Phase Ⅱ Study of G-CSF, Bortezomib, Cyclophosphamide and Dexamethasone in Patients With Multiple Myeloma
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
RATIONALE: Bortezomib may stop the growth of myeloma cells by blocking proteasome activity. Cyclophosphamide and dexamethasone may work in different ways to stop the growth of myeloma cells by stopping them from dividing or by killing the cells. Granulocyte Clone Stimulating Factor (G-CSF) possesses the ability to mobilize the plasma cells to detach from myeloma niche, so as to promote drug sensitivity.
PURPOSE: This phase Ⅱ trial is to study how well combination of G-CSF, bortezomib, cyclophosphamide and dexamethasone works in treating patients with multiple myeloma.
详细描述
Myeloma cells reside in specialised microenvironments, which is called myeloma niche. Myeloma niche provides important cell-cell interactions and signalling molecules that regulate localization and proliferation of myeloma cells. stromal cell-derived factor 1(SDF-1)/Chemokine (C-X-C Motif) Receptor 4 (CXCR4) plays an important role in this process. G-CSF is reported to induce stem cell mobilization by decreasing bone marrow SDF-1. Our in vitro study found that G-CSF enhanced bortezomib activity by inhibiting SDF-1/CXCR4. Myeloma patients treated with Bortezomib, Cyclophosphamide and Dexamethasone have achieved a relatively good response, with an ORR about 80% and complete remission about 40%. We hypothesized that G-CSF may mobilize myeloma cells from myeloma niches thus to enhance bortezomib activity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, aged ≥18 years, ≤ 80 years.
- •Newly diagnosed multiple myeloma according to International Myeloma Working Group.
- •Relapsed or bortezomib resistant multiple myeloma (MM), who didn't received bortezomib during the last line of therapy for MM prior to this study.
- •Progressive disease according to International Myeloma Working Group.
- •Negative pregnancy test for female with reproductive ability.
- •Signed written informed consent.
排除标准
- •The patient has a history of other active malignancies within 3 years prior to study entry.
- •The patient exhibits evidence of clinically significant uncontrolled conditions including, but not limited to: uncontrolled systemic infection (viral, bacterial, or fungal).
- •Female patient is pregnant or breast-feeding.
- •Known infection with HIV, active Hepatitis B or Hepatitis C.
- •The patient has a history of prior toxicity from bortezomib, cyclophosphamide or dexamethasone that resulted in permanent discontinuation of treatments.
- •Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to study drug administration.
- •Uncontrolled hypertension (defined as systolic blood pressure[BP] > 160 millimeters of mercury (mmHg) or diastolic BP > 100mmHg).
- •Myocardial infarction or unstable angina within the past 6 months prior to study drug administration. Heart failure of New York Heart Association function Class Ⅲ or Ⅳ prior to study drug administration.
- •System illness or other severe concurrent disease or alcoholism, which, in the judgement of the investigator, would make inappropriate for entry into this study or interfere significantly with the proper assessment of safety and efficacy of investigational treatments.
- •Known or suspected of not being able to comply with the trial protocol.
- •Having been previously enrolled in this clinical trial.
研究组 & 干预措施
G-CSF/Bortez/Cyc/Dex
G-CSF IC on days 0, 1, 7, 8, 14, 15, 21 and 22. Bortezomib IV on days 1, 8, 15 and 22. Cyclophosphamide CIV on days 1, 8, 15 and 22. Dexamethasone IV on days 1, 2, 8, 9, 15, 16, 22 and 23.
干预措施: G-CSF (Drug)
G-CSF/Bortez/Cyc/Dex
G-CSF IC on days 0, 1, 7, 8, 14, 15, 21 and 22. Bortezomib IV on days 1, 8, 15 and 22. Cyclophosphamide CIV on days 1, 8, 15 and 22. Dexamethasone IV on days 1, 2, 8, 9, 15, 16, 22 and 23.
干预措施: Bortezomib (Drug)
G-CSF/Bortez/Cyc/Dex
G-CSF IC on days 0, 1, 7, 8, 14, 15, 21 and 22. Bortezomib IV on days 1, 8, 15 and 22. Cyclophosphamide CIV on days 1, 8, 15 and 22. Dexamethasone IV on days 1, 2, 8, 9, 15, 16, 22 and 23.
干预措施: Cyclophosphamide (Drug)
G-CSF/Bortez/Cyc/Dex
G-CSF IC on days 0, 1, 7, 8, 14, 15, 21 and 22. Bortezomib IV on days 1, 8, 15 and 22. Cyclophosphamide CIV on days 1, 8, 15 and 22. Dexamethasone IV on days 1, 2, 8, 9, 15, 16, 22 and 23.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 4 months
Defined as the portion of patients whose best response is equal to or better than partial response (PR), including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) according to International Myeloma Working Group (IMWG). Response was confirmed after every cycle of treatment. Stringent complete response (sCR): Normal free light chain (FLC) ration, plus criteria for complete response. Complete response (CR): Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and ≤ 5% plasma cells in the bone marrow. Very Good Partial Response(VGPR): Positive immunofixation but negative electrophoresis; ≥90% reduction in serum M-component; Urine M-component ≤ 100mg per 24 hours. Partial Response (PR): ≥50% reduction in serum M-component and/or Urine M-component ≥90% reduction or \< 200mg per 24 hours.
次要结局
- Number of participants with treatment related adverse events.(participants will be followed for the duration of hospital stay, an expected average of 4 weeks)
- Overall Survival (OS)(2 years)
- Progression Free Survival (PFS)(2 years)
- Duration of Response (DOR)(2 years)
研究者
jinxiang fu
M.D., Ph.D.
Second Affiliated Hospital of Soochow University