Myeloma XIV: A Phase III Trial to Compare Standard and Frailty-adjusted Induction Therapy With Ixazomib, Lenalidomide and Dexamethasone (IRD) and Maintenance Lenalidomide (R) to Lenalidomide Plus Ixazomib (R+I)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 740
- 试验地点
- 110
- 主要终点
- Randomisation 1: Number of participants with early treatment cessation
研究概览
简要总结
Trial Title:
FiTNEss (UK-MRA Myeloma XIV) - Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma
Overview:
A phase III, multi-centre, randomised controlled trial to compare standard (reactive) and frailty-adjusted (adaptive) induction therapy delivery with the novel triplet ixazomib, lenalidomide and dexamethasone (IRD), and to compare maintenance lenalidomide (R) to lenalidomide plus ixazomib (R+I) in patients with newly diagnosed multiple myeloma not suitable for a stem cell transplant.
All participants receive induction treatment with ixazomib, lenalidomide and dexamethasone and are randomised on a 1:1 basis at trial entry to the use of frailty score-adjusted up-front dose reductions vs. standard up-front dosing followed by toxicity dependent reactive dose-modifications during therapy. Following 12 cycles of induction treatment participants alive and progression-free undergo a second randomisation on a 1:1 basis to maintenance treatment with lenalidomide plus placebo versus lenalidomide plus ixazomib. Participants and their treating physicians will be blinded to maintenance allocation.
Participant population:
- Newly diagnosed as having Multiple Myeloma (MM) according to the updated IMWG diagnostic criteria 2014 (see Appendix 1 for criteria)
- Not eligible for stem cell transplant
- Aged at least 18 years
- Able to provide written informed consent
Number of participants:
740 participants will be entered into the trial at Randomisation 1 (R1), with 478 participants at Randomisation 2 (R2).
Objectives:
The primary objectives of this study are to determine:
- Early treatment cessation (within 60 days of randomisation) for standard versus frailty-adjusted up-front dosing
- Progression-free survival (PFS, from maintenance randomisation) for lenalidomide + placebo (R) versus lenalidomide + ixazomib (R+I)
The secondary objectives of this study are to assess progression-free survival (PFS) for standard versus frailty-adjusted up-front dosing reductions, time to progression, time to 2nd PFS event (PFS2), overall survival (OS), survival after progression, deaths within 12 months of R1, overall response rate (ORR), attainment of ≥VGPR, attainment of MRD negativity, duration of response, time to improved response, time to next treatment, treatment compliance and total amount of therapy delivered, toxicity & safety including the incidence of SPMs, Quality of Life (QoL), cost effectiveness of standard versus frailty-adjusted up-front dosing of IRD and cost-effectiveness of R + I versus R.
Exploratory objectives are prospective validation of a novel frailty risk score (UK-MRA Myeloma Risk Profile - MRP), usefulness of Karnofsky Performance Status (PS), and association of molecular subgroups with response, PFS and OS.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Randomisation 1 is open label Randomisation 2 is double-blind, placebo-controlled
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
- 未提供
排除标准
- 未提供
结局指标
主要结局
Randomisation 1: Number of participants with early treatment cessation
时间窗: Within 60 days of Randomisation 1
Early treatment cessation is defined as a binary endpoint. Participants will be defined to have experienced an event if they die, progress, or are withdrawn from treatment (by a treating clinician) or withdraw consent for trial treatment, within 60 days of Randomisation 1.
Randomisation 2: Progression-free survival (PFS-R2)
时间窗: The time from the date of Randomisation 2 to the date of first documented evidence of disease progression or death from any cause, up to 120 months
PFS-R2 is defined as the time from Randomisation 2 to the time of first documented evidence of disease progression or death from any cause. Individuals who are lost to follow-up or progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. Disease progression is defined according to the IMWG Uniform Response Criteria for Multiple Myeloma.
次要结局
- Deaths within 12 months of Randomisation 1 (R1)(Within 12 months of Randomisation 1)
- Progression-free survival (PFS-R1)(The time from the date of Randomisation 1 to the date of first documented evidence of disease progression or death from any cause, up to 120 months)
- Overall response rate (ORR)(From the date of Randomisation 1 to the end of 12 cycles of induction treatment (each induction cycle is 28 days))
- Duration of response (DoR)(The time from the date of the first observation of response ≥ Partial Response following Randomisation 1, to the date of first documented evidence of disease progression or death confirmed related to progression, up to 120 months)
- Overall survival (OS)(The time from the date of randomisation to the date of death from any cause, up to 120 months)
- Survival after progression(The date of first documented evidence of disease progression to the date of death from any cause, up to 120 months)
- Time to disease progression(The time from the date of randomisation to the date of first documented evidence of disease progression, up to 120 months)
- Progression-free survival two (PFS2)(The time from the date of randomisation to the date of the second documented disease progression, up to 120 months)
- Attainment of Minimal Residual Disease (MRD) negativity(From the date of Randomisation 1 to the end of 12 cycles of induction treatment (each induction cycle is 28 days); and 12 months after the date of Randomisation 2)
- Treatment compliance and total amount of therapy delivered(Number of induction and maintenance cycles a participant received (each cycle of induction or maintenance is 28 days), until disease progression, up to 120 months)
- EORTC QLQ-C30_questionnaire(Randomisation 1; after cycles 2, 4, 6 and 12 of induction treatment (each induction cycle is 28 days); after cycles 6 and 12 of maintenance treatment (each maintenance cycle is 28 days))
- Attainment of ≥VGPR(From the date of Randomisation 1 to the end of 12 cycles of induction treatment (each induction cycle is 28 days))
- Time to next treatment(The time from the date of Randomisation 1 to the start date of the next line of treatment or death from any cause, up to 120 months)
- Time to improved response(The time from the date of Randomisation 2 to the date the response category is first improved, up to 120 months)
- EORTC QLQ-MY20_questionnaire(Randomisation 1; after cycles 2, 4, 6 and 12 of induction treatment (each induction cycle is 28 days); after cycles 6 and 12 of maintenance treatment (each maintenance cycle is 28 days))
- Incidence of treatment-emergent adverse events (Toxicity and safety, including incidence of second malignancies)(Baseline, end of each induction cycle (each induction cycle is 28 days), end of each maintenance cycle (each maintenance cycle is 28 days), until disease progression, up to 120 months)
- EQ-5D-3L_questionnaire(Randomisation 1; after cycles 2, 4, 6 and 12 of induction treatment (each induction cycle is 28 days); after cycles 6 and 12 of maintenance treatment (each maintenance cycle is 28 days))