A PHASE-I STUDY OF AN ANTI-CD25 RICIN A-CHAIN IMMUNOTOXIN (RFT5-SMPT-DGA) IN PATIENTS WITH REFRACTORY HODGKINS LYMPHOMA

The anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, was used in a phase I d ose escalation trial in patients with refractory Hodgkin's lymphoma. T he IT was constructed by linking the monoclonal antibody RFT5 via a st erically hindered disulfide linker to deglycosylated ricin-A. All pati ents in this trial were heavily pretreated with a mean of 5 (range, 2 to 8) different prior therapies, including autologous bone marrow tran splantation in 8 of 15. The mean age was 29 years (range, 19 to 34 yea rs). Thirteen of 15 patients had advanced disease (stage IV) with mass ive tumor burdens and 6 of 15 had B symptoms. The IT was administered intravenously over 4 hours on days 1, 3, 5, and 7 for total doses per cycle of 5, 10, 15, or 20 mg/m(2). Patients received one to four cycle s of treatment. The peak serum concentration of intact IT varied from 0.2 to 9.7 mu g/mL. The serum half life (T-1/2) of the IT ranged from 4.0 to 10.5 hours (mean, 6.1 hours). Side effects were related to vasc ular leak syndrome (VLS), ie, decreases in serum albumin, edema, weigh t gain, hypotension, tachycardia, myalgia, and weakness. Two patients had a National Cancer Institute (NCI) grade 2 allergic reaction with g eneralized urticaria and mild bronchospasm. At 15 mg/m(2), 1 patient e xperienced a grade 3 myalgia. All 3 patients receiving 20 mg/m(2) expe rienced NCI grade 3 toxicities (edema, nausea, dyspnea or tachycardia) and 1 patient had NCI grade 4 myalgia. Thus, the maximal tolerated do se was 15 mg/m(2). Seven of 15 patients made human antiricin antibodie s (greater than or equal to 1.0 mu g/mL) and 6 of 15 developed human a ntimouse antibodies (greater than or equal to 1.0 mu g/mL). Clinical r esponse included 2 partial remissions, 1 minor response, 3 stable dise ases, and 9 progressive diseases. As has been predicted from the precl inical tests, these data seem to indicate clinical effecicacy of this new IT in heavily pretreated Hodgkin's patients, thus warranting furth er clinical investigation. (C) 1997 by The American Society of Hematol ogy.