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

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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.