The Relapse from MRD Negativity As Indication for Treatment (REMNANT) Study
概览
- 阶段
- 2 期
- 干预措施
- Early treatment of relapse with carfilzomib, dexamethasone, daratumumab
- 疾病 / 适应症
- Multiple Myeloma
- 发起方
- Oslo University Hospital
- 入组人数
- 176
- 试验地点
- 13
- 主要终点
- Progression Free Survival (PFS)
- 状态
- 招募中
- 最后更新
- 去年
概览
简要总结
The REMNANT study will evaluate whether treating minimal residual disease (MRD) relapse after first line treatment prolongs progression free survival and overall survival for myeloma patients versus treating relapse after first line treatment at progressive disease. To establish a homogenous group of MRD negative patients after first line treatment including autologous stem cell transplantation, patients are enrolled at diagnosis and treated with Norwegian standard of care first line treatment. MRD negative patients will move on to the randomized part.
详细描述
391 patients with newly diagnosed multiple myeloma eligible for high dose therapy with autologous stem cell support will be included in the phase II part of the study and receive standard of care first line treatment according to Norwegian national guidelines; bortezomib- lenalidomide - dexamethasone for 4 pre-transplant induction and 4 post-transplant consolidation cycles (all 21-d cycles). After induction patients will undergo tandem or single ASCT, depending on toxicity and response to first ASCT. The primary endpoint of the phase 2 part of the study is the number of patients who achieve MRD negative (Euroflow NGF 10 -5 ) complete response 30-45 days post consolidation. Patients (176) achieving MRD negative complete response will be randomly assigned in a 1:1 ratio to receive second line treatment at MRD reappearance (arm A) or at progressive disease as defined by the IMWG criteria (arm B). Randomization will be stratified by R-ISS stage at diagnosis and single vs tandem ASCT. Patients in arm A will be followed with MRD assessment every 4 month and start second line treatment at loss of MRD negative CR. Patients in arm B will be followed up by standard criteria and start second line treatment at progressive disease. Both arms will receive the same 2.L treatment; carfilzomib - dexamethasone - daratumumab. (all 28-d cycles) Second line treatment will continue until disease progression, unacceptable AEs or patient withdrawal. In arm A MRD Euroflow will be assessed after 6 and 18 months of 2L therapy. In arm B MRD Euroflow will be assessed if \>CR is achieved but not before 6 months of 2 L therapy, and again after 12 consecutive months.
研究者
Fredrik Hellem Schjesvold
Head of Oslo Myeloma Center
Oslo University Hospital
入排标准
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm A
Patients will be followed with MRD assessment every 4 month and start 2.L treatment at loss of MRD negative complete response.
干预措施: Early treatment of relapse with carfilzomib, dexamethasone, daratumumab
Arm B
Patients will be followed up by standard criteria and start 2.L treatment at progressive disease.
干预措施: Standard treatment of relapse with carfilzomib, dexamethasone, daratumumab
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: 10 years
Median PFS of Arm A (MRD guided) vs Arm B (PD guided) defined as the time from randomization to disease progression or death due to any cause following 2.L treatment.
Minimal residual disease negativity after first line treatment
时间窗: 30-45 days post consolidation
The number of participants who achieve MRD negativity measured by Euroflow NGF at 30-45 after consolidation therapy has ended
Overall survival (OS)
时间窗: 11 years
Median OS of Arm A vs Arm B (MRD guided) defined as the time from randomization to death of any cause following 2.L treatment.
次要结局
- Minimal residual disease negativity during second line treatment(6 months after starting second line treatment)
- Health-related quality of life (HRQOL)(10 years)
- Time-to-next treatment(10 years)