Randomised Phase II Study Evaluating the Anti-tumour Activity, Safety and Pharmacology of Two Dose Regimens of IPH2101, a Human Monoclonal Anti-KIR Antibody, in Patients With Multiple Myeloma in Stable Partial Response After a First Line Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 27
- 试验地点
- 9
- 主要终点
- Rate of Patients Achieving a Response Based on M-protein or Free Light Chains
研究概览
简要总结
This is an open randomised phase II study evaluating the anti-tumour activity, safety and pharmacology of two dose regimens of IPH2101, a human monoclonal anti-KIR antibody, in patients with multiple myeloma in stable partial response after a first line therapy.
详细描述
Development of new treatments for diseases such as multiple myeloma is a focus for research. The research being conducted is on treatment called Anti-KIR, which activates the body's own cells to kill tumor cells. This is different from many other treatments where chemicals are given to kill tumor cells.The primary objective of the study is to evaluate the clinical activity of two different dose regimens (0.2 mg/kg, leading to an intermittent saturation of NK receptors and 2mg/kg leading to a sustained saturation of NK receptors) of IPH2101 administered as a single agent in multiple myeloma patients who achieved, after the completion of any first line treatment, including conventional or high dose chemotherapies, a stable partial or very good partial response (PR or VGPR).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •MM which initially required a systemic therapy and received a first line treatment, conventional doses of chemotherapies or high dose chemotherapy and an autologous transplantation of hematopoietic cells, followed or not by a consolidation treatment.
- •Residual disease considered as evaluable with:
- •Quantifiable serum M-protein: ≥ 3 g/l, except for spike in the beta globulin area. In this particular case serum M-protein is considered quantifiable if ≥ 10g/l
- •If serum M-protein is < 3g/l, measurable involved Free Light Chains ≥ 100 mg/l and an abnormal Free Light chains ratio (<0.26 or > 1.65)
- •Responses which are partial (PR and VGPR) and in plateau
- •Partial response should meet the IMWG uniform response criteria: a ≥ 50% reduction from value of serum M-protein before the first line chemotherapy treatment and a reduction in 24h urinary M-protein by ≥ 90% or to < 200 mg /24h;
- •Very good partial response according to the IMWG uniform response criteria with 90% or greater reduction in serum M-protein plus urine M-protein level < 100 mg/24h; furthermore the M-protein should spike in the gamma globulin area;
- •Plateau phase is defined by :
- •For patients with serum M-protein ≥ 3g/l: stable levels of M-protein in serum during at least 2 months checked on at least 3 consecutive samples, with the third evaluation performed within 4 weeks before study entry. Fluctuations of ± 25 % and ± 2 g/l in Serum M-protein levels are allowed.
- •For Patients with serum M-protein < 3g/l: stable levels Free Light Chains in serum during at least 2 months checked on at least 3 consecutive samples, with the third evaluation performed within 4 weeks before study entry. Fluctuations of ± 25 % of involved serum Free Light Chain are allowed.
- •ECOG performance status of 0, 1 or
- •Clinical laboratory values at screening:
- •Calculated creatinine clearance (according to MDRD) > 50 ml/min
- •Platelet > 50 x 109 /l
- •ANC > 1 x 109 /l
- •Bilirubin levels < 1.5 ULN; ALT and AST < 2.5 ULN
- •Male or female patient who accepts and is able to use recognised effective contraception (oral contraceptives, IUCD, barrier method of contraception in conjunction with spermicidal jelly) throughout the study.
- •Signed inform consent obtained before any trial-related activities
排除标准
- •Age < 18 years old or > 75 years old
- •Previous consolidation/ maintenance therapy by Imid (thalidomide, lenalidomid) or bortezomib within the last 2 months
- •Treatment with chemotherapy, systemic corticosteroid within the previous 2 months
- •Treatment with growth factors (EPO, G- or GM-CSF) within the previous 1 month
- •Radiotherapy for bone or visceral lesion within the last 3 months
- •Use of any investigational agent within the last 2 months
- •Primary or associated amyloidosis
- •Peripheral neuropathy of grade ≥ III according to the CTCAE of the NCI
- •Abnormal cardiac status with any of the following
- •NYHA stage III or IV congestive heart failure
- •myocardial infarction within the previous 6 months
- •symptomatic cardiac arrhythmia despite treatment
- •Current active infectious disease or positive serology for HIV, HCV or positive Hbs Antigen
- •History of or current auto-immune disease
- •Serious concurrent uncontrolled medical disorder
- •History of other malignancy for less then 5 years (apart from basal cell carcinoma of the skin, or in situ cervix carcinoma)
- •History of allogenic hematopoietic cell or solid organ transplantation
- •Pregnant or lactating women
- •Any medical condition which is regarded by the investigator as incompatible with the study participation
- •Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
研究组 & 干预措施
IPH 2101 0.2 mg/kg
One infusion of IPH2101 every 4 weeks at the dose of 0.2 mg/kg by intravenous route over 1 hour, for 4 or up to 8 cycles.
干预措施: IPH2101 (Drug)
IPH2101 2.0 mg/kg
One infusion of IPH2101 every 4 weeks at the dose of 2 mg/kg by intravenous route over 1 hour, for 4 or up to 8 cycles.
干预措施: IPH2101 (Drug)
结局指标
主要结局
Rate of Patients Achieving a Response Based on M-protein or Free Light Chains
时间窗: From the start of the treatment to the End of Study and during the post study follow up during 2 years according to standard practices
Response was defined: * In patients with a serum M-protein \> 5 g/l, as a reduction of at least 25% (minor response according to European society for Blood and Marrow Transplantation (EBMT)) from baseline of serum M-protein confirmed on two consecutive determinations at 4 weeks interval; * In patients with a serum M-protein ≤ 5 g/l and ≥ 3g/l, as a negative electrophoresis * In patients with serum M-protein \< 3 g/l but a measurable involved serum free light chains ≥ 100 mg/l and an abnormal Free Light Chains ratio (\<0.26 or \> 1.65), as a ≥ 50 % decrease in the difference between involved and uninvolved Free Light Chains levels.
次要结局
- Biological Activity of IPH2101 on Killer Immunogloblin Like Receptors (KIR) Occupancy at End of Treatment(From the start up to the end of study (15 months))
- Safety Assessment(from screening visit to the End of Study (at each study visit))