A phase I study of recombinant human soluble interleukin-1 receptor (rhu IL-1R) in patients with relapsed and refractory acute myeloid leukemia

Purpose: The recombinant human interleukin-1 receptor (rhu IL-1R) is a solu ble truncated form of the type 1 full-length membrane-bound receptor that b inds IL-1 with identical affinity to that of the membrane form. As such, it may have clinical potential by sequestering IL-1, thereby preventing it fr om binding to its membrane-bound receptor and eliciting a biological effect . As IL-1 has been shown to regulate leukemic cell proliferation in an auto crine fashion, a phase I trial of rhu IL-1R was conducted in patients with relapsed and refractory acute myeloid leukemia (AML). Methods: The study gr oup comprised 11 patients who were sequentially treated on one of three dos e levels, receiving a single intravenous (i.v.) bolus dose on day 1 followe d by 13 days of daily subcutaneous (s.c.) injections with the option of an additional 14 days of treatment if a response of stable disease or better w as achieved. Dose level 1 i.v. bolus 500 mu g/m(2), s.c, dose 250 mu g/m(2) per day (five patients); dose level 2 i.v. bolus 1000 mu g/m(2), s.c. doss 500 mu g/mL per dap (three patients); dose level 3 i.v. bolus 2000 mu g/m( 2), s.c. dose 1000 mu g/m(2) per day (three patients). Owing to limited dru g availability, the study was designed to only examine these three dose lev els. Results: rhu IL-1R was well tolerated. There was no grade 3 or 3 non-h ematological toxicity related to the study drug and the maximum tolerated d ose was not reached. No IL-1R-blocking antibodies developed during the cour se of the study. Serum levels of IL-1 beta, IL-6 and TNF were undetectable before, during and after rhu IL-1R administration. The terminal half-life a fter i.v. dosing was at least 7-12 h, and after s.c. dosing 2-4 days. Serum levels of rhu IL-1R up to 360- and 25-fold those of pretreatment levels we re achieved after i.v. and s.c. dosing respectively. No patient had a compl ete, partial or minor response to treatment; four had stable disease and se ven had progressive disease. Conclusions: rhu IL-1R therapy was safe but di d not have any apparent antileukemic effect at the doses administered.