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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 滤泡性和滤泡性转化NHL患者骨髓恶性B细胞浸润的发生率很高。此外，淋巴瘤骨髓活检阴性的患者仍有大量正常的骨髓B细胞。因此，针对B细胞抗原的放射性标记单克隆抗体的给药导致放射性标记抗体在骨髓中的特异性定位，所产生的干细胞辐射效应高于和超过由标准剂量测定技术估计的循环放射性标记抗体引起的干细胞辐射。我们的假设是，允许逆转恶性B细胞骨髓浸润的90 Y-泽娃灵治疗策略应该允许90 Y-泽娃灵剂量的大幅增加，这可以被患者很好地耐受，从而增加递送到淋巴瘤肿瘤部位的辐射。由于NHL对放射敏感，因此放射剂量的大幅增加应会增加ORR和CR率。因此，将采用每周375 mg/m2的Rituxan全疗程，共4次给药，以清除骨髓中的恶性和正常B细胞，然后将给予250 mg/m2 Rituxan加5 mCi 111 In-Zevalin的标准90 Y-Zevalin方案用于剂量测定，1周后在剂量递增队列中给予250 mg/m2 Rituxan加90 Y-Zevalin。该治疗策略的目的是开发一种基于单克隆的治疗方案，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）确定在4周一次的Rituxan给药后，对没有NHL骨髓浸润的患者给予90 Y-泽娃灵的MTD;（2）确定在4周一次的Rituxan给药后，以不同剂量给予不同剂量的90 Y-泽娃灵的毒性;（3）建立111 In-Zevalin在这些不同剂量水平下对肿瘤部位、全身和正常器官的剂量测定法：（4）测定4个剂量Rituxan后NHL骨髓受累逆转的频率;（5）虽然不是主要或确定性目的，但描述在不同剂量水平的90 Y-泽娃灵治疗的患者中的抗肿瘤反应程度。

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.