Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for Interkeukin-2

Authors

Charles LeMaistre, University of Alabama, Birmingham, USA
Mansoor Saleh, Aga Khan UniversityFollow
Timothy Kuzel, University of Alabama,USA
Francine Foss, University of Alabama, USA
Leonidas Platanias, University of Alabama, USA
Gary Schwartz, University of Alabama, USA
Mark Ratain, University of Alabama, USA
Alain Rook, University of Alabama, USA

Document Type

Article

Department

Haematology and Oncology, East Africa

Abstract

The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and possible antitumor activity of a ligand fusion-protein, DAB₃₈₉IL-2, in a phase I trial. This was a multicenter, open-label, dose-escalation trial. Patients with preserved organ function and histologically confirmed relapsed cutaneous T-cell lymphoma (CTCL), other non-Hodgkin's lymphomas (NHL), or Hodgkin's disease (HD) were eligible if their cancer was shown to express the interleukin (IL)-2 receptor by an immunohistochemical assay for the p55 or the p75 subunit. Patients received up to eight courses of DAB₃₈₉IL-2 given as a short intravenous infusion daily for 5 days with subsequent courses every 21 days. The maximum tolerated dose (MTD) and tumor response was determined according to standard criteria. Seventy-three patients (44 men/29 women), aged 16 to 81 years (mean, 50.7) with CTCL (n = 35), NHL (n = 17), and HD (n = 21) were enrolled. The patients were extensively treated, failing 0 to 15 previous therapies (median, 4). Patients received one to six courses (mean, 3.3) of DAB₃₈₉IL-2 over a range of 3 to 31 μg/kg/day. The dose-limiting toxicity was asthenia, establishing the maximum tolerated dose of 27 μg/kg/day. Approximately half of all patients had significant titers of antibody to diphtheria toxin or to DAB₃₈₉IL-2 at the time of enrollment compared with 92% with titers at the end of treatment. The presence of antibody did not preclude clinical response. There were five complete (CR) and eight partial (PR) remissions in patients with CTCL with one CR and two PR occurring in NHL. The median time to response was 2 months and the duration of response was 2 to 39+ months. No responses were documented in patients with HD. DAB₃₈₉IL-2 is well tolerated with an MTD of 27 μg/kg/day. This ligand fusion-protein showed antitumor effects in patients with IL-2 receptor expressing CTCL and NHL. Additional trials in these diseases are warranted.

Comments

This work was published before the author joined Aga Khan University.

Publication (Name of Journal)

The Journal of the American Society of Hematology

DOI

https://doi.org/10.1182/blood.V91.2.399

Recommended Citation

LeMaistre, C., Saleh, M., Kuzel, T., Foss, F., Platanias, L., Schwartz, G., Ratain, M., Rook, A. (1998). Phase I trial of a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for Interkeukin-2. The Journal of the American Society of Hematology, 91(2), 399-405.
Available at: https://ecommons.aku.edu/eastafrica_fhs_mc_haematol_oncol/112