Multicenter, randomized study of genetically modified recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in cancer patients receiving chemotherapy.

ABSTRACT

PURPOSE: The aim of this study is to evaluate the efficacy and safety of genetically modified recombinant human IL-11 (mIL-11), using original IL-11 as an active control, in a multicenter randomized trial involving 88 cancer patients undergoing chemotherapy METHODS: Eighty-eight subjects who had platelets ≤ 75 × 10(9)/L during the prior chemotherapy were randomized to the MR or RM group. Cohort MR consists of subcutaneous injection of mIL-11 (7.5 µg/kg/day) for 10 days, beginning 72 h after chemotherapy for a 21-day chemotherapy cycle (cycle-1) followed by that of recombinant human interleukin-11 (rhIL-11) (25 µg/kg/day) for another 10 days (cycle-2). Cohort RM represents the reverse sequence. Intent-to-treat populations of mIL-11 (n = 73) or rhIL-11 (n = 80) were analyzed to evaluate the safety. RESULTS: The incidence of drug-related adverse events of mIL-11 (32.9%) was lower than that of rhIL-11 (51.3%) (p = 0.033). There were no unexpected ≥ grade-3 adverse events, and no subject developed antibodies to the mIL-11 protein. Sixty-two subjects were analyzed for efficacy by measuring average platelet levels. Both mIL-11 and rhIL-11 increased nadir platelet levels (62.6 ± 34.9 × 10(9)/L for mIL-11 vs. 60.2 ± 31.7 × 10(9)/L for rhIL-11) as compared with the untreated control group (41.2 ± 17.7 × 10(9)/L) (p < 0.0001). There was no statistical difference in average platelet levels and platelet recovery rate between mIL-11 and rhIL-11. CONCLUSIONS: This study shows that mIL-11 is well tolerated and has thrombopoietic activity equivalent to one third of the clinical dose of rhIL-11, indicating the potential of mIL-11 for use in the treatment of CIT.