PAV-trial: Plerixafor and Chemotherapy With Vinorelbine for Stem Cell Mobilization in Patients With Myeloma. A Pilot Phase II Study.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Number of patients from whom ≥ 6 million CD34+ peripheral blood stem cells/kg are harvested in a maximum of 2 days
研究概览
简要总结
High-dose chemotherapy with autologous stem cell support is the current standard procedure in the first-line treatment in younger patients with myeloma fit for intensive treatment. Current practice in Switzerland for stem cell mobilization is the combination of chemotherapy and G-CSF stimulation in myeloma patients fit for high-dose chemotherapy with melphalan and autologous stem cell transplant. In this trial the intravenous application of Plerixafor is being investigated in respect of the capability of the mobilization of stem cells from the bone marrow into the peripheral blood. In contrast to the twice daily application of G-CSF (eg. Neupogen) for several days, Plerixafor has to be injected just one-time.
详细描述
Background
High-dose chemotherapy with autologous stem cell support is the current standard procedure in the first-line treatment in younger patients with myeloma fit for intensive treatment. Current practice in Switzerland for stem cell mobilization is the combination of chemotherapy and G-CSF stimulation in myeloma patients fit for high-dose chemotherapy with melphalan and autologous stem cell transplant. For mobilization chemotherapy, a single dose of vinorelbine is commonly used, producing mild myelosuppression. G-CSF is started at day 4 on a daily basis, allowing stem cell apheresis usually at day 8. In a subsequent study, we evaluated the use of pegylated G-CSF given as a single injection at day 4 together with vinorelbine. We found this regimen equally feasible, reliable and allowing collection of stem cells in an equally high percentage. In the current proposal, we suggest to continue this line of research investigating the mobilization using chemotherapy with vinorelbine. We propose to study the feasibility of this mobilization chemotherapy in the absence of growth factors, thus without G-CSF, in combination with Plerixafor.
Objective
Primary objective: To assess the feasibility of collection of > 6 million CD34+ peripheral blood stem cells/kg body weight in 2 days.
Secondary objectives: Assessment of safety of plerixafor during mobilization and collection of peripheral blood stem cells; feasibility of intravenous plerixafor application and stem cell apheresis in a one-day procedure on an ambulatory basis; evaluation of engraftment of peripheral blood stem cells mobilized by vinorelbine and plerixafor; evaluation of the costs for mobilization with plerixafor.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic stage I or stage II and III myeloma patients after standard first-line non-melphalan containing induction treatment. Patients must be fit for subsequent consolidation with high-dose chemotherapy with melphalan with autologous stem cell support.
- •Standard induction chemotherapy comprises regimens including thalidomide, bortezomib, or lenalidomide (up to 4 cycles), alone or in combination with dexamethasone. Combinations of novel agents are allowed as well as induction with the VAD regimen.
- •Patients must have achieved at least a partial response according to the Bladé criteria after induction chemotherapy.
- •Patient must be aged 18-70 years, with an ECOG < 2 and has given voluntary written informed consent.
- •Platelets count 50 x 109/l without transfusion support within 7 days before the laboratory test.
- •Absolute neutrophil count (ANC) 1.0 x 109/l without the use of colony stimulating factors.
- •Corrected serum calcium < 3 mmol/L.
- •Aspartate transaminase (AST) <= 1.5 x ULN.
- •Alanine transaminase (ALT) <= 1.5 x ULN.
- •Total bilirubin <= 2 x ULN.
- •Creatinin-clearance >= 50 ml/min.
- •Negative pregnancy test within 14 days prior to registration for all women of childbearing potential. Patients of childbearing potential must implement adequate measures to avoid pregnancy during study treatment and for additional 12 months. No pregnant or lactating patients are allowed.
- •Exclusion Criteria
- •Patients previously treated with melphalan or extensive radiotherapy to the bone marrow.
- •Patients with more than 4 cycles of chemotherapy with Lenalidomide.
- •Patients not fit for autologous stem cell transplantation.
- •Patient receiving colony stimulating factors.
- •Patient underwent plasmaphereses within 4 weeks before enrolment.
- •Patient had major surgery within 4 weeks before enrolment.
- •Patient has other serious medical condition that could potentially interfere with the completion of treatment according to this protocol or that would impair tolerance to therapy or prolong hematological recovery.
- •Sero-positive for HIV antibody.
- •Patient known to be hepatitis B surface antigen positive or who has an active hepatitis C infection.
- •Patient has an active systemic infection requiring treatment.
- •Female patient is pregnant or breast feeding.
- •Compromised renal function as evidenced by measured or calculated creatinine clearance <= 50 ml/min.
- •Subject is currently enrolled in, or has not yet completed at least 30 days since ending another investigational device or drug trial or is receiving other investigational agent.
排除标准
- 未提供
研究组 & 干预措施
1
Plerixafor is a bicyclam with hematopoietic stem cell-mobilizing activity. Plerixafor blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4, resulting in hematopoietic stem cell release from bone marrow and HSC movement into the peripheral circulation.
干预措施: Vinorelbine, G-CSF, & Plerixafor (Drug)
1
Plerixafor is a bicyclam with hematopoietic stem cell-mobilizing activity. Plerixafor blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4, resulting in hematopoietic stem cell release from bone marrow and HSC movement into the peripheral circulation.
干预措施: Vinorelbine and Plerixafor (Drug)
1
Plerixafor is a bicyclam with hematopoietic stem cell-mobilizing activity. Plerixafor blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4, resulting in hematopoietic stem cell release from bone marrow and HSC movement into the peripheral circulation.
干预措施: G-CSF and Plerixafor (Drug)
1
Plerixafor is a bicyclam with hematopoietic stem cell-mobilizing activity. Plerixafor blocks the binding of stromal cell-derived factor (SDF-1alpha) to the cellular receptor CXCR4, resulting in hematopoietic stem cell release from bone marrow and HSC movement into the peripheral circulation.
干预措施: Vinorelbine & Plerixafor on day when CD34 count is at least 15'000 CD34+ cells/ml of peripheral blood (Drug)
结局指标
主要结局
Number of patients from whom ≥ 6 million CD34+ peripheral blood stem cells/kg are harvested in a maximum of 2 days
时间窗: day 8 (and 9, if necessary) / 2 days after G-CSF
次要结局
- Proportion of patients with engraftment of PBPC defined as an ANC recovery of ≥ 0.5 x 109/L for 3 consecutive days and a platelet recovery of ≥ 20 x 109/L in the absence of platelet transfusion for at least 7 days(21 months)
- Incidence and severity of adverse events during and after the use of plerixafor(15 days)
- Comparison of costs for mobilization of PBPC with vinorelbine and plerixafor versus the costs for mobilization with vinorelbine and filgrastim and versus the costs for mobilization with vinorelbine and pegfilgrastim(21 Months)