Myeloma XIV: Frailty-adjusted Therapy in Transplant Non-Eligible Patients With Newly Diagnosed Multiple Myeloma
Status:
Recruiting
Trial end date:
2024-12-01
Target enrollment:
Participant gender:
Summary
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.