P1 - COMBINATION ACTIVATED T-CELL AND VACCINE THERAPY IN MYELOMA

P1 - 骨髓瘤的激活 T 细胞和疫苗联合治疗

• 批准号: 7975980
• 负责人: LARRY W KWAK
• 金额: $ 98.02万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7975980
• 关键词: Active Immunization; Addendum; Adoptive Immunotherapy; Adoptive Transfer; Allogenic; Autologous; Autologous Stem Cell Transplantation; Autologous Transplantation; B-Lymphocytes; Bone Marrow; Cancer Center; Cell Transplants; Cells; Clinical; Clinical Protocols; Clinical Trials; Combination Drug Therapy; Combined Vaccines; Conduct Clinical Trials; Data; Disease; Disease-Free Survival; Dose; Enrollment; Feasibility Studies; Follicular Lymphoma; Generations; Goals; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; High Dose Chemotherapy; Human; Humoral Immunities; Immune; Immune response; Immunity; Immunoglobulin Idiotypes; Immunoglobulins; Immunologic Monitoring; Immunologics; Immunosuppression; Immunotherapy; Infusion procedures; Keyhole Limpet Hemocyanin; Laboratories; Learning; Lymphocyte; Lymphocyte Count; Lymphoma; Malignant - descriptor; Malignant Neoplasms; Measures; Mediating; Methods; Modeling; Multiple Myeloma; Natural Immunity; Newly Diagnosed; Outcome; Paraproteins; Patients; Pennsylvania; Phase; Phase II Clinical Trials; Plasma Cells; Pneumococcal vaccine; Positioning Attribute; Prognostic Factor; Protocols documentation; Randomized; Randomized Clinical Trials; Recovery; Regimen; Research Personnel; Resistance; Role; Safety; Saline; Series; Stem cell transplant; T-Lymphocyte; Testing; The Sun; Translating; Transplantation; Tumor Burden; Universities; University of Texas M D Anderson Cancer Center; Vaccinated; Vaccination; Vaccine Therapy; Vaccines; autologous lymphocytes; base; immunogenicity; immunosuppressed; improved; multiple myeloma M Protein; novel strategies; randomized trial; reconstitution; response; trend; tumor; tumor growth; vaccine candidate

Our team has made significant progress in our efforts to develop and validate methods to induce immunity in patients with hematologic malignancies. A central hypothesis of this application is that multiple biologic and immunologic maneuvers will be required in order to achieve long-term control of hematologic malignancies; similar to the finding that combination chemotherapy has been required to significantly improve sun/ival in most tumors. We have developed a candidate vaccine termed Id KLH, that targets the patient specific and tumor specific M-protein that is produced by myeloma cells. This vaccine, given as a single agent, has been demonstrated to have safety and clinical activity in phase II and phase 111 trials in follicular lymphoma. Complimenting the vaccine studies, our recent randomized phase l/ll studies in subjects with advanced myeloma showed adoptive immunotherapy with vaccine primed T cells resulted in an encouraging immunologic reconstitution following high dose chemotherapy and autologous hematopoietic stem cell transplantation (SCT). Furthermore, we provided the first evidence in humans that adoptive mmunotherapy combined with vaccinafion could result in the generation of protective immunity within weeks following the SCT. Based on these promising clinical results, and on the safety and feasibility of this clinical trial, we now propose a series of clinical trials to induce tumor-specific immunity in pafients with myeloma. To build on our combined progress, the following two specific aims will test the hypothesis that vaccines can be combined with adoptive immunotherapy in patients with myeloma with the goal of generating a moleculariy targeted and potent antitumor immunity: ¿ Specific Aim 1. Conduct a phase II clinical trial to study the feasibility and immunogenicity of post-transplant effector T cell reconstitution and Idiotype-KLH vaccination in patients with advanced myeloma. Obtain full regulatory clearance to open the protocol, and conduct the clinical trial. The protocol will be opened at the MD Anderson Cancer Center and the University of Pennsylvania, and closed to enrollment when -60 patients are enrolled. ¿ Specific Aim 2. Determine whether the combination immunotherapy regimen augments myeloma immunity and decreases tumor burdens. We will determine (a) cellular and (b) humoral immune responses and (c) learn whether this correlates with the degree of paraprotein reduction for all patients regardless of whether they received the vaccine or not and then amongst vaccine recipients alone. Based upon our preliminary data, we expect to see a trend between Id-specific immunity and a reduction of paraprotein levels.

我们的团队在努力开发和验证诱导方法方面取得了重大进展。 恶性血液病患者的免疫力。本申请的中心假设是， 需要生物和免疫策略，以实现血液学的长期控制。 恶性肿瘤;类似的发现，联合化疗已被要求显着 在大多数肿瘤中改善sun/ival。我们已经开发了一种名为Id KLH的候选疫苗， 由骨髓瘤细胞产生的患者特异性和肿瘤特异性M蛋白。这种疫苗，作为一种 单药，已在II期和111期试验中证明具有安全性和临床活性， 滤泡性淋巴瘤作为对疫苗研究的补充，我们最近在受试者中进行的随机I/II期研究 晚期骨髓瘤患者的研究表明，用疫苗引发的T细胞进行过继免疫治疗， 鼓励高剂量化疗和自体造血后的免疫重建 干细胞移植（SCT）。此外，我们提供了人类的第一个证据， 免疫治疗结合疫苗接种可在数周内产生保护性免疫 在SCT之后。基于这些有希望的临床结果，以及本临床试验的安全性和可行性， 试验，我们现在提出了一系列的临床试验，以诱导骨髓瘤患者的肿瘤特异性免疫。 为了巩固我们的综合进展，以下两个具体目标将检验疫苗可以 与骨髓瘤患者的过继免疫治疗相结合， 分子靶向和有效的抗肿瘤免疫： 具体目标1.开展II期临床试验，研究 移植后效应T细胞重建和特发性KLH疫苗接种在晚期乳腺癌患者中的作用 骨髓瘤获得全面的监管许可，以启动方案并进行临床试验。议定书 将在MD安德森癌症中心和宾夕法尼亚大学开放， 入组约60例患者。 具体目标2.确定联合免疫治疗方案是否增强骨髓瘤 免疫力和降低肿瘤负荷。我们将确定（a）细胞免疫和（B）体液免疫 反应和（c）了解这是否与所有患者的副蛋白减少程度相关 无论他们是否接种了疫苗，然后仅在疫苗接种者中。基于 根据我们的初步数据，我们预计会看到一种趋势，在ID特异性免疫和减少 副蛋白水平。