A Study of the Efficacy and Safety of BCD-248 in Combination With Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma (AMMADINA)

Официальное название

A Phase III Open-Label, Randomized Study of the Efficacy and Safety of BCD-248 in Combination With Daratumumab Versus Daratumumab, Pomalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma

Обзор

The aim of the study is to assess the efficacy and safety of the BCD-248 in combination with daratumumab versus the combination of daratumumab, pomalidomide, and dexamethasone in the treatment of relapsed or refractory multiple myeloma. The study will be conducted in a population of male and female subjects aged 18 years and older, with confirmed symptomatic multiple myeloma with measurable disease, who have received one prior line of therapy that included a proteasome inhibitor and lenalidomide and were refractory to lenalidomide, or who have received two or three prior lines of therapy that included a proteasome inhibitor and lenalidomide, with disease progression during or after the last line of therapy.

Вмешательства

• Препарат BCD-248 + daratumumab
  BCD-248 subcutaneously, daratumumab intravenously
• Препарат Daratumumab + pomalidomide + dexamethasone
  Daratumumab intravenously, pomalidomide per os, dexamethasone per os

Первичные конечные точки

• Frequency of MRD negativity by flow cytometry at 12 months from the start of therapy [Срок оценки: up to 12 months]
• Progression-free survival according to the International Myeloma Working Group (IMWG) criteria [Срок оценки: up to 36 months]

Вторичные конечные точки (12)

• Overall response rate (at least partial response) according to the IMWG criteria. [Срок оценки: up to 5 years]
• Frequency of at least a complete response according to the IMWG criteria. [Срок оценки: up to 5 years]
• Frequency of at least a very good partial response according to the IMWG criteria. [Срок оценки: up to 5 years]
• Frequency of MRD negativity. [Срок оценки: up to 5 years]
• Frequency of sustained MRD negativity. [Срок оценки: up to 5 years]
• Time to response. [Срок оценки: up to 5 years]
• Duration of response. [Срок оценки: up to 5 years]
• Time to progression. [Срок оценки: up to 5 years]
• Overall survival. [Срок оценки: up to 5 years]
• Ctrough of BCD-248. [Срок оценки: up to 12 months]
• Changes over time in the concentration of soluble BCMA in the blood. [Срок оценки: up to 12 months]
• Changes over time in lymphocyte populations. [Срок оценки: up to 12 months]

Критерии участия

Критерии включения

• Signed informed consent form.
• Age ≥18 years.
• Documented diagnosis of multiple myeloma according to the IMWG criteria.
• Measurable disease at screening.
• At least 1, but not more than 3 prior lines of antimyeloma therapy, including lenalidomide and a proteasome inhibitor.
• Documented progression according to the IMWG criteria during or after the last line of therapy.
• ECOG score 0-2.
• Resolution of symptoms of toxicity on the prior line of therapy.

Критерии исключения

• Prior therapy with anti-BCMA or anti-CD3 drugs, pomalidomide.
• Refractory to anti-CD38 monoclonal antibodies according to the IMWG criteria.
• Use of any investigational products or medical devices within 28 days prior to randomization or planned use of investigational products or medical devices during participation in this study.
• Hematopoietic stem cell transplantation - prior to randomization or planned during the study
• Plasmapheresis within 14 days prior to randomization.
• Administration of a live attenuated vaccine within 28 days prior to randomization.
• A history of myelodysplastic syndrome or other malignancies other than multiple myeloma within 5 years prior to screening.
• Life-threatening acute complications of the underlying disease.
• Concomitant diseases and/or conditions that significantly increase the risk of AEs during the study:

• Stable angina pectoris, functional class III-IV.
• Unstable angina pectoris and/or myocardial infarction within 6 months prior to randomization.
• Congestive heart failure, NYHA class III-IV.
• Clinically significant (according to the Investigator) cardiac arrhythmia and conduction disorders that do not respond to the maximum possible antiarrhythmic therapy (therapy must be stable for 4 weeks before the planned start of the study therapy).
• Moderate to severe asthma, uncontrolled asthma, asthma with forced expiratory volume in 1 second <50% of predicted normal.
• Chronic obstructive pulmonary disease with forced expiratory volume in 1 second <50% of predicted normal.
• A history of angioneurotic edema, severe respiratory failure.
• Active autoimmune diseases. Patients with type 1 diabetes mellitus and hypothyroidism, requiring only hormone replacement therapy, as well as with skin diseases (vitiligo, alopecia, psoriasis, etc.), which do not require systemic therapy, are allowed to participate.
• Thromboembolic (deep vein thrombosis, pulmonary embolism) or cerebrovascular (stroke, transient ischemic attack) events within 6 months prior to randomization.
• Any infection within 14 days prior to randomization that requires systemic etiological therapy or may, in the Investigator's opinion, increase the risk of infectious complications.
• Any other concomitant disease or condition, which, in the Investigator's opinion, significantly increases the risk of AEs in the study.
• Subjects with amyloidosis, POEMS syndrome, plasma cell leukemia
• CNS involvement or clinical signs of meningeal involvement of multiple myeloma.
• HIV infection, active HBV infection, hepatitis C.
• Hypersensitivity, allergy, or intolerance to monoclonal antibodies or any component of BCD-248, daratumumab, pomalidomide, or dexamethasone.
• Major surgery within less than 14 days prior to the expected start of the study therapy, incomplete recovery from surgery, or planned surgery during participation in the study.
• Pregnancy or breastfeeding, as well as intention to become pregnant or father a child during the study period and within 180 days after receiving the last dose of the IP.

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

Россия · 15 центров

• SBHI "Chelyabinsk regional clinical hospital" — Chelyabinsk
• SBHI "Regional oncological dispensary" — Irkutsk
• SAHI "Republican Clinical Oncology Dispensary of the Ministry of Health of the Republic of — Kazan'
• Regional Government-Owned Publicly Funded Healthcare Institution "Regional Clinical Hospit — Krasnoyarsk
• Branch Office of Hadassah Medical Ltd. — Moscow
• BHI of the Omsk region "Clinical Oncological Dispensary" — Omsk
• St. Petersburg State Healthcare Institution "City Hospital No. 15" — Saint Petersburg
• FSBI "National Medical Research Center named after V.A. Almazov" of the Ministry of Health — Saint Petersburg
• … и ещё 7 центров

Беларусь · 1 центр

• SI "Republican Scientific and Practical Center for Radiation Medicine and Human Ecology" — Homyel

Идентификаторы

NCT: NCT07742215 · BCD-248-3/AMMADINA

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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