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

Официальное название

Individualized Dynamic Frailty-tailored Therapy (DynaFiT) in Elderly Patients With Newly Diagnosed Multiple Myeloma: a Prospective and Multi-center Study

Обзор

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.

Подробное описание

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.

Первичные конечные точки

• Overall response rate (at least PR) on induction therapy [Срок оценки: From the date of inclusion to the end of induction therapy, up to 8 months.]

Вторичные конечные точки (5)

• Rate of treatment discontinued(TD) [Срок оценки: The time from the date of inclusion to the date of treatment discontinued from any cause, up to 24 months.]
• Treatment related adverse event(TRAE) [Срок оценки: Baseline, end of every induction cycle and maintenance cycle, until disease progression or treatment discontinued, up to 24 months.]
• Early mortality(EM) [Срок оценки: The time from the date of inclusion to the date of death from any cause, up to 24 months.]
• Progression-free survival(PFS) [Срок оценки: 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.]
• Overall survival (OS) [Срок оценки: The time from the date of inclusion to the date of death from any cause, up to 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

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

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Китай · 1 центр

• The First Hospital of Jilin University — Changchun

Публикации

• Kumar SK, Rajkumar V, Kyle RA, van Duin M, Sonneveld P, Mateos MV, Gay F, Anderson KC. Multiple myeloma. Nat Rev Dis Primers. 2017 Jul 20;3:17046. doi: 10.1038/nrdp.2017.46. PMID 28726797
• Global Burden of Disease Cancer Collaboration; Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, Abdel-Rahman O, Abdelalim A, Abdoli A, Abdollahpour I, Abdulle ASM, Abebe ND, Abraha HN, Abu-Raddad LJ, Abualhasan A, Adedeji IA, Advani SM, Afarideh M, Afshari M, Aghaali M, Agius D, Agrawal S, Ahmadi A, Ahmadian E, Ahmadpour E, Ahmed MB, Akbari ME, Akinyemiju T, Al-Aly Z, AlAbdulKader AM, PMID 31560378
• Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, Kapoor P, Dingli D, Hayman SR, Leung N, Lust J, McCurdy A, Russell SJ, Zeldenrust SR, Kyle RA, Rajkumar SV. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014 May;28(5):1122-8. doi: 10.1038/leu.2013.313. Epub 2013 Oct 25. PMID 24157580
• Cardoso AL, Fernandes A, Aguilar-Pimentel JA, de Angelis MH, Guedes JR, Brito MA, Ortolano S, Pani G, Athanasopoulou S, Gonos ES, Schosserer M, Grillari J, Peterson P, Tuna BG, Dogan S, Meyer A, van Os R, Trendelenburg AU. Towards frailty biomarkers: Candidates from genes and pathways regulated in aging and age-related diseases. Ageing Res Rev. 2018 Nov;47:214-277. doi: 10.1016/j.arr.2018.07.004. PMID 30071357
• Bringhen S, Mateos MV, Zweegman S, Larocca A, Falcone AP, Oriol A, Rossi D, Cavalli M, Wijermans P, Ria R, Offidani M, Lahuerta JJ, Liberati AM, Mina R, Callea V, Schaafsma M, Cerrato C, Marasca R, Franceschini L, Evangelista A, Teruel AI, van der Holt B, Montefusco V, Ciccone G, Boccadoro M, San Miguel J, Sonneveld P, Palumbo A. Age and organ damage correlate with poor survival in myeloma patient PMID 23445873
• Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar SV, Moreau P. Revised International Staging System for PMID 26240224
• Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an Inter PMID 25628469
• Coulson AB, Royle KL, Pawlyn C, Cairns DA, Hockaday A, Bird J, Bowcock S, Kaiser M, de Tute R, Rabin N, Boyd K, Jones J, Parrish C, Gardner H, Meads D, Dawkins B, Olivier C, Henderson R, Best P, Owen R, Jenner M, Kishore B, Drayson M, Jackson G, Cook G. Frailty-adjusted therapy in Transplant Non-Eligible patients with newly diagnosed Multiple Myeloma (FiTNEss (UK-MRA Myeloma XIV Trial)): a study p PMID 35654466

Идентификаторы

NCT: NCT06099912 · DynaFiT

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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