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Contact Information:

Rowena Henderson +44 (0) 113 343 1159
ctru_myelomaxiv@leeds.ac.uk


Anna Hockaday ctru_myelomaxiv@leeds.ac.uk


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Be Part of Research - Trial Details - Myeloma XIV: Frailty-adjusted Therapy in Transplant Non-Eligible Patients With Newly Diagnosed Multiple Myeloma
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Myeloma XIV: Frailty-adjusted Therapy in Transplant Non-Eligible Patients With Newly Diagnosed Multiple Myeloma

Not Recruiting

Open to: ALL

Age: 18.0 - N/A

Bournemouth Newcastle Aberdeen Reading London Manchester Canterbury Bristol Cheltenham Blackpool

Medical Conditions

Multiple Myeloma

This information is provided directly by researchers, and we recognise that it isn't always easy to understand. We are working with researchers to improve the accessibility of this information. In some summaries, you may come across links to external websites. These websites will have more information to help you better understand the study.


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.

Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.  

The recruitment start and end dates are as follows:

Aug 2020 Dec 2024

Publications

"Coulson AB, Royle KL, Pawlyn C, Cairns DA, Hockaday A, Bird J, Bowcock S, Kaiser M, de Tute R, Rabin N, Boyd K, Jones J, Parrish C, Gardner H, Meads D, Dawkins B, Olivier C, Henderson R, Best P, Owen R, Jenner M, Kishore B, Drayson M, Jackson G, Cook G. Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study protocol for a randomised phase III trial. BMJ Open. 2022 Jun 2;12(6):e056147. doi: 10.1136/bmjopen-2021-056147."; "35654466"

INTERVENTIONAL

Intervention Type : DRUG
Intervention Description : In the reactive arm at Randomisation 1, participants will receive IRD induction therapy with standard up-front dosing, with toxicity assessed at each cycle and doses adjusted in accordance with the guidelines given in the trial protocol. All participants will be given the following starting doses:

Ixazomib: 4mg/day on days 1, 8 and 15, taken orally

Lenalidomide: 25mg/day on days 1-21, taken orally

Dexamethasone: 40mg on days 1, 8, 15 and 22 for participants aged ≤75 years, or 20mg on days 1, 8, 15 and 22 for participants aged \> 75 years; taken orally

Participants will receive this dosing regimen for 12 cycles of induction treatment, in the absence of disease progression or unacceptable toxicity. Each cycle is 28 days.

Intervention Arm Group : R1: IRD induction therapy (reactive);

Intervention Type : DRUG
Intervention Description : In the adaptive arm at Randomisation 1, participants will receive IRD induction therapy with up-front dose reductions adjusted according to their frailty score: fit, unfit, or frail. The starting doses for each frailty category are described below:

1. Fit category:

Ixazomib: 4mg/day on days 1, 8 and 15, taken orally Lenalidomide: 25mg on days 1-21, taken orally Dexamethasone: 40mg on days 1, 8, 15 and 22, taken orally2. Unfit category:

Ixazomib: 4mg/day on days 1, 8 and 15, taken orally Lenalidomide: 15mg on days 1-21, taken orally Dexamethasone: 20mg on days 1, 8, 15 and 22, taken orally3. Frail category:

Ixazomib: 4mg/day on days 1, 8 and 15, taken orally Lenalidomide: 10mg on days 1-21, taken orally Dexamethasone: 10mg on days 1, 8, 15 and 22, taken orally

Participants will receive this dosing regimen for 12 cycles of induction treatment, in the absence of disease progression or unacceptable toxicity. Each cycle is 28 days.

Intervention Arm Group : R1: IRD induction therapy (adaptive);

Intervention Type : DRUG
Intervention Description : Participants randomised to receive lenalidomide plus placebo maintenance at Randomisation 2 will receive the following starting doses:

Lenalidomide: 10mg\*/day on days 1-21, taken orally Placebo: 4mg\*/day on days 1, 8 and 15

\* or final dose administered at the end of induction treatment if lower.

This dosing regimen is continued for every maintenance cycle. Participants will continue maintenance treatment until disease progression or intolerance/unacceptable toxicity. Each maintenance cycle is 28 days.

Randomisation 2 is double-blind - participants and their treating clinicians will be blinded to maintenance allocation.

Intervention Arm Group : R2: Lenalidomide plus placebo maintenance;

Intervention Type : DRUG
Intervention Description : Participants randomised to receive lenalidomide plus ixazomib maintenance at Randomisation 2 will receive the following starting doses:

Lenalidomide: 10mg\*/day on days 1-21, taken orally Ixazomib: 4mg\*/day on days 1, 8 and 15

\* or final dose administered at the end of induction treatment if lower.

This dosing regimen is continued for every maintenance cycle. Participants will continue maintenance treatment until disease progression or intolerance/unacceptable toxicity. Each maintenance cycle is 28 days.

Randomisation 2 is double-blind - participants and their treating clinicians will be blinded to maintenance allocation.

Intervention Arm Group : R2: Lenalidomide + ixazomib maintenance;



You can take part if:



You may not be able to take part if:


This is in the inclusion criteria above


Below are the locations for where you can take part in the trial. Please note that not all sites may be open.

  • Royal Bournemouth Hospital
    Bournemouth
  • Freeman Hospital
    Newcastle
  • Aberdeen Royal Infirmary
    Aberdeen
  • Royal Berkshire Hospital
    Reading
  • University College Hospital
    London
  • Manchester Royal Infirmary
    Manchester
  • Kent and Canterbury Hospital
    Canterbury
  • Bristol Haematology and Oncology Centre
    Bristol
  • Cheltenham General Hospital
    Cheltenham
  • Blackpool Victoria Hospital
    Blackpool

Anna Hockaday ctru_myelomaxiv@leeds.ac.uk


Rowena Henderson +44 (0) 113 343 1159
ctru_myelomaxiv@leeds.ac.uk



The study is sponsored by University of Leeds and is in collaboration with Cancer Research UK; Takeda; Celgene.



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Read full details for Trial ID: NCT03720041
Last updated 10 June 2021

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