Use of Elranatamab in Patients With High-risk Smoldering Multiple Myeloma

Официальное название

A Multi-center, Open-label, Phase 2 Study of Elranatamab in Patients With High-risk Smoldering Multiple Myeloma

Обзор

This is a multicenter, single arm, open-label, Phase 2 study in high risk smoldering myeloma patients. The primary objective is to determine the efficacy of Elranatamab in patients with previously untreated high-risk SMM. The key-secondary objective is to determine the safety of Elranatamab in patients with previously untreated high-risk SMM.

Вмешательства

• Препарат Elranatamab
  Elranatamab will be administered via a subcutaneous injection (SC)

Первичные конечные точки

• Complete Remission (CR) rate [Срок оценки: average 24 weeks]

Вторичные конечные точки (9)

• Overall response rate (ORR) [Срок оценки: average 24 weeks]
• MRD-negative CR (MRD_CR) [Срок оценки: average 24 weeks]
• Progression-free survival (PFS) [Срок оценки: time from the date of 1st dose to to the date of disease progression or death, assed up to 4 years after last dose]
• Time to progression (TTP) [Срок оценки: time from the date of 1st dose to progression or death, assed up to 4 years after last dose]
• Progression free survival 2 (PFS2) [Срок оценки: time from the date of 1st dose to progression on the next line of treatment or death,assed up to 4 years after last dose]
• Overall survival (OS) [Срок оценки: time from the date of 1st dose to date of death, assed up to 4 years after last dose]
• Time to response (TTR) [Срок оценки: time frrom the date of 1st dose to the first documented response]
• Change in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module (EORTC QLQ-C30) [Срок оценки: from screening, cycle 1 and every 3 cycles there after up to end of treatment and 28 days after last treatment]
• Change in EORTC QLQ- 20-item Multiple Myeloma module (MY-20) score [Срок оценки: from screening, cycle 1 and every 3 cycles there after up to end of treatment and 28 days after last treatment]

Критерии участия

Критерии включения

• >18 years of age
• Diagnosis of SMM for ≤5 years with measurable disease, defined as serum M protein:

≥1g/dL or urine M protein ≥200 mg/24 hours or involved serum FLC ≥100 mg/Land abnormal serum FLC ratio.

• BMPCs ≥10% and <60%
• Presence of at least 2 high risk factors, including

• Serum M protein ≥2 g/dL,
• BMPC >20%
• Serum involved/uninvolved FLC ratio > 20
• ECOG performance status score of 0 or 1
• Subjects must meet the following laboratory parameters, per laboratory reference range (performed at most 15 days before cycle 1 day 1)

• Absolute neutrophil count ≥1.0 x 109/L (ie, ≥1000/μL)
• Platelet count ≥75 x 109/L
• Aspartate aminotransferase (AST) ≤2.5 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) ≤2.5 x ULN
• Total bilirubin ≤1.5 x ULN, except in subjects with congenital bilirubinemia,such as Gilbert syndrome (in which case direct bilirubin ≤2.0 x ULN is required)
• Subject must sign an informed consent form (ICF) or their legally acceptable representative must sign indicating that he or she understands the purpose of, and procedures required for the study and is willing to participate in the study.
• Women of childbearing potential must have a negative serum or urine pregnancy test at screening and before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (One highly effective method and one additional effective method) used at the same time, and continuing for at least 5 months after the last dose of Elranatamab. Women must also agree to notify pregnancy during the study.

Критерии исключения

• Previous therapy with any systemic therapy for multiple myeloma.
• Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement):

• Increased calcium levels: Corrected serum calcium >1 mg/dL above the ULN or >11 mg/dL
• Renal insufficiency: Determined by glomerular filtration rate (GFR) <40 mL/min/1.73 m² (Modification of Diet in Renal Disease \[MDRD\] Formula) or serum creatinine >2 mg/dL
• Anemia (hemoglobin 2 g/dL below lower limit of normal or <10 g/dL or both) transfusion support or concurrent treatment with erythropoietin stimulating agents is not permitted
• ≥ 1 bone lytic lesion
• BMPCs ≥60%
• Serum involved/uninvolved FLC ratio ≥100 and an involved FLC ≥100mg/L
• Whole body magnetic resonance imaging (WB-MRI) or positron emission tomography-computed tomography (PET-CT) with more than 1 bone focal lesion (≥5 mm in diameter)
• Diagnosis of primary amyloidosis, POEMS syndrome, monoclonal gammopathy of undetermined significance, symptomatic multiple myeloma, or solitary plasmacytoma.
• Subject has a diagnosis of Waldenström's macroglobulinemia, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions.
• Subject has had plasmapheresis within 14 days of elegibility confirmation.
• Myocardial infarction within 6 months prior to enrolment according to NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
• Ongoing Grade 2 or higher peripheral sensory/motor peripheral neuropathy (PN), history of GBS or GBS variants, or history of grade 3 or higher peripheral motor polyneuropathy
• Subject has had major surgery within 2 weeks before elegibility confirmation or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study.
• Clinically relevant active infection or serious co-morbid medical conditions
• Prior malignancy except adequately treated basal cell or squamous cell skin cancer, in situ cervical, breast or prostate cancer free of disease since 5 years.
• Female subject who is pregnant or breast-feeding
• Serious medical or psychiatric illness likely to interfere with participation in study
• Uncontrolled diabetes mellitus
• Known HIV infection; Known active hepatitis B or C viral infection; known active COVID-19/SARS-CoV-2 infection
• Live attenuated vaccine administered within 4 weeks of the first dose of study intervention
• Ongoing treatment with corticosteroids : dose >10mg prednisone etc.
• Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Италия · 12 центров

• AOU Consorziale Policlinico di Bari — Bari
• A.O. Papa Giovanni XXIII — Bergamo
• A.O.U. Careggi — Florence
• A.O.U. Policlinico S. Martino - Ematologia — Genova
• Meldola-Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.) — Meldola
• Ospedale Papardo — Messina
• A.O.U. Maggiore della Carità Novara — Novara
• A.O. di Padova — Padova
• … и ещё 4 центра

Франция · 7 центров

• CHD Vendée — La Roche-sur-Yon
• CHRU de Lille - Hopital Claude Huriez — Lille
• CHU Saint Eloi Département d'Hématologie Clinique — Montpellier
• CHU Hôtel-Dieu, 1, place Alexis Ricordeau, 44093 NANTES Cedex 1, FRANCE — Nantes
• CHU NICE - Hôpital Archet — Nice
• CHU Poitiers - Pôle régional de Cancérologie — Poitiers
• CHRU Hôpital Bretonneau — Tours

Нидерланды · 3 центра

• Maastricht UMC — Maastricht
• St. Antonius Ziekenhuis — Nieuwegein
• Erasmus MC — Rotterdam

Финляндия · 1 центр

• Helsinki University Hospital — Helsinki

Греция · 1 центр

• Alexandra General Hospital -Department of Clinical Therapeutics N.K. Univ. of Athens — Athens

Норвегия · 1 центр

• Oslo Myeloma Center — Oslo

Идентификаторы

NCT: NCT06183489 · EMN34/2023-505775-70-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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