Combination of CAR-T therapy with other treatments for relapsed B-cell lymphoma

A Phase II Study of BTKi+Radiotherapy±Chemotherapy Bridging Before Chimeric Antigen Receptor T-cell Immunotherapy (CAR-T) in Combination With BTKi±PD-1 Inhibitor Maintenance Therapy for Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma (r/r B-NHL)

This study is testing whether combining CAR-T therapy with other treatments can help people with relapsed B-cell lymphoma feel better and achieve remission.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT05871684 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining CAR-T cell therapy with tyrosine kinase inhibitors or immune checkpoint inhibitors in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. The study aims to evaluate the objective remission and complete remission rates of this combination therapy, as well as its safety profile. Participants will receive CAR-T infusion alongside these additional therapies to enhance treatment outcomes. The trial will include patients who have not previously undergone CAR-T therapy and who meet specific eligibility criteria.

Who should consider this trial

Good fit: Ideal candidates are adults with relapsed or refractory B-cell non-Hodgkin's lymphoma who have not received prior CAR-T therapy.

Not a fit: Patients who have undergone allogeneic stem cell transplantation or have a history of certain neurological conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve remission rates for patients with difficult-to-treat B-cell lymphoma.

How similar studies have performed: Previous studies have shown promising results with similar combinations of CAR-T therapy and other treatments, indicating potential for success in this trial.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed diagnosis of B-cell non-Hodgkin's lymphoma; and according to the 2014 Lugano diagnostic criteria.
* Patients who have relapsed or are refractory to at least prior first-line therapy, including anthracycline-containing chemotherapy regimens and anti-CD20 monoclonal antibody therapy; patients must meet the definitions of refractory and relapsed.
* No prior CD19 CAR-T cell therapy
* Adequate organ function to receive CAR-T cell therapy
* Vascular condition adequate to perform leukapheresis
* Able to provide written informed consent (ICF) and able to understand and agree to comply with the study requirements and assessment schedule
* Patients of childbearing potential must be willing to use highly effective contraception for the duration of the study, and for 120 days after the last dose of treatment.
* ECOG 0-2

Exclusion Criteria:

* History of allogeneic hematopoietic stem cell transplantation;
* History of epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease or any autoimmune disease involving the central nervous system;
* Presence or current concurrent other malignancies within the past 2 years, with the exception of cured cervical carcinoma in situ, non-melanoma skin cancer and superficial bladder tumors (Ta (non-invasive tumors), Tis (carcinoma in situ) and T1 (tumor infiltrating basement membrane));
* Serious cardiovascular disease: grade II or higher myocardial ischemia or myocardial infarction, poorly controlled arrhythmias; grade III-IV cardiac insufficiency by NYHA criteria, or cardiac ultrasound suggestive of left ventricular ejection fraction (LVEF) \<50%;
* Hypersensitivity to any study drug or excipient;
* Patients with active viral hepatitis requiring treatment as determined by the investigator: chronic hepatitis B virus carriers with HBV DNA ≥ 500 IU/mL (2500 copies/mL) (HBV DNA testing only for patients who test positive for hepatitis B surface antigen or core antibody); patients who test positive for HCV RNA (HCV testing only for patients who test positive for hepatitis C virus antibody) RNA testing);
* Patients with any active autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism), or a known history of allogeneic organ transplantation, or long-term heavy use of hormones or use of other immunomodulatory agents, or other patients assessed by the investigator as having implications for study treatment ;
* The presence of an active infection;
* History of uncontrollable systemic disease, including diabetes, hypertension, acute lung disease, etc;
* Known human immunodeficiency virus (HIV) infection;
* Presence of an underlying medical condition or alcohol/drug abuse or dependence that is detrimental to study drug administration, or that may affect interpretation of results, or that places the patient at high risk of developing treatment complications;
* Organ damage due to an autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) or the need for systemic application of immunosuppressive or other systemic disease-controlling drugs within the past 2 years.

Where this trial is running

Shanghai

• Ruijin Hospital, Shanghai Jiao Tong University School of Medicine — Shanghai, China (Recruiting)

Study contacts

• Study coordinator: Weili Zhao, Doctor

Conditions Diffuse Large B Cell Lymphoma