Health Condition 1: C900- Multiple myeloma
Conditions
Interventions
Intervention1: BCD-264: Blinded treatment period: BCD-264 IV once weekly for the first
2 therapy cycles, then once every 2 weeks for 16 weeks (Cycle 3 â?? Cycle 6).
Open-label treatment period: BCD-26
Sponsors
JSC BIOCAD, Russia
Eligibility
Inclusion criteria
Inclusion criteria: Subjects meeting all of the inclusion criteria may participate in this study: 1.Signed informed consent form to participate in the study and the subject s ability to comply with the requirements of the clinical study protocol. 2.Age greater than or equal to 18 years at the time of signing of the informed consent form. 3.Documented diagnosis of multiple myeloma according to IMWG criteria (Appendix 1). Subject s medical history data may be used to demonstrate his/her eligibility according to this inclusion criterion. 4.Measurable disease at screening: (1) M-protein in serum greater than or equal to 1.0 g/dL (10 g/L) or in 24-hour urine greater than or equal to 200 mg; or (2) light chain myeloma: serum involved FLC level greater than or equal to 10 mg/dL (100 mg/L) and abnormal kappa/lambda FLC ratio1. 5.Evidence of at least a partial response (PR) according to IMWG criteria (as assessed by the Investigator) to at least 1 prior line of therapy. 6.Subjects with relapsed and/or refractory multiple myeloma who previously received therapy with proteasome inhibitors and immunomodulatory drugs, and who had disease progression during or after the last line of therapy: (1) Relapsing myeloma: initial response to previous treatment, followed by confirmed progressive disease (PD) according to IMWG criteria more than 60 days after cessation of treatment; (2) refractory myeloma: less than 25 % reduction of M-protein or confirmed progressive disease (PD) according to IMWG criteria during the previous line of therapy or 60 days or less after cessation of treatment. 7.ECOG score 0 2. 8.Laboratory values at screening: (1) absolute neutrophil count greater than or equal to 1000/ L (1.0 109/L); the use of G-CSF is allowed; (2) platelets greater than or equal to 30,000/ L (30 109/L) without transfusions within 7 days prior to laboratory testing; (3) hemoglobin greater than or equal to 7.5 g/dL (greater than or equal to 75 g/L) or greater than or equal to 4.65 mmol/L without transfusions within 7 days prior to laboratory testing; the use of recombinant human erythropoietin is allowed (including as continuous therapy), or hemoglobin level greater than or equal to 5.0 g/dL (greater than or equal to 50 g/L) or greater than or equal to 3.10 mmol/L without the use of erythropoietin and transfusion therapy within 7 days prior to laboratory testing; (4) aspartate aminotransferase (AST) Less than or equal to 2.5 ULN; (5) alanine aminotransferase (ALT) Less than or equal to 2.5 ULN; (6) creatinine clearance greater than 20 mL/min/1.73 m2 calculated using the CKD-EPI formula; (7) total bilirubin less than 2 ULN (except for subjects with congenital bilirubinemia, for example, Gilbert s syndrome, in whom direct bilirubin levels should be Less than or equal to 2 ULN); (8) albumin-corrected serum calcium less than 14 mg/dL (less than 3.5 mmol/L); or free ionized calcium less than 6.5 mg/dL (less than 1.6 mmol/L). 9. Consent of men and women of childbearing potential to use highly effective methods of contraception starting from signing of the informed consent form, throughout the study and for 3 months after receiving the last dose of daratumumab in the study, and to refrain from egg (sperm) donation during this period. For the purposes of the study, a woman is considered of childbearing potential if she is postmenarchal, has not reached
Exclusion criteria
Exclusion criteria: Subjects will not be allowed to participate in the study if they meet any of the following criteria 1.Subjects who received daratumumab or other anti-CD38 therapy, excluding subjects who have received no more than one dose of daratumumab within greater than 1 year prior to randomization, with no evidence of refractory disease or daratumumab intolerance. 2.Subjects treated for multiple myeloma within 2 weeks or 5 half-lives (whichever is shorter) before the date of randomization, except for a short course of glucocorticoids (equivalent to 40 mg/day of dexamethasone for up to 4 days) as rescue treatment. 3.Autologous hematopoietic stem cell transplantation within 12 weeks prior to the date of randomization. 4.Allogeneic hematopoietic stem cell transplantation, regardless of timing. 5.Scheduled hematopoietic stem cell transplantation prior to progressive disease during this study. 6.Subjects with plasma cell leukemia (greater than 2 109/L of circulating plasma cells in peripheral blood), POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammapathy, skin lesions) or amyloidosis. 7.Subjects with Waldenstrom macroglobulinemia or other concomitant diseases with hyperproduction of monoclonal IgM (M-protein) in the absence of clonal proliferation of plasma cells with lytic bone involvement. 8.A history of other malignancies within the last 5 years, with the exception of squamous cell and basal cell skin cancer, cervical, breast carcinoma in situ, or other non-invasive malignancies that, in the Investigator s opinion are considered to have been adequately treated and have a minimal risk of recurrence for 5 years. 9.Plasmapheresis within 28 days prior to randomization. 10.Clinical signs of meningeal involvement of multiple myeloma. 11.Concomitant diseases: COPD (with forced expiratory volume in 1 second less than 50 % of the required values), moderate or severe persistent asthma, or a history of asthma within the previous 2 years, or any uncontrolled asthma (subjects with controlled intermittent asthma or controlled mild persistent asthma may be included). 12.HIV-infection, active HBV infection, hepatitis C. Subjects with positive HBsAg cannot be included in the study. Subjects with positive anti-HBcor antibodies should undergo PCR tests for HBV DNA (subjects who tested positive cannot be included in the study). Subjects who have a positive result of a test for anti-HBs do not need to undergo PCR testing for HBV DNA. Subjects who tested positive for anti-HCV antibodies can be included if they had negative results of PCR test for HCV RNA. 13.Subjects with severe concomitant disorders, life-threatening acute complications of the indication treated (including massive pleural, pericardial, or peritoneal effusions requiring intervention, pulmonary lymphangitis, bleeding or organ perforation) at the time of signing of the informed consent form and during the screening period. 14.Concomitant diseases and/or conditions that may interfere with the procedures or results of the study or, in the Investigator s opinion, increase the risks of participating in this study (e.g., active systemic infection, uncontrolled diabetes mellitus, acute diffuse interstitial lung disease). 15.Clinically significant cardiovascular disorders, including: (1) stable angina pectoris, functional class III IV, (2) unstable angina and/or m
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall response rate (at least partial response, PR) according to IMWG (International Myeloma Working Group) criteriaTimepoint: 24 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 1.Stringent complete response (sCR) rate according to IMWG criteria; 2. complete response (CR) rate according to IMWG criteria; 3. very good partial response (VGPR) rate according to IMWG criteria; 4. duration of response; 5. progression-free survival; 6. time to progression; 7. time to response; 8. overall survival. Timepoint: Till End of the study | — |
Countries
Belarus, India, Pakistan, Russian Federation
Contacts
Public ContactDr Viral Shah
Spectrum Clinical Research Pvt. Ltd.
Outcome results
None listed