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A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT- dgA)
in patients with refractory Hodgkin's lymphoma
A Engert, V Diehl, R Schnell, A Radszuhn, MT Hatwig, S Drillich, G Schon, H Bohlen, H Tesch, ML Hansmann, S Barth, J Schindler, V Ghetie, J Uhr and E Vitetta
Klinik I fuer Innere Medizin, Universitaet zu Koeln, Germany.
The anti-CD25 immunotoxin (IT), RFT5-SMPT-dgA, was used in a phase I dose
escalation trial in patients with refractory Hodgkin's lymphoma. The IT was
constructed by linking the monoclonal antibody RFT5 via a sterically
hindered disulfide linker to deglycosylated ricin-A. All patients in this
trial were heavily pretreated with a mean of 5 (range, 2 to 8) different
prior therapies, including autologous bone marrow transplantation in 8 of
15. The mean age was 29 years (range, 19 to 34 years). Thirteen of 15
patients had advanced disease (stage IV) with massive 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/m2.
Patients received one to four cycles of treatment. The peak serum
concentration of intact IT varied from 0.2 to 9.7 micrograms/mL. The serum
half life (T1/2) of the IT ranged from 4.0 to 10.5 hours (mean, 6.1 hours).
Side effects were related to vascular leak syndrome (VLS), ie, decreases in
serum albumin, edema, weight gain, hypotension, tachycardia, myalgia, and
weakness. Two patients had a National Cancer Institute (NCI) grade 2
allergic reaction with generalized urticaria and mild bronchospasm. At 15
mg/m2, 1 patient experienced a grade 3 myalgia. All 3 patients receiving 20
mg/m2 experienced NCI grade 3 toxicities (edema, nausea, dyspnea or
tachycardia) and 1 patient had NCI grade 4 myalgia. Thus, the maximal
tolerated dose was 15 mg/m2. Seven of 15 patients made human antiricin
antibodies (> or = 1.0 microgram/mL) and 6 of 15 developed human
antimouse antibodies (> or = 1.0 microgram/mL). Clinical response
included 2 partial remissions, 1 minor response, 3 stable diseases, and 9
progressive diseases. As has been predicted from the preclinical tests,
these data seem to indicate clinical efficacy of this new IT in heavily
pretreated Hodgkin's patients, thus warranting further clinical
investigation.
Volume 89,
Issue 2,
pp. 403-410,
01/15/1997
Copyright © 1997 by The American Society of Hematology
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