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)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- 3-month complete response rate
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
The combination treatment group of CAR-T therapy
Patients dicided to receive CAR-T cell therapy will be divided into groups A and B according to their tumor burden. Group A was given a bridging regimen of BTKi (160 mg b.i.d. p.o.) + radiotherapy + chemotherapy, and group B was given a bridging regimen of BTKi (160 mg b.i.d. p.o.) + radiotherapy; BTKi (160 mg b.i.d. p.o.) was given continuously from D1 to D28 after the return of CAR-T after infusion; Based on the results of the first evaluation on day 28 after CAR-T cell infusion, CR patients were divided into groups A1 and B1, and both groups were given BTKi (160 mg b.i.d. p.o.) for 3 months maintenance; PR patients were divided into groups A2 and B2, and both groups were given BTKi (160 mg b.i.d. p.o.) for 3 months maintenance and PD-1 inhibitor (200mg q3w i.v.) for 2 years maintenance;
干预措施: BTK inhibitor (Drug)
The combination treatment group of CAR-T therapy
Patients dicided to receive CAR-T cell therapy will be divided into groups A and B according to their tumor burden. Group A was given a bridging regimen of BTKi (160 mg b.i.d. p.o.) + radiotherapy + chemotherapy, and group B was given a bridging regimen of BTKi (160 mg b.i.d. p.o.) + radiotherapy; BTKi (160 mg b.i.d. p.o.) was given continuously from D1 to D28 after the return of CAR-T after infusion; Based on the results of the first evaluation on day 28 after CAR-T cell infusion, CR patients were divided into groups A1 and B1, and both groups were given BTKi (160 mg b.i.d. p.o.) for 3 months maintenance; PR patients were divided into groups A2 and B2, and both groups were given BTKi (160 mg b.i.d. p.o.) for 3 months maintenance and PD-1 inhibitor (200mg q3w i.v.) for 2 years maintenance;
干预措施: PD-1 inhibitor (Drug)
结局指标
主要结局
3-month complete response rate
时间窗: 3-months after CAR-T infusion
Percentage of participants with complete response at 3-months after CAR-T infusion determined on the basis of investigator assessments according to 2014 Lugano criteria.
次要结局
- 1-month objective response rate(1 month after CAR-T infusion)
- Overall survival(End of treatment visit (2 years after CAR-T cell infusion))
- Time to Peak Plasma Concentration (Tmax)(End of treatment visit (2 years after CAR-T cell infusion))
- Peak Plasma Concentration (Cmax)(End of treatment visit (2 years after CAR-T cell infusion))
- Progression-free survival(End of treatment visit (2 years after CAR-T cell infusion))
- Time to reponse(End of treatment visit (2 years after CAR-T cell infusion))
- Area under the plasma concentration versus time curve (AUC)(28 days after infusion)
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0(End of treatment visit (2 years after CAR-T cell infusion))
- Duration of response(End of treatment visit (2 years after CAR-T cell infusion))