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

NCT06695013 | Recruiting Phase 2 DMC

• 1 other identifier: CLMB study
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

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.

Conditions

B-NHL; CART Therapy

Keywords

Zanubrutinib; maintenance

Outcome Measures

Primary Outcomes (1)

• Complete response rate(CRR) at 3-month

  Complete response rate at 3-month is defined as the incidence of subjects achieving complete response (CR) at 3-month after CAR-T infusion according to the Lugano Classification, as determined by study investigators.

  3 months post CAR-T infusion

Secondary Outcomes (7)

• Complete response rate(CRR) on D28

  28 days post CAR-T infusion

• Objective remission rate (ORR) on D28

  28 days post CAR-T infusion

• Objective remission rate (ORR) at 3-month

  3 months post CAR-T infusion

• Progression-Free Survival (PFS)

  2 years post CAR-T infusion

• Overall Survival (OS)

  2 years post CAR-T infusion

Study Arms (2)

Immunotherapy bridging treatment

EXPERIMENTAL

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

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

no bridging treatment

ACTIVE COMPARATOR

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

Drug: zanubrutinib; Drug: CAR-T; Drug: Tislelizumab

Interventions

zanubrutinib DRUG

zanubrutinib 160 mg BID orally

Immunotherapy bridging treatment; no bridging treatment

CAR-T DRUG

CAR-T Cell therapy

Immunotherapy bridging treatment; no bridging treatment

Bridging radiotherapy RADIATION

For patients in the experimental group, the decision regarding radiotherapy will depend on whether the specific lesions are suitable.

Immunotherapy bridging treatment

Tislelizumab DRUG

200mg IV Q3-4W

Immunotherapy bridging treatment; no bridging treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 or older, regardless of gender.
• Histologically confirmed B-cell non-Hodgkin lymphoma, according to Lugano diagnostic criteria.
• 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.
• No prior CD19 CAR T cell therapy.
• Adequate organ function to assess tolerance to CAR-T therapy.
• Sufficient vascular access for leukapheresis.
• Ability to provide written informed consent and understand the study requirements and evaluation schedule.
• Fertile patients must agree to use highly effective contraception during the study and for 120 days post-treatment.

You may not qualify if:

• Patients with any of the following conditions will not be included in the study:
• History of allogeneic hematopoietic stem cell transplantation.
• History of epilepsy, cerebrovascular ischemia/bleeding, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system.
• 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).
• 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%.
• Allergy to any investigational drug or excipient.
• Active viral hepatitis requiring treatment, including chronic HBV carriers with HBV DNA ≥ 500 IU/mL and positive HCV RNA.
• Active autoimmune disease or known history of allogeneic organ transplantation; long-term heavy use of immunosuppressants or other factors affecting study therapy.
• Active infection.
• History of uncontrolled systemic disease, such as diabetes or hypertension.
• Known HIV infection.
• Underlying medical condition or substance abuse that may interfere with drug administration or affect result interpretation, or increase treatment risk.
• End-organ damage from autoimmune disease within the past 2 years or systemic use of immunosuppressive drugs.

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin

Shanghai, Shanghai Municipality, China

RECRUITING

MeSH Terms

Interventions

zanubrutinib; tislelizumab

Central Study Contacts

zhao wei li, doctor Degree

CONTACT

+862164370045; zwl_trial@163.com

yan zi xun, doctor degree

CONTACT

+862164370045; yzx12119@rjh.com.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 31, 2024
• First Posted: November 19, 2024
• Study Start: November 20, 2024
• Primary Completion (Estimated): November 20, 2026
• Study Completion (Estimated): March 20, 2027
• Last Updated: January 24, 2025

Record last verified: 2025-01

Locations

CN (1)