Development and Validation of a Patient-Reported Measure Assessing Chimeric Antigen Receptor (CAR) T-Cell Therapy-Related Side Effects

开发和验证患者报告的评估嵌合抗原受体 (CAR) T 细胞治疗相关副作用的方法

• 批准号: 10588154
• 负责人: Anna Barata
• 金额: $ 6.7万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-08 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10588154
• 关键词: Acute; Acute Lymphocytic Leukemia; Acute Myelocytic Leukemia; Address; Adult; Adverse event; Aftercare; Agitation; Attention; B-Cell Lymphomas; CAR T cell therapy; Cancer Patient; Caregivers; Caring; Categories; Chronic; Chronic Disease; Clinical; Clinical Trials; Collaborations; Common Terminology Criteria for Adverse Events; Cross-Sectional Studies; Data; Decision Making; Detection; Development; Diagnostic; Disease; Disorientation; Distress; Drowsiness; Ensure; Face; Family Caregiver; Family member; Future; Goals; Guidelines; Handwriting; Hematologic Neoplasms; Hematology; Impairment; In complete remission; Information Systems; Infusion procedures; Intervention Trial; Interview; Language; Late Effects; Learning; Libraries; Malignant Neoplasms; Malignant neoplasm of ovary; Maps; Measurement; Measures; Medical; Memory; Neurologic; Observational Study; Oncology; Outcome Measure; Patient Education; Patient Outcomes Assessments; Patients; Physicians; Population; Prognosis; Property; Provider; Psychometrics; Quality of life; Readability; Recommendation; Recovery; Refractory; Relapse; Reporting; Research; Risk; Sampling; Solid; Supportive care; Survivors; Symptoms; Testing; Therapeutic Trials; Toxic effect; Translating; Treatment Side Effects; Tremor; Validation; Vision; Writing; bilingualism; chimeric antigen receptor T cells; clinical care; cognitive interview; cytokine release syndrome; early phase trial; experience; improved; innovation; neurotoxicity; novel; novel therapeutics; response; side effect; success; survivorship; symptomatology; therapy outcome; tumor

PROJECT SUMMARY Chimeric antigen receptor (CAR) T-cell therapy is transforming care for adult patients with hematological malignancies who have otherwise poor prognoses. Up to 40% of patients with large B cell lymphoma (LBCL) can expect to survive at least two years after infusion of CAR T-cell therapy, in contrast to a mean overall survival of 6 months before the advent of CAR T-cell therapy. Moreover, many more trials are underway to evaluate CAR T-cell therapy for other hematologic and solid malignancies. As a result, there is an increasing population of survivors who experience the unique side effects associated with CAR T-cell therapy such as cytokine release syndrome (CRS) and neurotoxicity. Data on toxicities of CAR T-cell therapy come almost exclusively from physician-rated adverse events (AEs) on clinical trials. In contrast, patient-reported outcomes (PROs) provide important information from the patient’s perspective that is complementary to AEs. The FDA defines PROs as: 1) symptoms of disease, 2) side effects of treatment, and 3) quality of life. Although there are well-validated measures of symptoms of disease (#1) and quality of life (#3), there are no validated measures that capture the unique side effects of CAR T-cell therapy (#2). Lack of such a measure limits attempts to conduct research and patient education about this novel therapy. This study will develop and validate a new measure assessing patient- reported side effects of CAR T-cell therapy. Measure development will follow FDA measure development guidelines and be available in English and Spanish. In Aim 1, qualitative interviews will be conducted with 20 CAR T-cell recipients, 20 informal family caregivers, and 20 medical providers with expertise in CAR T-cell therapy. Patients and caregivers will be sampled across the survivorship trajectory to ensure adequate representation of a variety of experiences since CAR T-cell therapy. Qualitative interviews will identify patient- reported side effects that are common, severe, distressing, and diagnostically important over the course of CAR T-cell therapy, recovery and survivorship. Side effects will be mapped on to the Functional Assessment of Chronic Illness Therapy (FACIT) item library of 700 unique PRO items. New items will be written for side effects that do not have a corresponding FACIT item. In Aim 2, cognitive interviews with 20 additional patients will be conducted to ensure the readability, comprehensibility, and face validity of the item bank as well as generate additional items as needed. In Aim 3, convergent, divergent, and discriminant validity as well as reliability will be evaluated in a cross-sectional study assessing 150 CAR T-cell therapy patients at various times since treatment. The current project is highly innovative. From a research perspective, the measure will provide important data in observational, interventional, and therapeutic trials with CAR T-cell therapy recipients. From a clinical perspective, the measure will lead to a better detection of patient-reported side effects to improve supportive care for this population.

项目摘要 嵌合抗原受体（CAR）T细胞疗法正在为成年患者改造护理 否则预后不佳的恶性肿瘤。大量B细胞淋巴瘤（LBCL）的患者中，多达40％ 与平均总生存期相比 在汽车T细胞疗法冒险之前的6个月。此外，正在进行许多评估汽车的试验 用于其他血液学和固体恶性肿瘤的T细胞疗法。结果，人口越来越多 经历与汽车T细胞疗法相关的独特副作用（例如细胞因子释放）的幸存者 综合征（CRS）和神经毒性。有关汽车T细胞疗法毒性的数据几乎完全来自 临床试验的物理评分不良事件（AES）。相反，患者报告的结果（专业）提供 从患者的角度来看，重要信息是AES的完整信息。 FDA将优点定义为： 1）疾病症状，2）治疗的副作用，3）生活质量。虽然有充分的验证 疾病症状（＃1）和生活质量（＃3）的度量，没有验证的措施捕获 汽车T细胞疗法的独特副作用（＃2）。缺乏这样的措施限制试图进行研究和 病人对这种新疗法的教育。这项研究将开发并验证一个新的测量，以评估患者 - 报告了汽车T细胞疗法的副作用。衡量开发将遵循FDA测量开发 指南，提供英语和西班牙语。在AIM 1中，定性访谈将与20进行 汽车T细胞收件人，20位非正式家庭护理人员和20位具有CAR T细胞专业知识的医疗提供者 治疗。患者和护理人员将在整个表面轨迹上进行采样，以确保足够 自CAR T细胞疗法以来的各种经历的代表。定性访谈将确定患者 - 报告的副作用在整个汽车过程中都是常见，严重，令人痛苦且诊断重要的副作用 T细胞疗法，恢复和生存。副作用将映射到功能评估 慢性病疗法（FACIT）项目库，共700个独特的专业项目。新项目将用于副作用 没有相应的面孔项目。在AIM 2中，将对其他20名患者进行认知访谈 进行以确保项目库的可读性，可理解性和面部有效性以及生成 根据需要的其他项目。在AIM 3中，会聚，发散和判别有效性以及可靠性将是 自治疗以来，在一项评估150例CAR T细胞治疗患者的横断面研究中进行了评估。 当前的项目具有很高的创新性。从研究的角度来看，测量将提供重要的数据 与CAR T细胞治疗接受者进行的观察性，介入和治疗试验。来自临床 透视图，测量将导致更好地检测患者报告的副作用，以提高支持性 照顾这个人群。