Study on the Effect of Oral Diammonium Glycyrrhizinate in Attenuating Toxicity and Enhancing Efficacy of CAR-T Cell Therapy

A Single-Center, Prospective, Randomized Controlled Clinical Study of Oral Diammonium Glycyrrhizinate for Attenuating Toxicity and Enhancing Efficacy of CAR-T Cell Therapy

The purpose of this study is to evaluate the effect of oral diammonium glycyrrhizinate in reducing toxicity and enhancing efficacy of CAR-T cell therapy in patients with large B-cell lymphoma. Two main questions are addressed: 1) Can oral diammonium glycyrrhizinate reduce the incidence and severity of CRS induced by CAR-T cells? 2) Can oral diammonium glycyrrhizinate synergistically increase the therapeutic efficacy of CAR-T cell therapy?

Study Overview

• Status: Not yet recruiting
• Conditions: Patients With Large B-cell Lymphoma Receiving CAR-T Cell Therapy
• Intervention / Treatment: Drug: Diammonium glycyrrhizinate Capsules

Detailed Description

Current studies suggest that regulating pyroptosis may play a role in reducing toxicity and enhancing efficacy during CAR-T cell therapy by alleviating cytokine release syndrome (CRS) and improving the tumor microenvironment (TME). Glycyrrhizic acid has been clearly shown to inhibit pyroptosis and is widely recognized for its broad-spectrum anti-inflammatory effects and ability to improve the TME. Therefore, it holds promise as an ideal intervention for preventing/treating CRS induced by CAR-T cells and for synergistically enhancing the therapeutic efficacy of CAR-T cell therapy. Accordingly, this study aims to investigate the effect of oral diammonium glycyrrhizinate in reducing toxicity and enhancing efficacy of CAR-T cell therapy in patients with large B-cell lymphoma.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jia Wei; Phone Number: 027-83663200; Email: jiawei@tjh.tjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years.
2. Patients diagnosed with large B-cell lymphoma and receiving CAR-T cell therapy.
3. Adequate organ function prior to enrollment: ALT and AST ≤ 2.5 × ULN (upper limit of normal); may be extended to ≤5 × ULN in patients with liver involvement; serum total bilirubin < 34 μmol/L; creatinine clearance > 30 mL/min; cardiac ejection fraction (EF) ≥ 40%, with no pericardial effusion or significant arrhythmia; room air SpO₂ ≥ 92%.
4. No central nervous system involvement of lymphoma confirmed by MRI prior to enrollment.
5. Subjects of childbearing potential must agree to use highly effective contraceptive methods.
6. The subject or their legal guardian must be able to understand and voluntarily sign a written informed consent form.

Exclusion Criteria:

1. Presence of a prior malignancy (other than the disease under study) that requires ongoing systemic treatment for any other malignant tumor.
2. Presence of any life-threatening disease, medical condition, or organ system dysfunction that, in the investigator's judgment, may compromise patient safety or interfere with the interpretation of safety or efficacy data.
3. Current or prior central nervous system (CNS) involvement by malignancy.
4. Receipt of allogeneic stem cell transplantation within 6 months prior to enrollment, or autologous stem cell transplantation within 3 months prior to enrollment; and the patient must have no signs or symptoms of graft-versus-host disease and must not be receiving immunosuppressive therapy.
5. Intolerance or allergy to glycyrrhizic acid preparations.
6. Patient refuses to comply with the study requirements to complete the research work.
7. In the investigator's judgment, the patient is unable to complete the study or comply with the study requirements (due to administrative reasons or other reasons), or is considered unsuitable for clinical trial participation for other reasons.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental group; At the time of CAR-T cell infusion, oral diammonium glycyrrhizinate is given in addition to standard clinical care (first two weeks: 150 mg three times daily; thereafter, 100 mg once daily, continued orally for 2 years).	Drug: Diammonium glycyrrhizinate Capsules; For the experimental group, at the time of CAR-T cell infusion, oral diammonium glycyrrhizinate is given in addition to standard clinical care (first two weeks: 150 mg three times daily; thereafter, 100 mg once daily, continued orally for 2 years).
No Intervention: Control group; For the control group, after CAR-T cell infusion, standard clinical care is provided without additional diammonium glycyrrhizinate intervention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CRS	CRS incidence and incidence of grade ≥3 CRS	Within 28 days post CAR-T cell infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete remission rate	Proportion of participants achieving Complete Response (CR) at the end of treatment. Efficacy is evaluated by both investigators and independent imaging personnel based on PET-CT or CT.	Assessments are performed every 3 months within the first two years after CAR-T infusion
Objective Response Rate	Objective Response Rate(ORR) is defined as the proportion of subjects achieving complete remission(CR) and partial response(PR). Efficacy is evaluated by both investigators and independent imaging personnel based on PET-CT or CT.	Assessments are performed every 3 months within the first two years after CAR-T infusion
Duration of response	Time from documentation of tumor response (CR or PR) to disease progression or death. Efficacy is evaluated by both investigators and independent imaging personnel based on PET-CT or CT.	Assessments are performed during the first two years following CAR-T infusion.
Overall survival	The time from confirmed diagnosis to death from any cause.	Up to 2 years as per long-term follow-up mentions
Progression-free survival	The time interval from the start of treatment to tumor progression (PD) or death from any cause.	Assessments are performed during the first two years following CAR-T infusion
Level of CAR-T cell persistence	Duration of CAR-T cell persistence in patients	Assessments are performed every 3 months within the first year after CAR-T infusion
Adverse events	Adverse events following CAR-T cell infusion	Assessments are performed during the first two years following CAR-T infusion

Collaborators and Investigators

• Sponsor: Tongji Hospital
• Investigators: Principal Investigator: Jia Wei, Tongji Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 22, 2026
• Primary Completion (Estimated): May 31, 2029
• Study Completion (Estimated): May 31, 2030

Study Registration Dates

• First Submitted: May 21, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 1, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: CAR-T cell therapy; Large B-cell lymphoma; Diammonium Glycyrrhizinate; Toxicity reducing and efficacy enhancing
• Additional Relevant MeSH Terms: Organic Chemicals; Hydrocarbons; Terpenes; Pentacyclic Triterpenes; Triterpenes; Glycyrrhizic Acid
• Other Study ID Numbers: TJ-IRB202603111

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No