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

Official title

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

Overview

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.

Interventions

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

Primary outcome measures

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

Secondary outcome measures (12)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Russia · 15 centers

• 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
• … and 7 more centers

Belarus · 1 center

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

Identifiers

NCT: NCT07742215 · BCD-248-3/AMMADINA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗