A phase i study with an anti-cd30 ricin a-chain immunotoxin (ki-4.dga) in patients with refractory cd30+ Hodgkin's and non-Hodgkin's lymphoma

Roland Schnell, Oliver Staak, Peter Borchmann, Christine Schwartz, Bärbel Matthey, Hinrich Hansen, John Schindler, Victor Ghetie, Ellen S. Vitetta, Volker Diehl, Andreas Engert

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114 Scopus citations

Abstract

Ki-4.dgA is an anti-CD30 immunotoxin (IT) constructed by coupling the monoclonal antibody Ki-4 via a sterically hindered disulfide linker to deglycosylated ricin A-chain. This IT was efficacious in vitro and in SCID mice with disseminated human Hodgkin's lymphoma. Accordingly, a Phase I trial in patients (pts) with Hodgkin's lymphoma was designed. The objectives of this Phase I trial were to determine the maximum tolerated dose, the dose-limiting toxicities, pharmacokinetics, and antitumor activity. Seventeen pts with relapsed CD30+ lymphoma were treated with escalating doses (5, 7.5, or 10 mg/m2/cycle) of the IT as four bolus infusions on days 1, 3, 5, and 7 for one to three cycles. All of the pts had progressive disease and were heavily pretreated. Nine had primary progressive disease and 14 had advanced disease with massive tumor burdens. The mean age was 35 years (24-52 years). Peak serum concentrations of the intact IT varied from 0.23 to 1.1 μg/ml. Side effects and dose-limiting toxicities were related to vascular leak syndrome, i.e., decreases in serum albumin, edema, weight gain, hypotension, tachycardia, myalgia, and weakness. The maximum tolerated dose was 5 mg/m2. Seven of 17 (40%) pts made human antiricin antibodies (≥1.0 μg/ml), and 1 pt developed human antimouse antibodies (≥1.0 μg/ml). Clinical response in the 15 evaluable pts included 1 partial remission, 1 minor response, and 2 stable diseases. In conclusion, the IT was less well tolerated than other ITs of this type. This might be because of the low number of CD30+ peripheral blood mononuclear cells, and in part because of binding of the IT to soluble CD30 antigen and the resulting circulation of IT/sCD30 complexes.

Original languageEnglish (US)
Pages (from-to)1779-1786
Number of pages8
JournalClinical Cancer Research
Volume8
Issue number6
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Schnell, R., Staak, O., Borchmann, P., Schwartz, C., Matthey, B., Hansen, H., Schindler, J., Ghetie, V., Vitetta, E. S., Diehl, V., & Engert, A. (2002). A phase i study with an anti-cd30 ricin a-chain immunotoxin (ki-4.dga) in patients with refractory cd30+ Hodgkin's and non-Hodgkin's lymphoma. Clinical Cancer Research, 8(6), 1779-1786.