Immunobridging/Maintenance Therapy Versus Non-bridging Therapy in CAR-T Therapy for Low-risk R/R B-NHL (CART R/R NHL)

Shanghai Jiao Tong University

Status and phase: Enrolling; Phase 2

Conditions: B-NHL; CART Therapy

Treatments: Radiation: Bridging radiotherapy; Drug: zanubrutinib; Drug: Tislelizumab; Drug: CAR-T

Study type: Interventional

Funder types: Other

Identifiers

NCT06695013

CLMB study

Details and patient eligibility

About

This study aims to explore whether adding immunotherapy bridging treatment for low-risk refractory/relapsed B-NHL can demonstrate better outcomes, in order to find the most effective treatment plan for low-risk patients.

Full description

In the immunotherapy bridging treatment group, zanubrutinib ± radiotherapy will be used as the bridging treatment regimen, while those without bridging treatment will not receive bridging medications. Both groups will determine subsequent maintenance treatment based on efficacy at D28. Patients achieving complete response (CR) will not receive maintenance therapy, while those with partial response (PR) will be given oral zanubrutinib + PD-1 inhibitor for 2 years. Patients with stable disease (SD) or disease progression (PD) will not be included in this study.

Enrollment: 144 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

1. Age 18 or older, regardless of gender.
2. Histologically confirmed B-cell non-Hodgkin lymphoma, according to Lugano diagnostic criteria.
3. At least first-line treatment for relapsed or refractory patients, including chemotherapy regimens containing anthracyclines and anti-CD20 monoclonal antibody therapy; patients must meet definitions of refractory and recurrent.
4. No prior CD19 CAR T cell therapy.
5. Adequate organ function to assess tolerance to CAR-T therapy.
6. Sufficient vascular access for leukapheresis.
7. Ability to provide written informed consent and understand the study requirements and evaluation schedule.
8. Fertile patients must agree to use highly effective contraception during the study and for 120 days post-treatment.

Exclusion criteria：

Patients with any of the following conditions will not be included in the study:

1. History of allogeneic hematopoietic stem cell transplantation.
2. History of epilepsy, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system.
3. Any other malignancies within the past 2 years, except for cured cervical carcinoma in situ, non-melanoma skin cancer, and superficial bladder tumors (Ta, Tis, and T1).
4. Severe cardiovascular disease: NYHA grade II or above myocardial ischemia or myocardial infarction, poorly controlled arrhythmias; NYHA grade III to IV heart failure or left ventricular ejection fraction (LVEF) < 50%.
5. Allergy to any investigational drug or excipient.
6. Active viral hepatitis requiring treatment, including chronic HBV carriers with HBV DNA ≥ 500 IU/mL and positive HCV RNA.
7. Active autoimmune disease or known history of allogeneic organ transplantation; long-term heavy use of immunosuppressants or other factors affecting study therapy.
8. Active infection.
9. History of uncontrolled systemic disease, such as diabetes or hypertension.
10. Known HIV infection.
11. Underlying medical condition or substance abuse that may interfere with drug administration or affect result interpretation, or increase treatment risk.
12. End-organ damage from autoimmune disease within the past 2 years or systemic use of immunosuppressive drugs.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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144 participants in 2 patient groups

Immunotherapy bridging treatment

Experimental group

Description:

Zanubrutinib ± radiotherapy was used as the bridging therapy in the immunobridging treatment group, a Follow-up maintenance treatment was determined according to the efficacy of D28 in the two groups. Patients with complete response (CR) were given no maintenance treatment, while patients with partial response (PR) were given Zanubrutinib orally plus PD-1 inhibitor for 2 years. Patients with stable SD or progressive PD were excluded from this study

Treatment:

Drug: CAR-T

Drug: Tislelizumab

Drug: zanubrutinib

Radiation: Bridging radiotherapy

no bridging treatment

Active Comparator group

Description:

The control group will not receive bridging treatment. Maintenance treatment will be consistent with the experimental group.

Treatment:

Drug: CAR-T

Drug: Tislelizumab

Drug: zanubrutinib