Vitamin D and Follicular Lymphoma

维生素 D 和滤泡性淋巴瘤

• 批准号: 9502928
• 负责人: JONATHAN W FRIEDBERG
• 金额: $ 61.51万
• 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/9502928
• 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; Immuno-Chemotherapy; 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; 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; immunomodulatory drugs; improved; improved outcome; insight; macrophage; novel; patient subsets; predicting response; primary endpoint; prognostic; prospective; randomized placebo controlled trial; randomized trial; response; rituximab; secondary endpoint; 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.

抽象的 惰性非霍奇金淋巴瘤是不治之症，需要间歇性且经常治疗 在其漫长的自然史中进行病态且昂贵的治疗。较低的强度和 这些患者需要耐受性更好、具有成本效益的治疗策略。维生素含量低 惰性淋巴瘤诊断时的 D 水平与较差的预后密切相关 治疗。低肿瘤负荷惰性淋巴瘤的标准疗法包括单一药物 单克隆抗体（利妥昔单抗）。在这项提案中，我们将完成一项双盲、安慰剂- 评估是否每天补充 2000IU 口服片剂维生素 D 的对照随机试验 三年改善惰性淋巴瘤患者的无进展生存期 用单药利妥昔单抗治疗。随机化的分层因素将包括组织学 和 FL-IPI 预后评分。该试验的主要终点是无进展生存期 三年；次要终点包括 13 周时的反应和总生存期。计划 子集分析包括滤泡性淋巴瘤组织学和女性。 210 随机 对于患者，我们将有 80% 的功效在两侧 alpha = 0.05 水平上检测到 HR = 0.55 意义。该临床试验将在罗切斯特大学威尔莫特癌症中心协调 研究所和淋巴瘤流行病学结果的六个专家淋巴瘤中心 （LEO）财团将参与。我们将利用这个 LEO 联盟进行肿瘤库和 入组患者的前瞻性患者报告结果。我们还将确定基线是否 和/或重新分期血清维生素 D 水平可预测服用维生素 D 的患者亚组 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) 的特定基因型，我们将 利用全外显子组测序来确定与维生素 D 相关的种系变异是否 补充维生素 D 的患者结果的关键决定因素 惰性淋巴瘤。我们的目标是确定补充维生素 D 的阈值水平 是最有效的，种系多态性对结果的影响将为未来的试验提供信息 设计并有助于机械理解。证明维生素 D 的益处 这项随机试验中的补充剂将迅速改变大多数国家的护理标准 惰性淋巴瘤的常见表现，并提供低风险、耐受性良好、廉价的治疗方案 选择延迟病态治疗的时间。