A Phase Ⅲa Study of Genetically Modified Recombinant Human Interleukin-11

Multicenter, Randomized Phase Ⅲa Study of Genetically Modified Recombinant Human Interleukin-11 to Prevent Chemotherapy-induced Thrombocytopenia in Cancer Patients Receiving Chemotherapy.

This phases Ⅲ trials is divided into two stages,Ⅲa and Ⅲb.The aim of Ⅲa is to evaluate the optimal dosing dose of genetically modified recombinant human IL-11 (mIL-11) in a multicenter randomized self-control trial involving 60 cancer patients undergoing chemotherapy.The aim of Ⅲb is to evaluate the efficacy and safety of genetically modified recombinant human IL-11 (mIL-11), using rhIL-11 as an active control, in a multicenter randomized trial involving 240 cancer patients undergoing chemotherapy.

The investigators recently developed a mutant form of rhIL-11 with improved stability. In in vitro experimental systems, mIL-11 was shown to endure chemical and proteolytic stresses more effectively, while retaining the biological activity of the original rhIL-11. The improved stability of mIL-11 was also demonstrated in the comparative pharmacokinetic study of subcutaneously delivered mIL-11 and rhIL-11 in the rodent and primate models. Based on its improved pharmacokinetic and pharmacodynamic features. In Phase II 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. This study is a phase III, single-blinded, randomized,multicenter,cross-over study designed to evaluate optimal dosing dose and efficacy and safety of mIL-11 on CIT patients receiving suitable chemotherapeutic regimen for treating cancer.

Patients in this treatment group will receive NL201(5μg/kg) in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive NL201(7.5μg/kg). Only for Dose-finding in Phase Ⅲa.

Patients in this treatment group will receive NL201(7.5μg/kg) in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive NL201(5μg/kg). Only for Dose-finding in Phase Ⅲa.

Patients in this treatment group will receive NL201（optimal dosing dose）in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive rhIL-11(25μg/kg). Only in Phase Ⅲb.

Patients in this treatment group will receive rhIL-11(25μg/kg) in the first Chemotherapy cycle.Then，in the second Chemotherapy cycle，receive NL201（optimal dosing dose）. Only in Phase Ⅲb.

mIL-11:7.5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy；

The optimal dosing dose NL201，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.

rhIL-11(25μg/kg)，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.

Inclusion Criteria: histological verification of malignancy at the time of initial diagnosis； Patients (age,18-75 years) receiving chemotherapy, who had experienced platelet counts below 75×10^9/L； patients were required to have adequate bone marrow,hepatic, and renal functions at the time of study entry； ECOG ≤2； patients to have normal laboratory findings:while white blood count >3.0×10^9/L,platelet count ≥100×10^9/L, and AST and/or ALT lesser than 2.5 times the upper limit of the normal value； The estimated life expectancy of the patient was more than 3 months. Exclusion Criteria:； patients who received total body irradiation； patients with childbearing potential； patients who were breast-feeding or pregnant