Vitamin D and Follicular Lymphoma

维生素 D 和滤泡性淋巴瘤

• 批准号: 9397911
• 负责人: JONATHAN W FRIEDBERG
• 金额: $ 70.22万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9397911
• 关键词: Affect; Aftercare; Age; Apoptosis; Binding; Blood; Cell Line; Cell Proliferation; Cell-Mediated Cytolysis; Cholecalciferol; Chronic; Clinical Research; Clinical Trials; Comorbidity; Data; Diagnosis; Disease; Dose; Double-Blind Method; Enrollment; Epidemiology; Europe; Female; Financial cost; Follicular Lymphoma; Food; Future; Genetic Polymorphism; Genetic Transcription; Genotype; Histology; Human; Impairment; In Vitro; Indolent; Inferior; Institutes; Lymphatic Diseases; Lymphoma; Malignant Neoplasms; Mediating; Monoclonal Antibodies; Morbidity - disease rate; Natural History; Non-Hodgkin' s Lymphoma; Nuclear; Oral; Outcome; Pathway interactions; Patient Outcomes Assessments; Patients; Pharmaceutical Preparations; Placebos; Population; Prognostic Factor; Progression-Free Survivals; Quality of life; Randomized; Randomized Clinical Trials; Reporting; Risk; Safety; Serum; Side; Skin; Source; Stem cell transplant; Stratification Factors; Subgroup; Sun Exposure; System; Tablets; Therapeutic; Time; Treatment outcome; Tumor Burden; United States; Universities; Variant; Vitamin D; Vitamin D Deficiency; Vitamin D supplementation; Vitamin D-Binding Protein; Vitamin D3 Receptor; aggressive therapy; burden of illness; cell type; chemotherapy; cholecalciferol supplementation; cost; cost effective; dietary supplements; exome sequencing; immunoregulation; improved; improved outcome; insight; macrophage; novel; patient subsets; predicting response; prognostic; prospective; randomized placebo controlled trial; randomized trial; response; rituximab; sex; standard care; standard of care; targeted agent; treatment strategy; trial design; tumor; virtual

ABSTRACT Indolent non-Hodgkin lymphomas are incurable diseases, and require intermittent and often morbid and expensive therapy during their prolonged natural history. Lower intensity and better-tolerated, cost-effective treatment strategies are needed for these patients. Low vitamin D levels at diagnosis of indolent lymphomas are strongly associated with inferior outcomes to treatment. Standard therapy for low tumor burden, indolent lymphoma includes a single agent monoclonal antibody (rituximab). In this proposal, we will complete a double-blind, placebo- controlled randomized trial evaluating if vitamin D supplementation with 2000IU oral tablets daily for three years improves the progression-free survival of patients with indolent lymphoma treated with single agent rituximab. Stratification factors for randomization will include histology and FL-IPI prognostic score. The primary endpoint of the trial is progression-free survival over three years; secondary endpoints include response at 13 weeks, and overall survival. Planned subset analyses include follicular lymphoma histology and female sex. With 210 randomized patients, we will have 80% power to detect a HR = 0.55 at a two sided alpha = 0.05 level of significance. This clinical trial will be coordinated at the University of Rochester Wilmot Cancer Institute, and six expert lymphoma centers from the Lymphoma Epidemiology of Outcomes (LEO) Consortium will participate. We will leverage this LEO consortium for tumor banking and prospective patient-reported outcomes of enrolled patients. We will also identify if baseline and/or restaging serum vitamin D levels predict subgroups of patients for whom Vitamin D supplementation is particularly effective or particularly ineffective. Finally, since there is evidence to suggest that response to oral vitamin D supplementation may be dependent upon specific genotypes of the Vitamin D receptor (VDR) and vitamin D binding protein (DPB), we will utilize whole exome sequencing to determine whether vitamin D-related germline variations are critical determinants of outcome in the context of vitamin D supplementation of patients with indolent lymphoma. Our aims the defining threshold levels of vitamin D where supplementation is most effective and the impact of germline polymorphisms on outcome will inform future trial designs and contribute to mechanistic understanding. Demonstrating a benefit to vitamin D supplementation in this randomized trial would rapidly change standard of care in the most common presentation of indolent lymphoma, and provide a low-risk, well-tolerated, inexpensive option delaying the time to morbid treatments.

摘要 惰性非霍奇金淋巴瘤是不治之症，需要间歇性的和经常的 在他们漫长的自然历史中进行病态和昂贵的治疗。较低的强度和 对于这些患者，需要更好的耐受性和成本效益的治疗策略。低维生素 惰性淋巴瘤诊断时的D水平与预后不良密切相关 治疗。低肿瘤负担、惰性淋巴瘤的标准治疗包括单一药物 单抗(美罗华)。在这项提案中，我们将完成双盲、安慰剂- 每日口服2000IU片剂是否补充维生素D的随机对照试验 三年可提高惰性淋巴瘤患者的无进展生存率 用单剂利妥昔单抗治疗。随机化的分层因素将包括组织学 FL-IPI预后评分。试验的主要终点是无进展生存。 三年；次要终点包括13周的反应和总存活率。计划中的 亚组分析包括滤泡性淋巴瘤组织学和女性性别。随机化210人 患者，我们将有80%的能力在双侧α=0.05水平下检测HR=0.55 意义。这项临床试验将在罗切斯特·威尔莫特癌症大学进行协调 和来自淋巴瘤流行病学的六个淋巴瘤专家中心的结果 (LEO)财团将参与。我们将利用这个Leo财团进行肿瘤银行业务和 预期患者-登记患者的报告结果。我们还将确定基线是否 和/或恢复血清维生素D水平可预测维生素D 补充特别有效或特别无效。最后，既然有 有证据表明，口服维生素D补充剂的反应可能取决于 维生素D受体(VDR)和维生素D结合蛋白(DPB)的特定基因类型，我们将 利用整个外显子组测序来确定维生素D相关的生殖系变异是否 维他命D补充剂对慢性阻塞性肺疾病患者预后的关键决定因素 惰性淋巴瘤。我们的目标是定义维生素D的阈值水平，即补充 是最有效的，生殖系多态对结果的影响将为未来的试验提供信息 设计并有助于机械性理解。展示维生素D的益处 这项随机试验中的补充剂将在最大程度上迅速改变护理标准 常见的惰性淋巴瘤的表现，并提供一种低风险、耐受性好、价格低廉的 选择推迟病态治疗的时间。