A. A Pilot Phase I Study of Combination Therapy with Continuous Infusion Immunotoxins IgG-RFB4-SMPT-dgA plus IgG-HD37-SMPT-dgA in Refractory CD19+, CD22+ B cell Lymphoma. This study builds on the prior experience with the respective immunotoxins utilized as single agents and seeks to determine the safety of the cocktail administered together as well as seeking to obtain some initial evidence of efficacy. Two dose levels(5 and 10 mg/M2/192 hr of each toxin have been thus far studied. There is initial evidence that the MTD will differ depending on whether circulating tumor cells are in evidence. Two of three patients without circulating tumor cells experienced Grade III toxicity at the higher dose level, whereas none of three patients with circulating tumor cells experienced Grade III toxicity or greater. Initial evidence has been obtained that in the same patient the handling of the immunotoxins differed depending on the expression of the target antigens. B. Correlative studies with Immunotoxins and Unconjugated Antibodies. In correlative laboratory studies to determine the relation of growth inhibition in tumor cell lines to the expression of the target antigens and clinical pharmacology of the agents, we observed that HD37 antibody was as effective in some respects as an antiproliferative agent as the IgG-HD37-SMPT-dgA immunotoxin. The antibody caused G1 arrest and hypophosphorylation of pRb. These results suggest that the negative growth regulatory effects of an antibody may complement the cytotoxic action of an immunotoxin in combined approaches.
