CD38-TARGETED IMMUNOPET OF MYELOMA: PHASE 2 TRIAL OF CLINICAL APPLICATIONS

CD38 靶向骨髓瘤免疫宠物：临床应用 2 期试验

基本信息

批准号：
10684341
负责人：
Carl Ola Landgren
金额：
$ 4万
依托单位：
HOAG MEMORIAL HOSPITAL PRESBYTERIAN
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10684341
关键词：
Antibodies Biopsy Blood Tests Bone marrow biopsy Cells Clinical Clinical Trials Combined Modality Therapy Detection Detection of Minimal Residual Disease Disease Funding Opportunities Future Goals Histologic Human Image ImmunoPET Immunoglobulins Investigation Laboratories Measurement Measures Membrane Proteins Memorial Sloan-Kettering Cancer Center Methods Monitor Monoclonal Antibodies Multiple Myeloma PET/CT scan Patient Care Patient Monitoring Patient imaging Patients Phase Phase I Clinical Trials Phase II Clinical Trials Plasma Cell Neoplasm Plasma Cells Positron-Emission Tomography Prognosis Prognostic Marker Proteins Radiochemistry Radioimmunotherapy Radiolabeled Research Personnel Residual Tumors Safety Selection for Treatments Serum Site Surface Therapeutic Agents Tracer Translations Tumor Burden United States Visualization Work base blind burden of illness cancer imaging clinical application clinical care clinically significant design dosimetry early phase trial experience first-in-human fluorodeoxyglucose positron emission tomography human imaging imaging agent imaging modality individual patient innovation multiple myeloma M Protein novel phase I trial phase II trial preclinical imaging predicting response targeted imaging theranostics treatment response tumor uptake virtual

Antibodies Biopsy Blood Tests Bone marrow biopsy Cells Clinical Clinical Trials Combined Modality Therapy Detection Detection of Minimal Residual Disease Disease Funding Opportunities Future Goals Histologic Human Image ImmunoPET Immunoglobulins Investigation Laboratories Measurement Measures Membrane Proteins Memorial Sloan-Kettering Cancer Center Methods Monitor Monoclonal Antibodies Multiple Myeloma PET/CT scan Patient Care Patient Monitoring Patient imaging Patients Phase Phase I Clinical Trials Phase II Clinical Trials Plasma Cell Neoplasm Plasma Cells Positron-Emission Tomography Prognosis Prognostic Marker Proteins Radiochemistry Radioimmunotherapy Radiolabeled Research Personnel Residual Tumors Safety Selection for Treatments Serum Site Surface Therapeutic Agents Tracer Translations Tumor Burden United States Visualization Work base blind burden of illness cancer imaging clinical application clinical care clinically significant design dosimetry early phase trial experience first-in-human fluorodeoxyglucose positron emission tomography human imaging imaging agent imaging modality individual patient innovation multiple myeloma M Protein novel phase I trial phase II trial preclinical imaging predicting response targeted imaging theranostics treatment response tumor uptake virtual

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项目摘要

Project Summary / Abstract Multiple myeloma is a plasma cell neoplasm with poor prognosis but promising future treatment. Current measurements of myeloma disease burden are suboptimal, and this limits clinical care. We have completed a first-in-human trial of CD38-targeted immunoPET with the radiolabeled anti-CD38 monoclonal antibody, 89Zr- DFO-daratumumab, which very successfully visualized myeloma disease burden as never done before. This proposal is a phase 2 clinical trial to identify clinically valuable applications of CD38-targeted immunoPET in patients with multiple myeloma. Our central hypothesis is that targeted imaging of CD38, which is expressed on the surface of virtually every myeloma cell, will allow clinically valuable non-invasive immuno-PET imaging of patients with myeloma. This would be a transformative strategy for the measurement of myeloma tumor burden, selection of therapeutic agents, and monitoring of treatment response. In the first aim of the study, we will determine the correlation between tumor uptake of 89Zr-DFO-daratumumab with clinically standard laboratory and imaging measurement of myeloma, including patient serum M protein concentration, percentage of plasma cells on bone marrow biopsy, FDG PET/CT, and whole-body MR. Because current approaches to assessing myeloma tumor burden are sub-optimal, developing a method to sensitively visualize and localize myeloma could have a profound impact on patient care. In the second aim of the study, we will determine if tumor uptake of 89Zr-DFO-daratumumab predicts response to daratumumab-containing combination therapy. Not all patients respond to daratumumab therapy; thus, a method of predicting response would be valuable for selection of therapy in individual patients. In the third aim, we will determine if 89Zr-DFO-daratumumab imaging following daratumumab-containing combination therapy can detect clinically significant residual disease. Detection of minimal residual disease (MRD) following therapy continues to grow in importance as a prognostic marker and endpoint in myeloma clinical trials. A method of visualizing and localizing residual disease would impact patient care, as well as enhance trials of developing myeloma therapies. The ultimate goal of this work would be the identification of clinically valuable applications for 89Zr-DFO- daratumumab immunoPET and, if successful, advancement toward FDA approval of this agent.

项目摘要 /摘要多发性骨髓瘤是一种浆细胞肿瘤，预后不良，但有希望的未来治疗。当前的骨髓瘤疾病负担的测量值次优，这限制了临床护理。我们已经完成了 CD38靶向免疫集的首次人类试验与放射性标记的抗CD38单克隆抗体，89ZR-- DFO-DARATUMUMUMAB非常成功地可视化骨髓瘤负担，就像以前从未做过的那样。这提案是一项第二阶段临床试验，旨在识别CD38靶向免疫集的临床有价值的应用多发性骨髓瘤的患者。我们的中心假设是CD38的靶向成像，该成像几乎在每个表面上表达骨髓瘤细胞将允许骨髓瘤患者的临床上有价值的非侵入性免疫PET成像。这将是测量骨髓瘤肿瘤负担的变革性策略，选择治疗代理和治疗反应的监测。在研究的第一个目的中，我们将确定肿瘤吸收89zr-dfo-daratumumab之间的相关性具有临床标准的实验室和骨髓瘤的成像测量，包括患者血清M蛋白浓度，骨髓活检，FDG PET/CT和全身MR上的浆细胞百分比。因为当前评估骨髓瘤肿瘤负担的方法是次优的，开发了一种敏感的方法可视化和局部骨髓瘤可能会对患者护理产生深远的影响。在研究的第二个目的中，我们将确定肿瘤吸收89ZR-DFO-DARATUMUMAB是否可以预测反应到含daratumab的组合疗法。并非所有患者都对达拉特珠单抗治疗做出反应；因此，预测反应的方法对于选择个别患者的治疗很有价值。在第三个目标中，我们将确定含Daratumumab的89ZR-DFO-DARATUMUMUMAB成像是联合疗法可以检测到临床上重要的残留疾病。发现最小残留疾病（MRD）在治疗后，作为预后标记和骨髓瘤终点的重要性继续增长临床试验。一种可视化和定位残留疾病的方法会影响患者护理，以及增强开发骨髓瘤疗法的试验。这项工作的最终目标是确定89ZR-DFO-临床上有价值的应用 daratumumab免疫集，如果成功，则促进FDA批准该代理。