Determining Optimum Medical Therapy for ITP

确定 ITP 的最佳药物治疗

• 批准号: 8355524
• 负责人: JAMES BRUCE BUSSEL
• 金额: $ 41.79万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-15 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8355524
• 关键词: Adult; Aftercare; Belief; Blood Platelets; Bone Marrow; Case Report Form; Clinical Trials; Committee Members; Communication Methods; Communities; Consensus; Dexamethasone; Dose; Eligibility Determination; Enrollment; Excision; Goals; Grant; Hematologist; Hemorrhage; Hemostatic Agents; Immune; Immunotherapy; In complete remission; Institutional Review Boards; Lead; Long-Term Effects; MS4A1 gene; Manuals; Measures; Medical; Methods; Multicenter Studies; Operative Surgical Procedures; Outcome; Patients; Pharmaceutical Preparations; Pilot Projects; Placebos; Platelet Count measurement; Prednisone; Procedures; Process; Production; Protocols documentation; Questionnaires; Randomized; Recruitment Activity; Regulatory T-Lymphocyte; Resources; Safety; Sample Size; Science; Site; Spleen; Splenectomy; Steroids; Techniques; Thrombocytopenia; United States National Institutes of Health; abstracting; arm; base; comparative efficacy; comparative trial; design; falls; health related quality of life; improved; meetings; member; oncology; public health relevance; response; rituximab; trial comparing

DESCRIPTION (provided by applicant): Adults with Immune Thrombocytopenia (ITP) are usually treated initially with steroids. However, the great majority either do not improve or do no have a lasting response. The platelet count falls as the steroids are tapered or stopped and as a result, most patients require further therapy to maintain a hemostatic platelet count. However, there is no current consensus about the best option following steroids. The current choices consist of the medical options, more high dose steroids, rituximab (ritux), or thrombopoietic agents (TPO agents); or the surgical option, splenectomy. Prednisone leads to lasting effects in very few patients following a second course; high dose dexamethasone (dex), touted in single arm studies to have curative effects, had lasting effects in only 17% of patients in a recent comparative trial. Anti-CD20 (Rituximab, ritux) leads to initial benefit in 50% of ITP patients but3 years after treatment, it appears that only 20% of adults sustain satisfactory platelet counts. TPO agents stimulate bone marrow platelet production and multiple studies demonstrate efficacy as compared to standard /placebo. These agents clearly provide a useful therapy, but are expensive, have still unclear long-term effects, and it is believed that this treatment can never be withdrawn. As removal of the spleen is irreversible, has known medical consequences, and most patients do not wish to undergo splenectomy, we have explored combinations of medical options that may offer satisfactory alternatives. We have found that ritux in combination with dexamethasone (dex) resulted in complete remissions for one or more years in half of the patients treated in a recent pilot study. Contrary to belief, TPO agents appear to lead a sustained off treatment hemostatic platelet count in some cases, possibly via the induction of regulatory T cells (Tregs). Thus overall the goal of this proposed planning grant is to prepare for a clinical trial comparing the combination of dex with anti- CD20 to a TPO agent to see which arm leads to more patients with a lasting effect at 3 years from initial treatment. As pointed out at the NIH-sponsored State of the Science meeting in September 2009, a comparison of the best current medical therapies is urgently needed. We propose in this U34 grant to prepare for a multicenter study by having the Steering Committee form a consensus on the study protocol and interface with the U24 Resource group to gain statistical input, implement an IRB and IND, and design case report forms and other material such as a manual of procedures and to accrue the sites required to successfully complete the study.

描述（由申请人提供）：具有免疫血小板减少症（ITP）的成年人通常用类固醇治疗。但是，绝大多数人要么没有改善，要么没有持久的回应。血小板计数下降，因为类固醇是锥形或停止的，因此，大多数患者需要进一步的治疗才能维持止血的血小板计数。但是，关于类固醇的最佳选择尚无共识。当前的选择包括医疗选择，更多的高剂量类固醇，利妥昔单抗（Ritux）或血小板剂（TPO剂）；或手术选择，脾切除术。泼尼松会导致第二个病程后很少的患者产生持久的影响。高剂量地塞米松（DEX）在单臂研究中吹捧以具有治愈作用，在最近的一项比较试验中，仅在17％的患者中产生持久作用。抗CD20（利妥昔单抗，Ritux）可导致50％的ITP患者的初步受益，但治疗后3年，似乎只有20％的成年人维持令人满意的血小板计数。与标准 /安慰剂相比，TPO剂刺激骨髓血小板的产生，多项研究证明了功效。这些药物显然提供了一种有用的疗法，但价格昂贵，但仍然不清楚长期影响，并且人们认为这种疗法永远无法撤回。由于脾脏的去除是不可逆的，具有已知的医疗后果，并且大多数患者不希望进行脾切除术，因此我们探索了可能提供令人满意的替代方案的医疗选择组合。我们发现，与地塞米松（DEX）结合使用Ritux，在最近的一项试点研究中，在接受治疗的患者中，一半的患者中有一年或多年的完全缓解。与信念相反，在某些情况下，TPO药物似乎通过诱导调节性T细胞（Tregs）导致持续的止血性血小板计数。因此，总体而言，这项提议的计划赠款的目标是准备 一项将DEX与抗CD20与TPO剂组合的临床试验，以查看哪些ARM导致最初治疗后3年有持久作用的患者更多。正如2009年9月在NIH赞助的科学会议上指出的那样，迫切需要对当前最佳医疗疗法进行比较。我们在本U34赠款中建议通过指导委员会在研究方案上达成共识，并与U24资源组达成共识，并与U24 Resource Group达成共识，以获得统计输入，实施IRB和IND，以及设计案例报告表格和其他材料，例如手动的程序并累积了该研究所需的站点以连续完成该研究。