Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma

Stephen Maxted Ansell, Steven M. Horwitz, Andreas Engert, Khuda Dad Khan, Thomas Lin, Roger Strair, Tibor Keler, Robert Graziano, Diann Blanset, Michael Yellin, Steven Fischkoff, Albert Assad, Peter Borchmann

Research output: Contribution to journalArticle

207 Citations (Scopus)

Abstract

Purpose: MDX-060 is a human anti-CD30 immunoglobulin (Ig) G1κ monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed. Patients and Methods: In the phase I portion, MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of three to six patients. Twenty-one patients - 16 with Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and two with CD30+ T-cell lymphoma - were enrolled. Because of the lack of a defined MTD or dose-response correlation, the phase II portion was amended to include several dose levels. In the phase II portion, an additional 51 patients, 47 with HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg. Results: MDX-060 was well tolerated, and an MTD has not been identified. Only 7% of patients experienced grade 3 or 4 treatment-related adverse events. Among the 72 patients treated, clinical responses were observed in six. Twenty-five patients had stable disease, including five who remained free from progression 1 year after treatment. Conclusion: MDX-060 was well tolerated at doses up to 15 mg/kg. MDX-060 has limited activity as a single agent, but the minimal toxicity observed and the significant proportion of patients with stable disease suggests that further study of MDX-060 in combination with other therapies is warranted.

Original languageEnglish (US)
Pages (from-to)2764-2769
Number of pages6
JournalJournal of Clinical Oncology
Volume25
Issue number19
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

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Anaplastic Large-Cell Lymphoma
Hodgkin Disease
Maximum Tolerated Dose
iratumumab
T-Cell Lymphoma
Immunoglobulins
Lymphoma
Therapeutics
Monoclonal Antibodies
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma. / Ansell, Stephen Maxted; Horwitz, Steven M.; Engert, Andreas; Khan, Khuda Dad; Lin, Thomas; Strair, Roger; Keler, Tibor; Graziano, Robert; Blanset, Diann; Yellin, Michael; Fischkoff, Steven; Assad, Albert; Borchmann, Peter.

In: Journal of Clinical Oncology, Vol. 25, No. 19, 01.07.2007, p. 2764-2769.

Research output: Contribution to journalArticle

Ansell, SM, Horwitz, SM, Engert, A, Khan, KD, Lin, T, Strair, R, Keler, T, Graziano, R, Blanset, D, Yellin, M, Fischkoff, S, Assad, A & Borchmann, P 2007, 'Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma', Journal of Clinical Oncology, vol. 25, no. 19, pp. 2764-2769. https://doi.org/10.1200/JCO.2006.07.8972
Ansell, Stephen Maxted ; Horwitz, Steven M. ; Engert, Andreas ; Khan, Khuda Dad ; Lin, Thomas ; Strair, Roger ; Keler, Tibor ; Graziano, Robert ; Blanset, Diann ; Yellin, Michael ; Fischkoff, Steven ; Assad, Albert ; Borchmann, Peter. / Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 19. pp. 2764-2769.
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abstract = "Purpose: MDX-060 is a human anti-CD30 immunoglobulin (Ig) G1κ monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed. Patients and Methods: In the phase I portion, MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of three to six patients. Twenty-one patients - 16 with Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and two with CD30+ T-cell lymphoma - were enrolled. Because of the lack of a defined MTD or dose-response correlation, the phase II portion was amended to include several dose levels. In the phase II portion, an additional 51 patients, 47 with HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg. Results: MDX-060 was well tolerated, and an MTD has not been identified. Only 7{\%} of patients experienced grade 3 or 4 treatment-related adverse events. Among the 72 patients treated, clinical responses were observed in six. Twenty-five patients had stable disease, including five who remained free from progression 1 year after treatment. Conclusion: MDX-060 was well tolerated at doses up to 15 mg/kg. MDX-060 has limited activity as a single agent, but the minimal toxicity observed and the significant proportion of patients with stable disease suggests that further study of MDX-060 in combination with other therapies is warranted.",
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T1 - Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma

AU - Ansell, Stephen Maxted

AU - Horwitz, Steven M.

AU - Engert, Andreas

AU - Khan, Khuda Dad

AU - Lin, Thomas

AU - Strair, Roger

AU - Keler, Tibor

AU - Graziano, Robert

AU - Blanset, Diann

AU - Yellin, Michael

AU - Fischkoff, Steven

AU - Assad, Albert

AU - Borchmann, Peter

PY - 2007/7/1

Y1 - 2007/7/1

N2 - Purpose: MDX-060 is a human anti-CD30 immunoglobulin (Ig) G1κ monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed. Patients and Methods: In the phase I portion, MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of three to six patients. Twenty-one patients - 16 with Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and two with CD30+ T-cell lymphoma - were enrolled. Because of the lack of a defined MTD or dose-response correlation, the phase II portion was amended to include several dose levels. In the phase II portion, an additional 51 patients, 47 with HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg. Results: MDX-060 was well tolerated, and an MTD has not been identified. Only 7% of patients experienced grade 3 or 4 treatment-related adverse events. Among the 72 patients treated, clinical responses were observed in six. Twenty-five patients had stable disease, including five who remained free from progression 1 year after treatment. Conclusion: MDX-060 was well tolerated at doses up to 15 mg/kg. MDX-060 has limited activity as a single agent, but the minimal toxicity observed and the significant proportion of patients with stable disease suggests that further study of MDX-060 in combination with other therapies is warranted.

AB - Purpose: MDX-060 is a human anti-CD30 immunoglobulin (Ig) G1κ monoclonal antibody that inhibits growth of CD30-expressing tumor cells in preclinical models. To determine the safety, maximum-tolerated dose (MTD), and efficacy of MDX-060 in patients with relapsed or refractory CD30+ lymphomas, sequential phase I and II studies were performed. Patients and Methods: In the phase I portion, MDX-060 was administered intravenously at doses of 0.1, 1, 5, or 10 mg/kg weekly for 4 weeks to cohorts of three to six patients. Twenty-one patients - 16 with Hodgkin's lymphoma (HL), three with anaplastic large-cell lymphoma (ALCL), and two with CD30+ T-cell lymphoma - were enrolled. Because of the lack of a defined MTD or dose-response correlation, the phase II portion was amended to include several dose levels. In the phase II portion, an additional 51 patients, 47 with HL and four with ALCL, were treated at doses of 1, 5, 10, and 15 mg/kg. Results: MDX-060 was well tolerated, and an MTD has not been identified. Only 7% of patients experienced grade 3 or 4 treatment-related adverse events. Among the 72 patients treated, clinical responses were observed in six. Twenty-five patients had stable disease, including five who remained free from progression 1 year after treatment. Conclusion: MDX-060 was well tolerated at doses up to 15 mg/kg. MDX-060 has limited activity as a single agent, but the minimal toxicity observed and the significant proportion of patients with stable disease suggests that further study of MDX-060 in combination with other therapies is warranted.

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