NCT00500058已完成1 期
A Phase I, Dose-Escalation Study to Assess the Safety and Biological Activity of Recombinant Human Interleukin-18 (SB-485232) Administered by Intravenous Infusion in Combinationwith Rituximab in Adult Patients With B Cell Non-Hodgkin'sLymphoma"
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- safety/tolerability of combination treatment for 4 weeks safety/tolerability of SB-485232 for additional 8 weeks
研究概览
简要总结
The purpose is to identify a dose of SB-485232 which is safe, tolerable and effective when used in combination with Rituximab in patients with non-Hodgkin's lymphoma (NHL). This study will use a standard treatment regimen of Rituximab in combination with rising doses of SB-485232. The dose selected from this study will be used in a future studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed diagnosis of any subtype of CD20+ B cell NHL. Subjects must have disease that progressed after standard therapy or for which there is no effective standard therapy (including high-dose therapy and autologous stem cell transplantation). NOTE: If the subject has had a prior autologous stem cell transplant, it must have occurred at least three months prior to screening and the subject must be fully recovered from any acute toxicities.
- •Prior treatment with Rituximab is allowed, provided it was completed at least six months before study enrollment.
- •Male or female ≥ 18 years of age.
- •Measurable or evaluable disease.
- •Predicted life expectancy of at least 12 weeks.
- •ECOG Performance Status of 0 or
- •No chemotherapy, immunotherapy, hormonal therapy, or biological therapy for cancer, radiotherapy, or surgical procedures (except for minor surgical procedures) within four weeks before beginning treatment with SB-485232 (6 weeks for nitrosoureas and mitomycin C). Subjects must have recovered from toxicities (incurred as a result of previous therapy) sufficiently to be entered into a Phase I study.
- •A signed and dated written informed consent form is obtained from the subject.
- •The subject is able to understand and comply with protocol requirements, timetables, instructions and protocol-stated restrictions.
- •The subject is likely to maintain good venous blood access for PK and PD sampling throughout the study.
- •A female is eligible to enter and participate in the study if she is of:
- •a. non-childbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who:
- •has had a hysterectomy,
- •has had a bilateral oophorectomy (ovariectomy),
- •has had a bilateral tubal ligation,
- •is post-menopausal (demonstrate total cessation of menses for greater than 1year), If amenorrheic for less than one year, post-menopausal status will be confirmed by serum follicle stimulating hormone (FSH) and oestradiol concentrations at screening. or, b. childbearing potential, has a negative serum pregnancy test at the Screen Visit, and agrees to one of the following GSK acceptable contraceptive methods:
- •any intrauterine device (IUD) with a documented failure rate of less than
- •1% per year.
- •vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female.
- •oral contraceptive (either combined or progesterone only).
- •because of the unacceptable failure rate of barrier (chemical and/or physical) methods, the barrier method of contraception must only be used in combination with other acceptable methods described above.
- •Adequate organ function,
排除标准
- •Women who are pregnant or are breast-feeding.
- •Significant cardiac, pulmonary, metabolic, renal, hepatic, gastrointestinal or autoimmune conditions that in the opinion of the investigator and/or GSK medical monitor, places the subject at an unacceptable risk as participant in this trial.
- •The subject has diabetes mellitus with poor glycemic control.
- •The subject has a history of human immunodeficiency virus (HIV) or other immunodeficiency disease.
- •The subject has positive Hepatitis B surface antigen.
- •Corrected QT interval (QTc) > 480msec.
- •The subject has a history of a severe infusion related reaction or tumor lysis syndrome following treatment with Rituximab (Section 10.2.2).
- •The subject has a circulating malignant cell count > 25,000/mm3 in peripheral blood.
- •The subject has known anaphylaxis or IgE-mediated hypersensitivity to murine proteins.
- •The subject has an acute infection or severe or uncontrolled infections requiring systemic antibiotic therapy.
- •Any serious medical or psychiatric disorder that would interfere with subject safety or informed consent.
- •Known leptomeningeal disease or evidence of prior or current metastatic brain disease. Routine screening with central nervous system (CNS) imaging studies (CT or MRI) is required only if clinically indicated.
- •Receiving concurrent chemotherapy, immunotherapy, radiotherapy, or investigational therapy.
- •Oral corticosteroids within 14 days of study entry.
- •History of alcohol abuse within six months of screening or alcohol consumption in the past six months exceeding seven drinks/week for women and 14 drinks/week for men (where 1 drink = 5 ounces of wine or 12 ounces of beer or 1.5 ounces of hard liquor).
- •History of ventricular arrhythmias requiring drug or device therapy.
- •Any unresolved or unstable serious toxicity from prior administration of another investigational drug.
- •Any investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of SB-
- •Donation of blood in excess of 500 mL within a 56-day period prior to dosing.
研究组 & 干预措施
SB-485232+Rituximab
Experimental
Rituximab 375 milligrams per square meter (mg/m^2) will be administered to subjects with CD20+ B cell lymphoma by intravenous (IV) infusion once a week for four consecutive weeks on Day 1 of Weeks 1 to 4. SB-485232 will be administered by IV infusion over a 2 hour period, at doses ranging from 1 microgram (μg)/kilogram (kg) to 100 μg/kg. SB-485232 will be given once a week for 12 consecutive weeks on Day 2 of Weeks 1 to 4 and Day 2 (± 1 day) of Weeks 5 to 12. SB-485232 will be infused at least 24 hours after the Rituximab infusion was started.
干预措施: SB-485232 (Drug)
SB-485232+Rituximab
Experimental
Rituximab 375 milligrams per square meter (mg/m^2) will be administered to subjects with CD20+ B cell lymphoma by intravenous (IV) infusion once a week for four consecutive weeks on Day 1 of Weeks 1 to 4. SB-485232 will be administered by IV infusion over a 2 hour period, at doses ranging from 1 microgram (μg)/kilogram (kg) to 100 μg/kg. SB-485232 will be given once a week for 12 consecutive weeks on Day 2 of Weeks 1 to 4 and Day 2 (± 1 day) of Weeks 5 to 12. SB-485232 will be infused at least 24 hours after the Rituximab infusion was started.
干预措施: Rituximab (Drug)
结局指标
主要结局
safety/tolerability of combination treatment for 4 weeks safety/tolerability of SB-485232 for additional 8 weeks
时间窗: 12 weeks
次要结局
- Activated Neutrophils/Monocytes (CD11b+/CD16+/CD64+/CD14+/CD45+/CD69+)(12 weeks)
- Immunogenicity (anti-SB-485232 and anti-Rituximab antibodies)(12 weeks)
- Pharmacodynamic biomarker responses:(12 weeks)
- Anti-tumor activity (Radiographic tumor assessments)(12 weeks)
- CD16 (FcγRIIIA) 158V/F genotyping(12 weeks)
- assess blood values of combination treatment for 4 weeks assess blood values of SB-485232 for additional 8 weeks(12 weeks)
- Pharmacokinetic parameters for SB-485232 and Rituxan: AUCtau, Cmax, and Cmin.(12 weeks)
- PBMC phenotype changes(from baseline and pre-dose)
- Activated NK cells (CD16+/CD56+/CD3-/CD69+/FasL+ or IL-18Ra+)(12 weeks)
- Plasma IL-18BP change(from baseline)
- Plasma IFN-γ, GMCSF, IP-10, MIG, and MCP-1 changes(from baseline and predose)
- Activated cytolytic T cells (CD8+/CD4-/CD3+/CD69+ FasL+ or IL- 18Ra+)(12 weeks)
- Activated B cells (CD19+/CD25-/CD3-/CD69+)(12 weeks)
- Regulatory T-cells (FoxP3+/CD25+/CD4+/CD127+)(12 weeks)
研究者
研究点 (1)
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