90Y-ZEVALIN RADIOIMMUNOTHERAPY USING A MODIFIED TREATMENT REGIMEN FOR RELAPSED O

使用改良治疗方案的 90Y-Zevalin 放射免疫疗法治疗复发性 O

• 批准号: 7603176
• 负责人: RUBY F. MEREDITH
• 金额: $ 0.14万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603176
• 关键词: Antigens; Antitumor Response; B-Lymphocytes; Bone Marrow; Bone Marrow Involvement; Bone marrow biopsy; Computer Retrieval of Information on Scientific Projects Database; Disease remission; Dose; Frequencies; Funding; Grant; Incidence; Infiltration; Institution; Lymphoma; Malignant - descriptor; Marrow; Monoclonal Antibodies; Organ; Patients; Personal Satisfaction; Population; Radiation; Radioimmunoconjugate; Radioimmunotherapy; Radiolabeled; Rate; Relapse; Research; Research Personnel; Resources; Roche brand of rituximab; Site; Source; Standards of Weights and Measures; Stem cells; Toxic effect; Treatment Protocols; United States National Institutes of Health; Week; Y 90 Ibritumomab Tiuxetan; base; cohort; dosage; dosimetry; radiation effect; radiotracer; tumor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Patients with follicular and follicular transformed NHL have a high incidence of marrow involvement with malignant B-cells. In addition, patients with negative bone marrow biopsies for lymphoma still have a significant population of normal marrow B-cells. Thus, administration of radiolabeled monoclonal antibodies directed to B-cell antigens result in specific localization of radiolabeled antibodies in the bone marrow with resultant stem cell radiation effects above and beyond the stem cell radiation due to circulating radiolabeled antibodies as estimated by standard dosimetry techinques. Our hypothesis is that a 90Y-Zevalin treatment strategy which allows reversal of marrow infiltration with malignant B-cells should allow a substantial increase in the dosage of 90Y-Zevalin which could be well tolerated by patients with resultant increment in radiation delivered to lymphoma tumor sites. Since NHL is radiation sensitive, a substantial increase in radiation dose delivered should increase the ORR and CR rates. Thus, a full course of Rituxan at 375 mg/m2 weekly for 4 doses will be utilized to clear the marrow of malignant and normal B-cells and then the standard 90Y-Zevalin regimen of 250 mg/m2 of Rituxan plus 5 mCi of 111In-Zevalin for dosimetry will be administered followed 1 week later by 250 mg/m2 of Rituxan plus 90Y-Zevalin in increasing dose cohorts. The intent of this treatment strategy is to develop a monoclonal-based treatment regimen, which maximizes the induction of complete remission from a 12-week treatment regimen. The objectives of the study are to: (1) establish the MTD of 90Y-Zevalin administered to patients who do not have NHL marrow infiltration following 4 weekly doses of Rituxan; (2) establish the toxicity of different doses of 90Y-Zevalin administered at different doses following 4 weekly doses of Rituxan; (3) establish the dosimetry of 111In-Zevalin for tumor sites whole body and normal organs at these varying dose levels; (4) determine the frequency of reversal of bone marrow involvement with NHL after 4 doses of Rituxan; (5) while not a primary or definitive objective, describe the extent of antitumor response in patients treated at varying dose levels of 90Y-Zevalin.

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