Dynamic Individualized Risk Profiling of Patients With Relapsed/Refractory Lymphoid Malignancies and CD19-CAR T Cell Therapy (INTeRCePT 2.0)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Feasibilty of INTeRCePT assay
研究概览
简要总结
The INTeRCePT 2 study aims to develop a predictive assay to determine which patients with B cell lymphoma are most likely to respond to CAR T cell therapy. This assay combines five components for longitudinal profiling of each patient. The goal of the trial is that the assay can be completed (feasibility). This comprehensive assay integrates five key components including circulating tumor DNA (CAPPseq), inflammation markers from peripheral blood tests (InflaMIX), PET CT imaging parameters, immune cell profiles (flow cytometry), and performance status (ECOG). Ultimately, this tool could improve treatment selection, and guide more personalized therapy decisions for lymphoma patients receiving CAR T cells.
详细描述
Anti-CD19 CAR T-cell therapy is the new standard therapy for patients with relapsed/refractory aggressive B-cell lymphoma and transformed cure rates. The majority of patients fail treatment within the first 90 days. These results indicate a high medical need to optimize therapy e.g. by intensification for patients with high-risk of relapse after CD19-redirected CAR T cell therapy. INTeRCePT 2.0 is a feasibility study with application of a dynamic individualized risk profiling for prediction and early detection of high-risk constellation of patients post anti-CD19 CAR T-cell therapy.
We aim to develop tools to predict therapy failure earlier to provide appropriate therapy early post CAR T application in future studies.
Primary objective: Complete risk profiling (INTeRCePT assay) post-CAR T infusion (Arm A and B)(feasibility) Primary endpoint: Rate of complete INTeRCePT assay risk profiling post-CAR T infusion (Arm A and B) Co-primary objective: Complete risk profiling (INTeRCePT assay) by day 38 post-CAR T infusion (Arm A) Co-primary endpoint: Rate of complete INTeRCePT assay risk profiling by day 38 post-CAR T infusion (Arm A)
The primary variable of interest (primary endpoint and co-primary endpoint) of the study is the rate of complete INTeRCePT assay risk profiling by 38 days post-CAR-T cell infusion. These variables were selected as they directly measure the feasibility and timeliness of obtaining a full molecular risk profile within the critical time window post-infusion. This early risk assessment is key for future intervention in the window of opportunity for curation (low lymphoma load, CAR T cells still present in high numbers). In this study, clinical decisions are not influenced by the INTeRCePT assay results, but the study tests if the assay is completed and thus provides the basis for future (interventional) trials.
The secondary objectives will evaluate the predictive value of the INTeRCePT assay. The key secondary endpoint will be the rate of accurate prediction of complete response (CR vs. no CR) by 3 months post-CAR T-cell infusion. CR is defined as complete remission 3 months post CAR T cell therapy without the need for additional cancer-directed treatment. The accuracy of the INTeRCePT assay will be measured based on true positive and true negative rates, with a threshold of at least 80% predictive accuracy.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent before registration and prior to any trial specific procedures
- •Participants ≥ 18 years of age
- •Diagnosis of relapse/refractory B-cell lymphoma according to WHO 2022 classification
- •Measurable disease per response criteria specific to the disease e.g. per Lugano 2014 criteria
- •Patients planned for CD19-redirected CAR T cell therapy according to clinical standard of care
- •Patients who are willing to donate peripheral blood and biopsy material at indicated clinical visits
排除标准
- •Any condition, which precludes initiation of CD19-redirected CAR T cell therapy (e.g. breast feeding, pregnancy, infections, etc.) as judged by the treating physician
- •Any coexisting medical or psychological condition that would preclude participation in the required study procedures, as judged by the treating physician
- •Unwillingness or inability to comply with the protocol
研究组 & 干预措施
CAR T cell therapy-treated patients
Included are patients with relapsed/refractory lymphoid malignancies, treated with CD19-CAR T cell therapy.
结局指标
主要结局
Feasibilty of INTeRCePT assay
时间窗: From enrollment until day28 post CAR T Infusion
Risk profiling is performed by the INTeRCePT assay, which is a combinatorial, in-depth analysis of disease load (Liquid Biopsy, PET-CT/-MRI), immune environment "fitness" (scCytometry), performance status (ECOG) and inflammation status (InflaMix). The primary endpoint is the rate of successful completion of the INTeRCePT assay by day 38 post CAR T infusion (% of patients with complete INTeRCePT assay).
次要结局
- Rate of accurate prediction of complete response (CR vs. no CR) at month 3 post-CAR T infusion by the INTeRCePT assay(From enrollment until 3 months post CAR T cell infusion)