A Randomized Phase III Study to Compare Bortezomib, Melphalan, Prednisone (VMP) With High Dose Melphalan Followed by Bortezomib, Lenalidomide, Dexamethasone (VRD) Consolidation and Lenalidomide Maintenance in Patients With Newly Diagnosed Multiple Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,503
- 试验地点
- 208
- 主要终点
- For all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first
研究概览
简要总结
Study phase: phase III
Study objective:
- Comparison of Bortezomib, Melphalan, Prednisone (VMP) with High Dose Melphalan followed autologous stem cell transplantation (ASCT)
- Comparison of Bortezomib, Lenalidomide, Dexamethasone(VRD) as consolidation versus no consolidation
- Comparison of single versus tandem high dose Melphalan with ASCT
Patient population: Patients with symptomatic multiple myeloma,previously untreated, ISS stages 1-3, age 18-65 years inclusive
Study design: Prospective, multicenter, intergroup, randomized
Duration of treatment: Expected duration of induction, stem cell collection and intensification is 6 - 9 months. Consolidation with VRD will last 2 months Maintenance therapy with Lenalidomide will be given until relapse. All patients will be followed until 10 years after registration.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a confirmed diagnosis of symptomatic multiple myeloma stage I to III according to the International Staging System ISS (see appendix A), i.e. at least one of the CRAB criteria should be present;
- •Measurable disease as defined by the presence of M-protein in serum or urine (serum M-protein> 10 g/l or urine M-protein > 200 mg/24 hours), or abnormal free light chain ratio;
- •Age 18-65 years inclusive;
- •WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by comorbid conditions);
- •Negative pregnancy test at inclusion if applicable;
- •Written informed consent.
- •Inclusion for randomisation 1:
- •WHO performance 0-2;
- •Bilirubin and transaminases < 2.5 times the upper limit of normal values;
- •A suitable stem cell graft containing at least 4 x 106 CD34+ cells/kg (or according to national guidelines).
- •Inclusion for randomisation 2:
- •Bilirubin and transaminases < 2.5 times the upper limit of normal values;
- •ANC >= 0.5 x 109/l and platelets > 20 x 10^9/l;
- •Patient is able to adhere to the requirements of the Lenalidomide Pregnancy Prevention Risk Management Plan.
排除标准
- •Known intolerance of Boron;
- •Systemic AL amyloidosis;
- •Primary Plasmacell Leukemia;
- •Non-secretory MM;
- •Previous chemotherapy or radiotherapy except local radiotherapy in case of local myeloma progression or corticosteroids maximum 5 days for symptom control;
- •Severe cardiac dysfunction (NYHA classification II-IV);
- •Significant hepatic dysfunction, unless related to myeloma;
- •Patients with GFR <15 ml/min,
- •Patients known to be HIV-positive;
- •Patients with active, uncontrolled infections;
- •Patients with neuropathy, CTC grade 2 or higher;
- •Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
- •Patients who are not willing or capable to use adequate contraception during the therapy (all men, all pre-menopausal women);
- •Lactating women.
- •Exclusion for randomisation 1:
- •Severe pulmonary, neurologic, or psychiatric disease;
- •CTCAE grade 3-4 polyneuropathy during Bortezomib treatment;
- •Allogeneic Stem Cell Transplantation (Allo SCT) planned;
- •Progressive disease.'
- •Exclusion for randomisation 2:
- •Progressive disease;
- •Neuropathy, except CTCAE grade 1;
- •CTCAE grade 3-4 polyneuropathy during Bortezomib treatment.
研究组 & 干预措施
R2: none
No consolidation, patients will continue to Lenalidomide maintenance.
R1: 4 cycles Bortezomib, Melphalan, Prednisone (VMP)
All patients randomized to VMP treatment, will be treated with Bortezomib, Melphalan, Prednisone(VMP, 4 cycles) and will start intensification with VMP between 4 and 6 weeks after stem cell collection.
干预措施: Bortezomib, Melphalan, Prednisone (VMP) (Drug)
R1: 1 (2) cycle(s) HDM
All patients randomized to intensification with High Dose Melphalan will start intensification with HDM (in hospitals with a policy of double intensification, patients will be randomized between VMP, 1 HDM and 2 HDM) between 4 and 6 weeks after stem cell collection.
干预措施: 1 or 2 cycle(s) HDM (High Dose Melphalan) (Drug)
R2: 2 cycles of VRD
In patients randomized to consolidation treatment, 2 cycles of Bortezomib, Lenalidomide,Dexamethasone (VRD) will start at 8 weeks after the end of the last course of VMP or HDM.
干预措施: 2 cycles of Bortezomib, Lenalidomide, Dexamethasone (VRD) (Drug)
结局指标
主要结局
For all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first
时间窗: end of trial (last patient last visit)
For all patients included in R1; PFS as defined by time from randomization R1 to progression or death from any cause whichever comes first
For all registered patients: progression free survival (PFS) as defined by time from registration to progression or death from any cause (whichever occurs first).
时间窗: end of trial (last patient last visit)
For all registered patients: progression free survival (PFS) as defined by time from registration to progression or death from any cause (whichever occurs first).
For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes first
时间窗: end of trial (last patient last visit)
For all patients included in R2; PFS as defined by time from randomization R2 to progression or death from any cause whichever comes first
次要结局
- Response (PR, VGPR, CR and stringent CR), and improvement of response during the various stages of the treatment.(end of trial (last patient last visit))
- Overall survival measured from the time of registration /randomization R1/ randomization R2. Patients still alive or lost to follow up are censored at the date they were last known to be alive.(end of trial (last patient last visit))
- Toxicity(End of trial (last patient last visit))