Although radioimmunotherapy (RIT)appears to have promise as a new therapeutic modality for lymphoma, suboptimal delivery of radiation to tumor sites and dose-limiting myelosuppression remain as significant problems. The guiding hypothesis of this project is that RIT of B-cell lymphoma can be further enhanced a) through the use of radiolabeled monoclonal antibodies with more restricted specificity for Bcells than those previously used, b) through the manipulation of antibodydosing methods, and c) through the use of a bone marrow radioprotective cytokine such as interleukin-1-alpha (IL-1-alpha). To study theseinterrelated issues the applicant will perform a stepwise, three-part phaseI clinical trial. In Part I, the maximum tolerated dose (MTD) of 131-I-anti-B1 which does not require bone marrow transplantation support and is suitablefor a multiple dosing schedule will be determined by phase I radiation dose-escalation in successive groups of patients. As part of the assessment of toxicity, detailed studies regarding peripheral blood and bone marrow hematopoetic recovery (including bone marrow progenitor assays) will be performed. Also, in this part of the trial the issue of tumor targeting will be addressed in a study in which the effects of varying levels of unlabeled antibody predosing on the biodistribution of trace-labeled anti-B1 will be determined. The results from these tracer studies will be applied to the planningof the subsequent delivery of an RIT dose in each patient. In Part II, the feasibility, safety, and toxicity of combining IL-1-alpha with 131-I-anti-B1 will be determined in patients entered onto three successive escalating dose levels of IL-1-alpha given before the MTD of 131-I-anti-B1 determined in Part I. The same detailed hematologic studies will be performed in thesepatients who have received IL-1-alpha so that they may be compared to the patients not given IL-1-alpha in Part I. In part III, it will be determined whether a higher MTD of 131-I-anti-B1 can be given to patients who have received a pretreatment with IL-1-alpha. Detailed hematologic studies will continue to be performed for further comparative purposes.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA056794-02
Application #
3201205
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1992-06-01
Project End
1996-05-31
Budget Start
1993-06-01
Budget End
1994-05-31
Support Year
2
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Koral, K F; Li, J; Dewaraja, Y et al. (1999) I-131 anti-B1 therapy/tracer uptake ratio using a new procedure for fusion of tracer images to computed tomography images. Clin Cancer Res 5:3004s-3009s
Wahl, R L (1998) Iodine-131 anti-B1 antibody therapy in non-Hodgkin's lymphoma: dosimetry and clinical implications. J Nucl Med 39:1S
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