iFIT (UK-MRA Myeloma XVIII): Immunotherapy Approaches Adapted for Fitness in Newly Diagnosed Transplant Ineligible Patients With Myeloma
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,226
- 试验地点
- 5
- 主要终点
- iFIT1: Progression-free survival (PFS)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
DRd induction
All participants will receive standard of care treatment with daratumumab, lenalidomide, and dexamethasone for an initial 6 cycles.
干预措施: Dexamethasone (Drug)
DRd induction
All participants will receive standard of care treatment with daratumumab, lenalidomide, and dexamethasone for an initial 6 cycles.
干预措施: Daratumumab (Drug)
iFIT1 - DRd to PD
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.
干预措施: Daratumumab (Drug)
iFIT2 - DR to PD
Participants assigned to the iFIT2 pathway and randomised to this arm will continue treatment with daratumumab and lenalidomide until progressive disease.
干预措施: Lenalidomide (Drug)
iFIT2 - DRd to PD
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.
干预措施: Daratumumab (Drug)
iFIT3 - DR to PD
Participants assigned to the iFIT3 pathway and randomised to this arm will continue treatment with daratumumab and lenalidomide until progressive disease.
干预措施: Lenalidomide (Drug)
iFIT3 - DR for 18 cycles
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.
干预措施: Daratumumab (Drug)
iFIT1 - DRd to PD
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.
干预措施: Lenalidomide (Drug)
iFIT1 - Daratumumab plus teclistamab (Dara-Tec)
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.
干预措施: Daratumumab (Drug)
iFIT1 - Daratumumab plus teclistamab (Dara-Tec)
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.
干预措施: Teclistamab (Drug)
DRd induction
All participants will receive standard of care treatment with daratumumab, lenalidomide, and dexamethasone for an initial 6 cycles.
干预措施: Lenalidomide (Drug)
iFIT1 - DRd to PD
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.
干预措施: Dexamethasone (Drug)
iFIT1 - Daratumumab plus talquetamab (Dara-Tal)
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.
干预措施: Daratumumab (Drug)
iFIT1 - Daratumumab plus talquetamab (Dara-Tal)
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.
干预措施: Talquetamab (Drug)
iFIT2 - DRd to PD
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.
干预措施: Lenalidomide (Drug)
iFIT2 - DRd to PD
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.
干预措施: Dexamethasone (Drug)
iFIT2 - DR to PD
Participants assigned to the iFIT2 pathway and randomised to this arm will continue treatment with daratumumab and lenalidomide until progressive disease.
干预措施: Daratumumab (Drug)
iFIT3 - DR to PD
Participants assigned to the iFIT3 pathway and randomised to this arm will continue treatment with daratumumab and lenalidomide until progressive disease.
干预措施: Daratumumab (Drug)
iFIT3 - DR for 18 cycles
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.
干预措施: Lenalidomide (Drug)
结局指标
主要结局
iFIT1: Progression-free survival (PFS)
时间窗: From iFIT1 randomisation to PFS event, assessed up to a maximum of 10.5 years post-randomisation.
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.
iFIT2: Event-free survival (EFS)
时间窗: From iFIT2 randomisation to EFS event, assessed up to a maximum of 6.5 years post-randomisation.
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.
iFIT3: Progression-free survival (PFS) and participant-reported overall health and quality of life (QoL) - co-primary outcomes
时间窗: 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.
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.
次要结局
- 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.)
- Maximum response(From iFIT1/iFIT2/iFIT3 randomisation up to a maximum of 6.5 years post-randomisation.)
- Survival after progression(From disease progression to death, assessed up to a maximum of 10.5 years post-randomisation.)
- Time to next treatment (TTNT)(From registration to TTNT event, assessed up to a maximum of 10.5 years post-randomisation.)
- Overall response rate (ORR)(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(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(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.)
- Time to improved response(From iFIT1/iFIT2/iFIT3 randomisation to first recorded improved response, up to a maximum of 6.5 years post-randomisation.)
- Treatment compliance(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(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(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 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 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 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 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.)