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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 滤泡型和滤泡型转化的NHL患者骨髓侵犯恶性B细胞的发生率较高。此外，淋巴瘤骨髓活检阴性的患者仍有相当数量的正常骨髓B细胞。因此，注射针对B细胞抗原的放射性标记单抗会导致放射性标记抗体在骨髓中的特异性定位，从而产生超过干细胞辐射的干细胞辐射效应，这是由于标准剂量学技术估计的循环放射性标记抗体所致。我们的假设是，90Y-Zvalin治疗策略允许逆转恶性B细胞的骨髓渗透，应该允许90Y-Zvalin剂量的大幅增加，这可以被患者很好地耐受，从而增加对淋巴瘤肿瘤部位的辐射。由于非霍奇金淋巴瘤对辐射敏感，辐射剂量的大幅增加应该会增加ORR和CR率。因此，一个完整疗程的Rituxan每周375 mg/m2，共4次，用于清除骨髓中恶性和正常B细胞，然后标准90Y-Zvalin方案，250 mg/m2 Rituxan+5 mCI 111In-Zvalin用于剂量测定，1周后给予250 mg/m2 Rituxan+90Y-Zvalin剂量递增队列。这一治疗策略的目的是开发一种基于单抗的治疗方案，最大限度地诱导12周治疗方案的完全缓解。 本研究的目的是：(1)建立每周服用4剂Rituxan后无NHL骨髓浸润的患者的90Y-Zvalin的MTD；(2)建立每周4剂Rituxan后不同剂量90Y-Zvalin的毒性；(3)建立不同剂量水平的111In-Zvalin对肿瘤部位、全身和正常器官的剂量学；(4)确定4剂Rituxan后NHL骨髓受累逆转的频率；(5)虽然不是一个主要或明确的目标，但描述在不同剂量水平的90Y-Zvalin治疗的患者中抗肿瘤反应的程度。

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.