NCT07649525

Brief Summary

iFIT is a trial for newly diagnosed transplant-ineligible patients with the bone marrow cancer myeloma. These patients are generally older and have a lower level of fitness than others. Patients can take part if their doctor would otherwise recommend the standard NHS treatment daratumumab, lenalidomide and dexamethasone (DRd). After six months of DRd, the subsequent treatment a patient receives in iFIT is based on two factors: the patient's fitness level and treatment response. The trial compares different treatment strategies to determine whether outcomes can be improved for specific patient groups.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,226

participants targeted

Target at P75+ for phase_3

Timeline
132mo left

Started Jul 2026

Longer than P75 for phase_3

Geographic Reach
1 country

5 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress1%
Jul 2026Jun 2037

First Submitted

Initial submission to the registry

June 2, 2026

Completed
14 days until next milestone

First Posted

Study publicly available on registry

June 16, 2026

Completed
15 days until next milestone

Study Start

First participant enrolled

July 1, 2026

Completed
6.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2033

Expected
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2037

Last Updated

July 15, 2026

Status Verified

July 1, 2026

Enrollment Period

6.9 years

First QC Date

June 2, 2026

Last Update Submit

July 14, 2026

Conditions

Keywords

MyelomaPlatform adaptive designImmunotherapyFrailtyPersonalised therapyBiomarker-driven

Outcome Measures

Primary Outcomes (3)

  • iFIT1: Progression-free survival (PFS)

    The time from iFIT1 randomisation to progression or death from any cause. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free.

    From iFIT1 randomisation to PFS event, assessed up to a maximum of 10.5 years post-randomisation.

  • iFIT2: Event-free survival (EFS)

    The time from iFIT2 randomisation to the first of the following events: grade 4 haematological AEs, grade 3 and 4 non-haematological AEs (including SPMs), discontinuation of trial treatment, progression or death. Participants event-free at the time of analysis will be censored at their last date known to be alive and event-free.

    From iFIT2 randomisation to EFS event, assessed up to a maximum of 6.5 years post-randomisation.

  • iFIT3: Progression-free survival (PFS) and participant-reported overall health and quality of life (QoL) - co-primary outcomes

    PFS: The time from iFIT3 randomisation to progression or death from any cause. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. QoL: The GHS/QoL scale score of the EORTC QLQ-C30 questionnaire. The QoL primary endpoint is measured at 30 months (2.5 years) after iFIT3 randomisation.

    PFS: from iFIT3 randomisation to PFS event, assessed up to a maximum of 10.5 years post-randomisation. QoL: measured at the start of cycle 1 and after 6 28-day cycles of DRd induction, and further timepoints up to 30 months post-iFIT3 randomisation.

Secondary Outcomes (19)

  • Progression-free survival (PFS; iFIT2 only)

    From iFIT2 randomisation to PFS event, assessed up to a maximum of 10.5 years post-randomisation.

  • Time to progression (TTP)

    From iFIT1/iFIT2/iFIT3 randomisation to TTP event, assessed up to a maximum of 10.5 years post-randomisation.

  • Time to second PFS event (PFS2)

    From iFIT1/iFIT2/iFIT3 randomisation to PFS2 event, assessed up to a maximum of 10.5 years post-randomisation.

  • Overall survival (OS)

    From iFIT1/iFIT2/iFIT3 randomisation to OS event, assessed up to a maximum of 10.5 years post-randomisation.

  • Event-free survival (EFS; iFIT1 only)

    From iFIT1 randomisation to EFS event, assessed up to a maximum of 6.5 years post-randomisation.

  • +14 more secondary outcomes

Other Outcomes (2)

  • Exploratory endpoint - investigation into bone disease and therapy

    From registration up to a maximum of 7 years post-registration.

  • Exploratory endpoint - infection interactions and infection risk (iFIT1 only)

    From iFIT1 randomisation up to a maximum of 6.5 years post-randomisation.

Study Arms (8)

DRd induction

ACTIVE COMPARATOR

All participants will receive standard of care treatment with daratumumab, lenalidomide, and dexamethasone for an initial 6 cycles.

Drug: DaratumumabDrug: LenalidomideDrug: Dexamethasone

iFIT1 - DRd to PD

ACTIVE COMPARATOR

Participants assigned to the iFIT1 pathway and randomised to this arm will continue standard of care treatment with daratumumab, lenalidomide, and dexamethasone until progressive disease. Dexamethasone may be stopped due to toxicity.

Drug: DaratumumabDrug: LenalidomideDrug: Dexamethasone

iFIT1 - Daratumumab plus teclistamab (Dara-Tec)

EXPERIMENTAL

Participants assigned to the iFIT1 pathway and randomised to this arm will receive treatment with daratumumab and teclistamab for a fixed duration and then be actively monitored until progressive disease.

Drug: DaratumumabDrug: Teclistamab

iFIT1 - Daratumumab plus talquetamab (Dara-Tal)

EXPERIMENTAL

Participants assigned to the iFIT1 pathway and randomised to this arm will receive treatment with daratumumab and talquetamab for a fixed duration and then be actively monitored until progressive disease.

Drug: DaratumumabDrug: Talquetamab

iFIT2 - DRd to PD

ACTIVE COMPARATOR

Participants assigned to the iFIT2 pathway and randomised to this arm will continue standard of care treatment with daratumumab, lenalidomide, and dexamethasone until progressive disease.

Drug: DaratumumabDrug: LenalidomideDrug: Dexamethasone

iFIT2 - DR to PD

EXPERIMENTAL

Participants assigned to the iFIT2 pathway and randomised to this arm will continue treatment with daratumumab and lenalidomide until progressive disease.

Drug: DaratumumabDrug: Lenalidomide

iFIT3 - DR to PD

ACTIVE COMPARATOR

Participants assigned to the iFIT3 pathway and randomised to this arm will continue treatment with daratumumab and lenalidomide until progressive disease.

Drug: DaratumumabDrug: Lenalidomide

iFIT3 - DR for 18 cycles

EXPERIMENTAL

Participants assigned to the iFIT3 pathway and randomised to this arm will continue treatment with daratumumab and lenalidomide for 18 cycles, and then be actively monitored until progressive disease.

Drug: DaratumumabDrug: Lenalidomide

Interventions

Participants will receive daratumumab by subcutaneous injection. Each cycle is 28 days.

Also known as: D, Dara
DRd inductioniFIT1 - DRd to PDiFIT1 - Daratumumab plus talquetamab (Dara-Tal)iFIT1 - Daratumumab plus teclistamab (Dara-Tec)iFIT2 - DR to PDiFIT2 - DRd to PDiFIT3 - DR for 18 cyclesiFIT3 - DR to PD

Taken orally as capsules. Each cycle is 28 days. Dose can be adjusted for frailty and renal function.

Also known as: R, Revlimid
DRd inductioniFIT1 - DRd to PDiFIT2 - DR to PDiFIT2 - DRd to PDiFIT3 - DR for 18 cyclesiFIT3 - DR to PD

Taken as oral tablets, oral solution, or given by IV. Each cycle is 28 days. Dose can be adjusted for frailty and renal function.

Also known as: d
DRd inductioniFIT1 - DRd to PDiFIT2 - DRd to PD

Participants will receive teclistamab by subcutaneous injection. Each cycle is 28 days.

Also known as: Tec
iFIT1 - Daratumumab plus teclistamab (Dara-Tec)

Participants will receive talquetamab by subcutaneous injection. Each cycle is 28 days.

Also known as: Tal
iFIT1 - Daratumumab plus talquetamab (Dara-Tal)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Newly diagnosed as having symptomatic MM, plasma cell leukaemia or non-secretory MM according to IMWG diagnostic criteria 2014.
  • Considered not suitable to receive autologous stem cell transplant as part of their first line therapy by the treating clinician,
  • Planned for treatment with Daratumumab, Lenalidomide and dexamethasone (DRd) as first line therapy as standard of care,
  • Aged 18 years or greater,
  • Able to provide full informed consent, and
  • Prepared to comply with pregnancy prevention plan.

You may not qualify if:

  • Smouldering myeloma (SMM), primary amyloidosis, solitary plasmacytoma of bone or extramedullary plasmacytoma (without additional evidence of myeloma),
  • Pregnant, breastfeeding, plans to become pregnant, or plans to father a child whilst enrolled in the study or within 3 months after the last dose,
  • Previous treatment for myeloma, except as specified in the protocol,
  • Active systemic viral, fungal or bacterial infection requiring systemic therapy. Criteria for specific chronic infections clarified in the protocol, or
  • Participation in any other interventional study for myeloma that involves an IMP during treatment and active monitoring.
  • Additional eligibility criteria for randomisation into iFIT1/iFIT2/iFIT3 pathways, as follows:
  • Completed 6 cycles of DRd induction therapy after registering within the iFIT study,
  • Able to provide full informed consent, and
  • Prepared to comply with pregnancy prevention plan.
  • Dexamethasone may have been stopped due to toxicity and the participant will remain eligible (iFIT1 and iFIT3),
  • Planned to continue on at least daratumumab (monthly) and lenalidomide (at any dose level) (iFIT1 and iFIT3),
  • Planned to continue on all three DRd medications (dose reductions are allowed) (iFIT2),
  • Achieved a partial response (PR) biochemically (irrespective of MRD status) or achieved a ≥VGPR and are MRD positive, as confirmed by HMDS (central laboratory) (iFIT1 and iFIT2),
  • Achieved a ≥VGPR and are MRD negative, as confirmed by HMDS (central laboratory) (iFIT3),
  • Categorised as FIT or UNFIT according to the IMWG frailty index (iFIT1),
  • +8 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

NOT YET RECRUITING

Eastbourne District General Hospital

Eastbourne, BN21 2UD, United Kingdom

NOT YET RECRUITING

St James University Hospital

Leeds, LS9 7TF, United Kingdom

NOT YET RECRUITING

The Clatterbridge Cancer Centre - Liverpool

Liverpool, L7 8YA, United Kingdom

RECRUITING

The Royal Marsden Hospital

London, SM2 5PT, United Kingdom

NOT YET RECRUITING

MeSH Terms

Conditions

Multiple MyelomaLeukemia, Plasma CellNeoplasms, Plasma CellFrailty

Interventions

daratumumabFumigant 93darlin protein, DictyosteliumLenalidomideDexamethasoneFocal Adhesion Protein-Tyrosine Kinasestalquetamab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System DiseasesLeukemiaPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

PhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingPregnadienetriolsPregnadienesPregnanesSteroidsFused-Ring CompoundsPolycyclic CompoundsSteroids, FluorinatedProtein-Tyrosine KinasesProtein KinasesPhosphotransferases (Alcohol Group Acceptor)PhosphotransferasesTransferasesEnzymesEnzymes and CoenzymesIntracellular Signaling Peptides and ProteinsProteinsAmino Acids, Peptides, and Proteins

Study Officials

  • Gordon Cook

    Leeds Institute of Clinical Trials Research

    STUDY CHAIR
  • Charlotte Pawlyn

    Institute of Cancer Research, United Kingdom

    STUDY CHAIR

Central Study Contacts

Catherine Olivier

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: iFIT is a multi-centre, open-label, phase III platform trial with three randomised-controlled parallel-group components of transplant non-eligible (TNE) patients with newly diagnosed multiple myeloma
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 2, 2026

First Posted

June 16, 2026

Study Start

July 1, 2026

Primary Completion (Estimated)

June 1, 2033

Study Completion (Estimated)

June 1, 2037

Last Updated

July 15, 2026

Record last verified: 2026-07

Data Sharing

IPD Sharing
Will share

De-identified individual participant data datasets generated and/or analysed during the current study will be available upon request from the Clinical Trials Research Unit, University of Leeds (contact CTRU-DataAccess@leeds.ac.uk in the first instance). The conditions of release for aggregate data may differ from those applying to individual participant data. Requests for aggregate data should also be sent to the above email address to discuss and agree suitable requirements for release.

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Data will be made available at the end of the trial, i.e. usually when all primary and secondary endpoints have been met and all key analyses are complete. Data will remain available from then on for as long as CTRU retains the data.
Access Criteria
Data will be released for legitimate secondary research purposes, where the Chief Investigators, Sponsor and CTRU agree that the proposed use has scientific value and will be carried out to a high standard (scientific rigour and information governance and security), and that suitable resources are available. Data will be released in line with participants' consent, all applicable laws relating to data protection and confidentiality, and any contractual obligations to which the CTRU is subject. No IPD will be released before an appropriate agreement is in place governing data retention, usually stipulating that data recipients must delete their copy of the data at the end of the project. The CTRU believes it is best practice for researchers who generated datasets to be involved in subsequent uses of those datasets. Recipients of trial data for secondary research will also receive data dictionaries, key trial documents and any other information required to reuse the datasets.

Locations