Comparing immunotherapy bridging treatment to standard therapy in low-risk B-NHL patients

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

This study is testing whether adding an immunotherapy treatment with zanubrutinib helps people with low-risk B-cell non-Hodgkin lymphoma feel better compared to those who don’t get this extra treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 144 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ruijin Hospital (other)
• Drugs / interventions: CAR T, CAR-T, chemotherapy, immunotherapy, zanubrutinib
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06695013 on ClinicalTrials.gov

What this trial studies

This study investigates the effectiveness of adding immunotherapy bridging treatment using zanubrutinib and potentially radiotherapy for patients with low-risk refractory or relapsed B-cell non-Hodgkin lymphoma (B-NHL). Participants will be divided into two groups: one receiving the bridging treatment and the other not receiving any bridging medications. The study will assess treatment outcomes based on the patients' responses at 28 days, determining subsequent maintenance therapy for those with partial responses. The goal is to identify the most effective treatment strategy for this patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 or older with histologically confirmed low-risk refractory or relapsed B-NHL who have not previously undergone CD19 CAR T cell therapy.

Not a fit: Patients with stable disease or disease progression, as well as those with a history of allogeneic hematopoietic stem cell transplantation, will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved treatment outcomes for low-risk B-NHL patients.

How similar studies have performed: While this study explores a novel approach, similar studies have shown promise in enhancing treatment outcomes with bridging therapies in hematological malignancies.

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.

Where this trial is running

Shanghai, Shanghai Municipality

• Ruijin — Shanghai, Shanghai Municipality, China (RECRUITING)

Study contacts

• Study coordinator: zhao wei li, doctor Degree

Conditions: B-NHL, CART Therapy, Zanubrutinib, maintenance