Clinical trial NCT05871684: A Combination Study of CAR-T Therapy in r/r B-NHL
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Diffuse Large B Cell Lymphoma
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
First posted: 2023-05-23
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: In registry studies of CAR-T products that have been marketed globally, patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (r/r B-NHL) have been enrolled to receive CAR-T infusion in combination with tyrosine kinase inhibitors (BTKi) or immune checkpoint inhibitors (PD-1 or PD-L1 antibodies), with objective remission rate (ORR) for CAR-T in combination with BTKi ranging from 83.3%-100% and complete remission rate (CRR) were 33.3-75%. The ORRs for objective remission rates for CAR-T combined with PD1/PD-L1 ranged from 50-91% and CRRs were 33.3-64%, respectively. With regard to safety, no dose-limiting toxic (DLT) occurred and the incidence of other adverse reactions was low, and studies demonstrated that BTKi or PD-1/PD-L1 antibodies could further enhance the responsiveness and durability of anti-CD19 CAR-T cell therapy. However, there are no studies exploring the efficacy and safety of clinical regimens using BTKi + radiotherapy ± chemotherapy as a bridging regimen to treat r/r B-NHL in combination with BTKi and/or PD-1 inhibitor after CAR-T cell infusion. In real-world applications of commercial CAR-T, CAR-T therapy combined with BTKi or PD-1/PD-L1 antibodies may further improve response rates and remission persistence in r/r B-NHL patients receiving CAR-T infusion back, with efficacy benefits while ensuring a manageable safety profile. Therefore, our center plans to conduct a phase II clinical study of Regent CAR-T 001(A phase II study of BTKi+radiotherapy±chemotherapy bridging before CAR-T cell therpay in combination with BTKi±PD-1 inhibitor for r/r B-NHL).


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.

Primary outcomes:
measure: 3-month complete response rate
timeFrame: 3-months after CAR-T infusion
Secondary outcomes:
measure: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0
timeFrame: End of treatment visit (2 years after CAR-T cell infusion)
measure: 1-month objective response rate
timeFrame: 1 month after CAR-T infusion
measure: Progression-free survival
timeFrame: End of treatment visit (2 years after CAR-T cell infusion)
measure: Overall survival
timeFrame: End of treatment visit (2 years after CAR-T cell infusion)
measure: Time to reponse
timeFrame: End of treatment visit (2 years after CAR-T cell infusion)
measure: Duration of response
timeFrame: End of treatment visit (2 years after CAR-T cell infusion)
measure: Peak Plasma Concentration (Cmax)
timeFrame: End of treatment visit (2 years after CAR-T cell infusion)
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: 28 days after infusion
measure: Time to Peak Plasma Concentration (Tmax)
timeFrame: End of treatment visit (2 years after CAR-T cell infusion)
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Study officials:
References: