Patients With Large B-cell Lymphoma Receiving CAR-T Cell Therapy
Conditions
Keywords
Large B-cell lymphoma, Diammonium Glycyrrhizinate, CAR-T cell therapy, Toxicity reducing and efficacy enhancing
Brief summary
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?
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.
Interventions
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).
Sponsors
Tongji Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Intervention model description
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). For the control group, after CAR-T cell infusion, standard clinical care is provided without additional diammonium glycyrrhizinate intervention.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CRS | Within 28 days post CAR-T cell infusion | CRS incidence and incidence of grade ≥3 CRS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete remission rate | Assessments are performed every 3 months within the first two years after CAR-T infusion | 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. |
| Objective Response Rate | Assessments are performed every 3 months within the first two years after CAR-T infusion | 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. |
| Duration of response | Assessments are performed during the first two years following CAR-T infusion. | 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. |
| Overall survival | Up to 2 years as per long-term follow-up mentions | The time from confirmed diagnosis to death from any cause. |
| Progression-free survival | Assessments are performed during the first two years following CAR-T infusion | The time interval from the start of treatment to tumor progression (PD) or death from any cause. |
| Level of CAR-T cell persistence | Assessments are performed every 3 months within the first year after CAR-T infusion | Duration of CAR-T cell persistence in patients |
| Adverse events | Assessments are performed during the first two years following CAR-T infusion | Adverse events following CAR-T cell infusion |
Contacts
CONTACTJia Wei
PRINCIPAL_INVESTIGATORJia Wei
Tongji Hospital
Outcome results
None listed