FeAsiBility of a Treatment Free Interval in Newly Diagnosed mUltiple myeLOma Patients Treated With DaratumUmab-Lenalidomide-DexamethaSone- the FABULOUS Study. A Nationwide Open-label Randomized Phase III Clinical Trial Comparing Daratumumab-lenalidomide-dexamethasone Continuously Versus Including a Treatment Free Interval
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 599
- 试验地点
- 38
- 主要终点
- Compare Progression Free Survival (PFS)
研究概览
简要总结
In the Netherlands, the standard treatment for multiple myeloma is a combination of different medicines named daratumumab-lenalidomide-dexamethasone, abbreviated as Dara-Rd. In many patients this treatment results in suppressing the disease for a long time. The treatment is continued until it is not effective anymore and the disease progresses.
But until now it is unknown whether continuous therapy also leads to prolonging life. In addition, there are concerns about side effects, leading to a reduced quality of life, the development of severe toxicity that remains, which hampers subsequent therapy, and high costs due to prolonged treatment.
There are indications that temporarily stopping treatment is safe, leading to fewer side effects and allows recovering from toxicity or damage due to treatment. This may improve the quality of life.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient was diagnosed with MM, based on the IMWG criteria, and measurable disease at the time of diagnosis (appendix A).
- •Age ≥ 18 years.
- •Patient was treated with 12 cycles (13 cycles is accepted) of Dara-Rd and will continue treatment with Dara-Rd. Reduced dosing of lenalidomide, but not to less than 5 mg, and previous discontinuation or dose reduction of dexamethasone is allowed.
- •Partial response or better after treatment with 12 cycles of Dara-Rd, without signs of biochemical progression.
- •ANC ≥ 1.0x109/L and platelets ≥ 75x109/L.
- •Patient is capable of giving informed consent.
- •Written informed consent.
排除标准
- •Patient with non-secretory MM at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd.
- •Patient in whom a plasmacytoma was the only measurable parameter at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd.
- •Patient in whom urine M-protein was the only measurable parameter at diagnosis of the disease, i.e., before the start of treatment with Dara-Rd.
- •Patient in whom treatment with daratumumab, lenalidomide or both has been discontinued for whatever reason (patients may only have discontinued dexamethasone).
- •Patient in whom continuation of treatment with Dara-Rd is deemed not feasible because of medical reasons.
- •Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
研究组 & 干预措施
Arm B
treatment free interval arm - discontinuation of therapy with Dara-Rd, which will be resumed at biochemical progression and given until PD
干预措施: Daratumumab Injection (Drug)
Arm B
treatment free interval arm - discontinuation of therapy with Dara-Rd, which will be resumed at biochemical progression and given until PD
干预措施: Dexamethasone (Drug)
Arm B
treatment free interval arm - discontinuation of therapy with Dara-Rd, which will be resumed at biochemical progression and given until PD
干预措施: Lenalidomide capsule (Drug)
结局指标
主要结局
Compare Progression Free Survival (PFS)
时间窗: Approximately up to 69 (PFS) months after randomization of the first patient
To compare Progression Free Survival (PFS) from the time of randomization, between arm A continuous therapy with Dara-Rd until PD versus arm B discontinuation of therapy with Dara-Rd, resuming therapy at the first signs of biochemical progression until PD
Compare Event-Free Survival (EFS)
时间窗: Approximately up to 57 (EFS) months after randomization of the first patient
To compare Event-Free Survival (EFS) from the time of randomization, between arm A continuous therapy with Dara-Rd until PD versus arm B discontinuation of therapy with Dara-Rd, resuming therapy at the first signs of biochemical progression until PD
次要结局
- Compare patient-reported outcome measures (PROMs)(Approximately up to 69 months after randomization of the first patient)
- Determine the length of the treatment-free interval(Approximately up to 69 months after randomization of the first patient)
- Determine time to (maximal) response response(Approximately up to 69 months after randomization of the first patient)
- Compare Overall Survival(Approximately up to 69 months after randomization of the last patient)
- Compare dose reductions(Approximately up to 69 months after randomization of the first patient)
- Compare Quality of Life(Approximately up to 69 months after randomization of the first patient)
- Compare adverse event burden(Approximately up to 69 months after randomization of the first patient)
- Compare cost-effectiveness between arms(Approximately up to 69 months after randomization of the first patient)
- Compare time to next treatment(Approximately up to 69 months after randomization of the first patient)
- Compare time from randomization to progression on second-line therapy(Approximately up to 69 months after randomization of the first patient)
- Compare the discontinuation rate(Approximately up to 69 months after randomization of the first patient)
- Evaluate cumulative doses(Approximately up to 69 months after randomization of the first patient)
- Compare relative dose intensity(Approximately up to 69 months after randomization of the first patient)
- Compare toxicity(Approximately up to 69 months after randomization of the first patient)