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Personalising Treatment for Myeloma Patients Based on Initial Response to NHS Treatment and Their Overall Fitness Level

ConditionsMultiple Myeloma (MM)Plasma Cell Leukemia (PCL)
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Leeds

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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,

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Daratumumab

    Drug

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

  • Lenalidomide

    Drug

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

  • Dexamethasone

    Drug

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

  • Teclistamab

    Drug

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

  • Talquetamab

    Drug

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

Treatment groups

1,226 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: DRd inductionActive comparator 3 interventions
Group B: iFIT1 - DRd to PDActive comparator 3 interventions
Group C: iFIT1 - Daratumumab plus teclistamab (Dara-Tec)Experimental treatment 2 interventions
Group D: iFIT1 - Daratumumab plus talquetamab (Dara-Tal)Experimental treatment 2 interventions
Group E: iFIT2 - DRd to PDActive comparator 3 interventions
Group F: iFIT2 - DR to PDExperimental treatment 2 interventions
Group G: iFIT3 - DR to PDActive comparator 2 interventions
Group H: iFIT3 - DR for 18 cyclesExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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.

Time frame
From iFIT1 randomisation to PFS event, assessed up to a maximum of 10.5 years post-randomisation.
2

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.

Time frame
From iFIT2 randomisation to EFS event, assessed up to a maximum of 6.5 years post-randomisation.
3

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.

Time frame
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

1

Progression-free survival (PFS; iFIT2 only)

The time from iFIT2 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.

Time frame
From iFIT2 randomisation to PFS event, assessed up to a maximum of 10.5 years post-randomisation.
2

Time to progression (TTP)

The time from iFIT1/iFIT2/iFIT3 randomisation to first documented evidence of disease progression. Participants who died without progression will be censored at their date of death. Participants alive and progression-free at the time of analysis will be censored at their last known date to be alive and progression-free.

Time frame
From iFIT1/iFIT2/iFIT3 randomisation to TTP event, assessed up to a maximum of 10.5 years post-randomisation.
3

Time to second PFS event (PFS2)

The time from iFIT1/iFIT2/iFIT3 randomisation to the second documented evidence of progressive disease or death from any cause. Participants alive and for whom a second progression has not been observed at the time of analysis will be censored at their last known date to be alive and second progression-free.

Time frame
From iFIT1/iFIT2/iFIT3 randomisation to PFS2 event, assessed up to a maximum of 10.5 years post-randomisation.
4

Overall survival (OS)

The time from iFIT1/iFIT2/iFIT3 randomisation to death from any cause. Participants alive at the time of analysis will be censored at their last known date to be alive.

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

Other outcomes

1

Exploratory endpoint - investigation into bone disease and therapy

Observe and understand current UK bone therapy practice and investigate how it impacts on various bone and clinical myeloma outcomes, in order to generate hypotheses to inform future research in this area. This includes bone therapy planned and prescribed, dental assessment received, and bone disease (including SREs) experienced.

Time frame
From registration up to a maximum of 7 years post-registration.
2

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

Certain genetic characteristics and medical history are suspected to influence the incidence and rate of infections. These will be investigated under this endpoint including iVIG usage and vaccination history. The ability to predict prospectively which participants are most at risk of infections could support the implementation of novel immunotherapies in practice. This will also be investigated under this endpoint.

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

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Leeds

Lead sponsor

Cancer Research UK

Collaborator

Blood Cancer UK

Collaborator

Johnson & Johnson

Collaborator

Source ClinicalTrials.gov
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