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.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Thrombocytopenia
• Intervention / Treatment: Drug: NL201; Drug: NL201; Drug: NL201; Drug: rhIL-11

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Cancer Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • The Third Affiliated Hospital of Harbin Medical University
  • Jilin
    • Changchun, Jilin, China
      • The First Hospital of Jilin University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
  • Tianjin
    • Tianjin, Tianjin, China
      • Tianjin Medical University Cancer Institute and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A1; 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.	Drug: NL201; mIL-11:5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy； Other Names: mIL-11; Drug: NL201; mIL-11:7.5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy； Other Names: mIL-11; Drug: NL201; The optimal dosing dose NL201，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.; Other Names: mIL-11
Experimental: A2; 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.	Drug: NL201; mIL-11:5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy； Other Names: mIL-11; Drug: NL201; mIL-11:7.5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy； Other Names: mIL-11; Drug: NL201; The optimal dosing dose NL201，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.; Other Names: mIL-11
Active Comparator: A; 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.	Drug: NL201; mIL-11:5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy； Other Names: mIL-11; Drug: NL201; mIL-11:7.5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy； Other Names: mIL-11; Drug: NL201; The optimal dosing dose NL201，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.; Other Names: mIL-11; Drug: rhIL-11; rhIL-11(25μg/kg)，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.; Other Names: Recombinant Human Interleukin-11 for Injection
Active Comparator: B; 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.	Drug: NL201; mIL-11:5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy； Other Names: mIL-11; Drug: NL201; mIL-11:7.5μg/kg，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy； Other Names: mIL-11; Drug: NL201; The optimal dosing dose NL201，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.; Other Names: mIL-11; Drug: rhIL-11; rhIL-11(25μg/kg)，subcutaneous administration once daily for 10 days,beginning 24 h after chemotherapy.; Other Names: Recombinant Human Interleukin-11 for Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: Beijing Northland Biotech. Co., Ltd.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): August 1, 2017

Study Registration Dates

• First Submitted: August 9, 2012
• First Submitted That Met QC Criteria: August 10, 2012
• First Posted (Estimate): August 13, 2012

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Chemotherapy; Platelet; Thrombocytopenia; Interleukin-11
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Platelet Disorders; Thrombocytopenia; Antineoplastic Agents; Oprelvekin
• Other Study ID Numbers: NL201-Ⅲ-2012