Clinical trial NCT06695013: Immunobridging/Maintenance Therapy Versus Non-bridging Therapy in CAR-T Therapy for Low-risk R/R B-NHL
Official title: Immunobridging/Maintenance Therapy Versus Non-bridging Therapy in CAR-T Therapy for Low-risk Relapsed/Refractory B Cell Non-Hodgkin Lymphoma(R/R B-NHL): A Multicenter, Prospective, Randomized, Open-label, Controlled Clinical Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: B-NHL
CART Therapy
Keywords: Zanubrutinib
maintenance
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2024-11-19
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: Complete response rate(CRR) at 3-month
timeFrame: 3 months post CAR-T infusion
Secondary outcomes:
measure: Complete response rate(CRR) on D28
timeFrame: 28 days post CAR-T infusion
measure: Objective remission rate (ORR) on D28
timeFrame: 28 days post CAR-T infusion
measure: Objective remission rate (ORR) at 3-month
timeFrame: 3 months post CAR-T infusion
measure: Progression-Free Survival (PFS)
timeFrame: 2 years post CAR-T infusion
measure: Overall Survival (OS)
timeFrame: 2 years post CAR-T infusion
measure: CAR-T cell expansion
timeFrame: 2 years post CAR-T infusion
measure: Adverse Events rate
timeFrame: 2 years post CAR-T infusion
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin
state: Shanghai
Study officials:
References: