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）：患有免疫性血小板减少症（ITP）的成人通常最初用类固醇治疗。然而，绝大多数人要么没有改善，要么没有持久的反应。随着类固醇逐渐减少或停止，血小板计数下降，因此，大多数患者需要进一步治疗以维持止血血小板计数。然而，目前对于类固醇治疗后的最佳选择尚未达成共识。目前的选择包括医疗选择、更高剂量的类固醇、利妥昔单抗（ritux）或血小板生成剂（TPO 剂）；或手术选择，脾切除术。泼尼松在极少数患者中在第二个疗程后会产生持久效果；高剂量地塞米松 (dex) 在单臂研究中被吹捧为具有疗效，但在最近的一项比较试验中，仅对 17% 的患者产生持久效果。抗 CD20（利妥昔单抗，ritux）最初使 50% 的 ITP 患者受益，但治疗 3 年后，似乎只有 20% 的成年人维持令人满意的血小板计数。 TPO 药物可刺激骨髓血小板生成，多项研究证明与标准/安慰剂相比具有功效。这些药物显然提供了一种有用的治疗方法，但价格昂贵，长期效果仍不清楚，并且人们相信这种治疗永远不会被撤销。由于脾脏切除是不可逆转的，具有已知的医疗后果，并且大多数患者不希望接受脾切除术，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，在最近的一项试点研究中，利妥昔单抗与地塞米松 (dex) 联合使用可使一半的患者完全缓解一年或多年。与人们的看法相反，在某些情况下，TPO 药物似乎可以通过诱导调节性 T 细胞 (Treg) 来持续维持治疗后的止血血小板计数。因此，总体而言，拟议规划拨款的目标是为 一项临床试验，将 dex 与抗 CD20 的组合与 TPO 药物进行比较，以了解哪一种药物可以使更多患者在初次治疗后 3 年内获得持久效果。正如 2009 年 9 月 NIH 主办的科学状况会议所指出的那样，迫切需要对当前最好的医学疗法进行比较。我们建议在这项 U34 拨款中，让指导委员会就研究方案达成共识，并与 U24 资源组联系，以获取统计输入、实施 IRB 和 IND，并设计病例报告表和其他材料，为多中心研究做准备。例如程序手册并积累成功完成研究所需的地点。