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

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.

• NL201 (Drug), also known as mIL-11: mIL-11:5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy；
• NL201 (Drug), also known as mIL-11: mIL-11:7.5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy；
• NL201 (Drug), also known as mIL-11: The optimal dosing dose NL201，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.
• rhIL-11 (Drug), also known as Recombinant Human Interleukin-11 for Injection: rhIL-11(25μg/kg)，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.

Primary outcomes

• Recovery time of platelet counts from below 100x10^9/L raise to more than 100 x10^9/L. [During 21 days of chemotherapy cycles]

Secondary outcomes

• Nadir platelet counts [During 21 days of chemotherapy cycles]
• Platelet counts at day 21 after the initiation of chemotherapy. [Day 21 after the initiation of chemotherapy.]
• Average platelet counts [During 21 days of chemotherapy cycles]
• Incidence of thrombocytopenia [During 21 days of chemotherapy cycles]

Sex: All, ages: 18 Years to 75 Years

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