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

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.

Eligibility

Eligibility criteria for registration:

Inclusion criteria for registration:

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

Exclusion criteria for registration:

1. Smouldering myeloma (SMM), primary amyloidosis, solitary plasmacytoma of bone or extramedullary plasmacytoma (without additional evidence of myeloma),
2. 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,
3. Previous treatment for myeloma, except as specified in the protocol,
4. Active systemic viral, fungal or bacterial infection requiring systemic therapy. Criteria for specific chronic infections clarified in the protocol, or
5. 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:

Inclusion criteria for randomisation into all iFIT1/iFIT2/iFIT3 pathways:

* 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.

Inclusion criteria specific to randomisation pathways:

* 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),
* Categorised as FRAIL according to the IMWG frailty index (iFIT2), and
* Meet the blood criteria specified in the protocol within 14 days before randomisation (haematological and biochemical) (iFIT1).

Exclusion criteria for randomisation into all iFIT1/iFIT2/iFIT3 pathways:

* Received systemic anti-myeloma therapy other than DRd prior to randomisation. Steroids given (by any route) for reasons other than myeloma disease control are allowed,
* Received a stem cell transplant,
* Participation in any other interventional study for myeloma that involves an IMP during treatment and active monitoring, and
* Pregnant, breast feeding, plans to become pregnant, or plans to father a child whilst enrolled in the study or within a specified period after the last dose.

Exclusion criteria specific to randomisation pathways:

* Stable disease (SD) or progressive disease (PD) as per IMWG response criteria (iFIT1 and iFIT2),
* Partial response (PR), stable disease (SD) or progressive disease (PD) as per IMWG response criteria (iFIT3), and
* Further exclusion criteria related to safety of interventions (iFIT1).

Full inclusion and exclusion criteria are listed in the protocol.

Conditions3

Interventions5

Related trials

• A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03) — Nanjing IASO Biotechnology Co., Ltd.
• A Study of GR1803 Injection Versus Daratumumab, Pomalidomide, and Dexamethasone (DPd) in Participants With Relapsed or Refractory Multiple Myeloma — Genrix (Shanghai) Biopharmaceutical Co., Ltd.
• A Study of JNJ-79635322 in Combination With Daratumumab With or Without Lenalidomide or in Combination With Pomalidomide for Multiple Myeloma — Janssen Research & Development, LLC
• A Study to Learn How Safe and How Well Linvoseltamab Works Compared to Standard Treatment in Adult Patients With Multiple Myeloma Who Are Not Eligible for Transplant — European Myeloma Network B.V.
• Bispecific T-cell Redirectors as Part of First Line Treatment in Transplant Eligible Multiple Myeloma Patients — North Estonia Medical Centre
• Fixed Duration vs Continuous Anti-CD38 Antibody Therapy Among Transplant Ineligible Older Adults With Newly-Diagnosed Multiple Myeloma — Canadian Cancer Trials Group
• GMMG-HD10 / DSMM-XX / 64007957MMY2003, MajesTEC-5 — University of Heidelberg Medical Center
• Optimize First-line Treatment for AL Amyloidosis With t (11; 14) — Jin Lu, MD

Browse More Trials