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

Официальное название

iFIT (UK-MRA Myeloma XVIII): Immunotherapy Approaches Adapted for Fitness in Newly Diagnosed Transplant Ineligible Patients With Myeloma

Обзор

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.

Вмешательства

• Препарат Daratumumab
  Participants will receive daratumumab by subcutaneous injection. Each cycle is 28 days.
• Препарат Lenalidomide
  Taken orally as capsules. Each cycle is 28 days. Dose can be adjusted for frailty and renal function.
• Препарат Dexamethasone
  Taken as oral tablets, oral solution, or given by IV. Each cycle is 28 days. Dose can be adjusted for frailty and renal function.
• Препарат Teclistamab
  Participants will receive teclistamab by subcutaneous injection. Each cycle is 28 days.
• Препарат Talquetamab
  Participants will receive talquetamab by subcutaneous injection. Each cycle is 28 days.

Первичные конечные точки

• iFIT1: Progression-free survival (PFS) [Срок оценки: From iFIT1 randomisation to PFS event, assessed up to a maximum of 10.5 years post-randomisation.]
• iFIT2: Event-free survival (EFS) [Срок оценки: 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 [Срок оценки: 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.]

Вторичные конечные точки (12)

• Progression-free survival (PFS; iFIT2 only) [Срок оценки: From iFIT2 randomisation to PFS event, assessed up to a maximum of 10.5 years post-randomisation.]
• Time to progression (TTP) [Срок оценки: 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) [Срок оценки: From iFIT1/iFIT2/iFIT3 randomisation to PFS2 event, assessed up to a maximum of 10.5 years post-randomisation.]
• Overall survival (OS) [Срок оценки: 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) [Срок оценки: From iFIT1 randomisation to EFS event, assessed up to a maximum of 6.5 years post-randomisation.]
• Survival after progression [Срок оценки: From disease progression to death, assessed up to a maximum of 10.5 years post-randomisation.]
• Time to next treatment (TTNT) [Срок оценки: From registration to TTNT event, assessed up to a maximum of 10.5 years post-randomisation.]
• Overall response rate (ORR) [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: From iFIT1/iFIT2/iFIT3 randomisation up to a maximum of 6.5 years post-randomisation.]
• Time to improved response [Срок оценки: From iFIT1/iFIT2/iFIT3 randomisation to first recorded improved response, up to a maximum of 6.5 years post-randomisation.]

Критерии участия

Eligibility criteria for registration:

Inclusion criteria for registration:

• 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.

Exclusion criteria for registration:

• 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:

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Великобритания · 5 центров

• Bristol Haematology and Oncology Centre — Bristol
• Eastbourne District General Hospital — Eastbourne
• St James University Hospital — Leeds
• The Clatterbridge Cancer Centre - Liverpool — Liverpool
• The Royal Marsden Hospital — London

Идентификаторы

NCT: NCT07649525 · 1010810

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗