Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Cancer Research UK | OTHER |
| Blood Cancer UK | UNKNOWN |
| Johnson & Johnson | INDUSTRY |
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DRd induction | Active Comparator | All participants will receive standard of care treatment with daratumumab, lenalidomide, and dexamethasone for an initial 6 cycles. |
|
| 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. |
|
| 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. |
|
| 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. |
|
| iFIT2 - DRd to PD |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Daratumumab | Drug | Participants will receive daratumumab by subcutaneous injection. Each cycle is 28 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From iFIT2 randomisation to PFS event, assessed up to a maximum of 10.5 years post-randomisation. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From registration up to a maximum of 7 years post-registration. |
Eligibility criteria for registration:
Inclusion criteria for registration:
Exclusion criteria for registration:
Additional eligibility criteria for randomisation into iFIT1/iFIT2/iFIT3 pathways, as follows:
Inclusion criteria for randomisation into all iFIT1/iFIT2/iFIT3 pathways:
Inclusion criteria specific to randomisation pathways:
Exclusion criteria for randomisation into all iFIT1/iFIT2/iFIT3 pathways:
Exclusion criteria specific to randomisation pathways:
Full inclusion and exclusion criteria are listed in the protocol.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Emma McNaught | Contact | 0113 343 1978 | ctru-ifit@leeds.ac.uk | |
| Catherine Olivier | Contact | ctru-ifit@leeds.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Gordon Cook | Leeds Institute of Clinical Trials Research | Study Chair |
| Charlotte Pawlyn | Institute of Cancer Research, United Kingdom | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bristol Haematology and Oncology Centre | Bristol | BS2 8ED | United Kingdom |
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.
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.
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.
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 17, 2025 | Feb 3, 2026 |
Not provided
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
Not provided
Not provided
Not provided
Not provided
| 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. |
|
| 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. |
|
| 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. |
|
| 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. |
|
|
| 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. |
|
|
| 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. | 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) | 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. | From iFIT1/iFIT2/iFIT3 randomisation to PFS2 event, assessed up to a maximum of 10.5 years post-randomisation. |
| 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. | 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) | The time from iFIT1 randomisation to the first of the following events: grade 4 haematological AEs (anaemia, neutropenia, thrombocytopenia), 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 iFIT1 randomisation to EFS event, assessed up to a maximum of 6.5 years post-randomisation. |
| Survival after progression | The time from first documented evidence of disease progression to death from any cause. Participants alive at the time of analysis will be censored at their last known date to be alive. This endpoint is only defined for those who experience progression. | From disease progression to death, assessed up to a maximum of 10.5 years post-randomisation. |
| Time to next treatment (TTNT) | The time from registration to the date of commencement of next treatment. Participants who do not receive next line treatment will be censored at the date of the last assessment or follow-up visit where they are known to have received no new therapy. | From registration to TTNT event, assessed up to a maximum of 10.5 years post-randomisation. |
| Overall response rate (ORR) | Overall response rate using the disease response category (sCR, CR, VGPR, PR, MR, SD, or PD). | Measured after 6 28-day cycles of standard of care induction DRd treatment, and further timepoints up to approximately 30 months post-iFIT1/iFIT2/iFIT3 randomisation, dependent on treatment pathway. |
| Attainment of ≥VGPR | Attainment of ≥VGPR using the binary disease response category (≥VGPR: sCR, CR, VGPR vs. \ | Measured after 6 28-day cycles of standard of care induction DRd treatment, and further timepoints up to approximately 30 months post-iFIT1/iFIT2/iFIT3 randomisation, dependent on treatment pathway. |
| Attainment of MRD negativity | Attainment of MRD negativity using the binary MRD status category (negative vs. positive) measured using flow cytometry. MRD negativity is defined as at least a serological VGPR and MRD negative bone marrow aspirate at the 10^-5 threshold. | Measured after 6 28-day cycles of standard of care induction DRd treatment, and further timepoints up to approximately 30 months post-iFIT1/iFIT2/iFIT3 randomisation, dependent on treatment pathway. |
| Maximum response | The maximum response attained. | From iFIT1/iFIT2/iFIT3 randomisation up to a maximum of 6.5 years post-randomisation. |
| Time to improved response | The time from iFIT1/iFIT2/iFIT3 randomisation to first recorded improved response, where the baseline response is that recorded at the start of randomised treatment (iFIT1/iFIT2/iFIT3 cycle 1, day 1). Participants whose disease progresses or who die before an improved response is recorded will be censored at the time of progression or death, respectively. Participants alive with no improved response recorded at the time of analysis will be censored at their last known date to be alive. | From iFIT1/iFIT2/iFIT3 randomisation to first recorded improved response, up to a maximum of 6.5 years post-randomisation. |
| Treatment compliance | Treatment compliance including whether all cycles of treatment were completed, the number of cycles completed, the total dose of each trial medication received, the number and causes of dose omissions, dose delays, and dose reductions. | From registration to the end of trial treatment, up to a maximum of 7 years post-registration. |
| Toxicity and safety as graded by NCI-CTCAE v5 | Toxicity and safety based on the adverse events reported as graded by NCI-CTCAE v5. Pregnancies will also be reported. | From registration up to a maximum of 11 years post-registration. SAEs may be reported up to 60 days post-last dose of protocol treatment/cycle of active monitoring. |
| Incidence of secondary primary malignancies | The number and details of all other cancers, defined as secondary primary malignancies. | Measured during standard of care induction DRd treatment and following iFIT1/ iFIT2/iFIT3 randomisation, up to a maximum of 11 years post-registration. |
| Incidence, rate, and type of infections as graded by NCI-CTCAE v5 | Measured using the proportion of participants experiencing an infection of any type or grade as graded by NCI-CTCAE v5. | Measured during standard of care induction DRd treatment and following iFIT1/iFIT2/iFIT3 randomisation, up to a maximum of 7 years post-registration. |
| Quality of life using questionnaires | Measured using the EQ-5D-5L, EORTC QLQ-C30, EORTC QLQ-IL413 questionnaires. This will also be measured using the EORTC QLQ IL414 questionnaire and the Scale of Subjective Total Taste Acuity (STTA) at specified timepoints only. | Measured at the start of cycle 1 and after 6 28-day cycles of DRd induction, and timepoints up to 30 months post-randomisation. The IL414 is measured at the induction timepoints and in iFIT1, and the STTA after 6 28-day cycles of induction and in iFIT1. |
| Objective measures of function | Measured using the 4 metre walk test and mini-cog assessments. | Measured at the start of cycle 1, after 3 28-day cycles, and after 6 28-day cycles of standard of care induction DRd. |
| Cost-utility | Measured using costs, QALYs and net health benefit (QALYs below £20,000). | Measured at the start of cycle 1 of DRd induction, after 6 28-day cycles of DRd induction, and further timepoints up to 30 months post-iFIT1/iFIT2/iFIT3 randomisation. |
| 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. | From iFIT1 randomisation up to a maximum of 6.5 years post-randomisation. |
| Eastbourne District General Hospital | Eastbourne | BN21 2UD | United Kingdom |
|
| St James University Hospital | Leeds | LS9 7TF | United Kingdom |
|
| The Royal Marsden Hospital | London | SM2 5PT | United Kingdom |
|
| Prot_000.pdf |
| ID | Term |
|---|---|
| D009101 | Multiple Myeloma |
| D007952 | Leukemia, Plasma Cell |
| D054219 | Neoplasms, Plasma Cell |
| D000073496 | Frailty |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010265 | Paraproteinemias |
| D001796 | Blood Protein Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D006474 | Hemorrhagic Disorders |
| D008232 | Lymphoproliferative Disorders |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D007938 | Leukemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C556306 | daratumumab |
| C007792 | Fumigant 93 |
| C116560 | darlin protein, Dictyostelium |
| D000077269 | Lenalidomide |
| D003907 | Dexamethasone |
| D051416 | Focal Adhesion Protein-Tyrosine Kinases |
| C000730985 | talquetamab |
| ID | Term |
|---|---|
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D013259 | Steroids, Fluorinated |
| D011505 | Protein-Tyrosine Kinases |
| D011494 | Protein Kinases |
| D017853 | Phosphotransferases (Alcohol Group Acceptor) |
| D010770 | Phosphotransferases |
| D014166 | Transferases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D047908 | Intracellular Signaling Peptides and Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided