A.A Phase I Study of Continuous Infusion Immunotoxin IgG-HD37-SMPT-dgA in Refractory CD19-Positive B-Cell Lymphoma This trial examines the activity and pharmacologic features of the immunotoxin IgG-HD37-SMPT-dgA when given by continuous infusion. This agent consists of the monoclonal antibody HD37, directed at the B cell surface antigen CD19, linked to deglycosylated ricin A chain. The scientific question is whether the therapeutic index of this agent can be improved by this method of administration, in comparison to the bolus style of administration studied in other Phase Is. Ten patients have been entered, with two dose levels explored. Four patients have been studied at 9.6mg/M2/192 hr, and six patients have been treated at 19.2 mg/M2/192 hr. There have been OCR, OPR, 3MR, 4SD, 2PD, and 1NE. There have been three Grade III toxicities in the current level, thus defining the MTD. Pharmacologic analysis and comparison with our earlier antiCD22 trial are ongoing. It does not appear that continuous infusion allows markedly more dose to be administered than bolus programs. Nonetheless, the existence of clinical responses raises the question of whether combining with immunotoxins targeting other determinants will circumvent tumor cell heterogeneity, while targeting the same concentration range shown here to be safely administered. B. 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 our prior experience with the anti CD22-directed toxin IgG-RFB4-SMPT-dgA and the anti CD19-directed toxin IgG-HD37-SMPT- dgA. It has been approved recently by the Clinical Center, and is now just opening for accrual. The goal will be to define the MTD of the toxins administered as a """"""""cocktail"""""""", and compare this MTD to the prior studies which used them as single agents. In addition, the pharmacologic features of the individual toxins when administered together will be studied. This will be the first study in the world to use a combination of immunotoxins.
