Individualized Dynamic Frailty-tailored Therapy (DynaFiT) in Elderly Patients With NDMM

Recruiting

• Conditions: Multiple Myeloma; Frailty

• Registration Number: NCT06099912
• Lead Sponsor: FengYan Jin

Brief Summary

Frailty is dynamic and confers poor outcomes in elderly patients with newly diagnosed multiple myeloma (NDMM), mainly because of the high prevalence of treatment discontinuation due to intolerability. We designed a multi-center prospective study (DynaFiT) based on our real-life practice to evaluate the feasibility and benefits of a dynamic frailty-tailored therapy in elderly patients with different fitness/frailty statuses.

Since Dara-based treatment have recently become the new standard regimens, in this amendment of the study, daratumumab added to VRd is recommended as induction therapy regimen.

Detailed Description

Older patients with MM represent a heterogeneous population with different fitness/frailty statuses. Unlike fit patients who can benefit from intensive therapies due to their endurance, frail patients are often susceptible to treatment-related toxicity, leading to treatment discontinuation and poor outcomes. More importantly, frailty can diminish the prognostic impact of disease-related factors over disease trajectory. Thus, it is of utmost importance to determine the fitness/frailty status for treatment decision-making that carefully balances efficacy and safety in this vulnerable population. However, geriatric assessment is often conducted at diagnosis in clinical practice. Although baseline frailty status, as a static risk factor, is significantly associated with OS, its predictive ability decreases over time. Of note, emerging evidence indicates that the fitness/frailty status is highly dynamic because of age increase, disease trajectory, and treatment, raising the notion that frailty-tailored therapy should be designed based on the baseline fitness/frailty status and also according to its longitudinal changes during the treatment course. Thus, current frailty status better predicts OS.

To improve outcomes in elderly patients, this study was designed to investigate an entirely novel therapeutic strategy, the dynamic frailty-tailored therapy, in elderly MM patients with different fitness/frailty statuses.

Study Timeline

• Study Start: 2021-09-08
• Study First Submitted: 2023-10-16
• Study First Submitted QC: 2023-10-19
• Study First Posted: 2023-10-25
• Status Verified: 2024-06
• Last Update Submitted: 2024-07-10
• Last Update Posted: 2024-07-11
• Primary Completion: 2026-09-08
• Study Completion: 2029-09-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• Adult males and females aged ≥65 years who were either transplant-ineligible or had no intent for immediate transplant;
• Subject must have documented multiple myeloma as defined by the criteria below:

Monoclonal plasma cells in the bone marrow 10% or presence of a biopsy-proven plasmacytoma;

Measurable disease as defined by any of the following:

• Serum monoclonal paraprotein (M-protein) level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or

• IgA multiple myeloma: serum M-protein level ≥0.5 g/dL or urine M-protein level ≥200 mg/24 hours; or

• Light chain multiple myeloma: Serum immunoglobulin free light chain ≥10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio.

  • Has not had prior systemic therapy for multiple myeloma;
  • The functional reserve of the organs can withstand systemic therapy;
  • Each subject (or their legally acceptable representative) must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and are willing to participate in the study. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as referenced in the ICF.

Exclusion Criteria

• There are active systemic viral, fungal, or bacterial infections that require systemic anti-infective treatment;
• Severe organ dysfunction (New York Heart Association class III and IV or transaminases ≥5 normal level, except those caused by cardiac and hepatic amyloidosis secondary to MM)
• Patients with prior history of hematologic or solid tumors treated with radiotherapy or chemotherapy(except ≥5 years);
• Patients who currently have hematologic tumors or solid tumors that require radiotherapy or chemotherapy;
• Non-signation of informed consent.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	The time from the date of inclusion to the date of death from any cause, up to 24 months	In each case it is the time from inclusion to the time of death from any cause. Individuals who are lost to follow-up or still alive at the time of analysis will be censored at their last known date to be alive.

Secondary Outcome Measures

Name	Time	Method
Progression-free survival(PFS)	The time from the date of inclusion to the date of first documented evidence of disease progression or death from any cause, up to 24 months.	Progression-free survival(PFS) is defined as the time from inclusion to the time of first documented evidence of disease progression or death from any cause. Individuals who are lost to follow-up or progression-free at the time of analysis will be censored at their last known date to be alive and progression-free. Disease progression is defined according to the IMWG Uniform Response Criteria for Multiple Myeloma.
Rate of treatment discontinued(TD)	The time from the date of inclusion to the date of treatment discontinued from any cause, up to 24 months.	The effect of intensive or mild treatment based on dynamic frailty status on treatment discontinued(TD) in elderly newly diagnosed multiple myeloma.
Treatment related adverse event(TRAE)	Baseline, end of every induction cycle and maintenance cycle, until disease progression or treatment discontinued, up to 24 months.	Toxicity and safety will be reported based on the adverse events, as graded by CTCAE V5 and determined by routine clinical assessments.
Early mortality(EM)	The time from the date of inclusion to the date of death from any cause, up to 24 months.	Early mortality is defined as death within 3, 6, 12 and 24 months (EM3,EM6,EM12 and EM24).
Overall response rate (ORR)	From the date of inclusion to the date of last follow-up, up to 24 months.	Overall response rate is defined as the percentage of participants with presence of stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). ORR assessment will be based on International Myeloma Working Group (IMWG) response criteria.

Trial Locations

Locations (1)

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China