• Last Updated: August 26, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)