A phase-I study of an anti-CD25 ricin A-chain immunotoxin (RFT5-SMPT- dgA) in patients with refractory Hodgkin's lymphoma

Andreas Engert, Volker Diehl, Roland Schnell, Andrea Radszuhn, Maria Theresia Hatwig, Silke Drillich, Gisela Schön, Heribert Bohlen, Hans Tesch, Martin Leo Hansmann, Stefan Barth, John Schindler, Victor Ghetie, Jonathan Uhr, Ellen Vitetta

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129 Scopus citations

Abstract

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 μg/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 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 (≤1.0 μg/mL) and 6 of 15 developed human antimouse antibodies (≤1.0 μg/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 effecicacy of this new IT in heavily pretreated Hodgkin's patients, thus warranting further clinical investigation.

Original languageEnglish (US)
Pages (from-to)403-410
Number of pages8
JournalBlood
Volume89
Issue number2
DOIs
StatePublished - Jan 15 1997

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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