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CTRI Number  CTRI/2024/03/063867 [Registered on: 08/03/2024] Trial Registered Prospectively
Last Modified On: 13/11/2025
Post Graduate Thesis  No 
Type of Trial  Interventional 
Type of Study   Drug 
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Study to compare the Efficacy and Safety of BCD-264 in the treatment of Relapsed and Refractory Multiple Myeloma 
Scientific Title of Study   A Double-Blind, Randomized Clinical Study of the Efficacy and Safety of Monotherapy with BCD-264 and Darzalex® in Subjects with Relapsed and Refractory Multiple Myeloma 
Trial Acronym  NIL 
Secondary IDs if Any
Modification(s)  
Secondary ID  Identifier 
BCD-264-2/DARVIVA Protocol version 3 of November 18, 2024  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Shashikant Apte 
Designation  Principal Investigator 
Affiliation  Sahyadri Superspecialty Hospital 
Address  Ground floor OPD ,Department Of Hematology & Bone Marrow Transplant,Sahyadri Superspecialty Hospital 30C Erandwane Karve Road Pune 411004 Maharashtra India

Pune
MAHARASHTRA
411004
India 
Phone  020672115000  
Fax    
Email  shashikant.apte@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Viral Shah 
Designation  Medical Director 
Affiliation  Spectrum Clinical Research Pvt. Ltd. 
Address  401, Spectrum clinical Research Pvt. Ltd., Kshamalaya Building, 4th Floor, 37 New Marine Lines Mumbai 400020

Mumbai
MAHARASHTRA
400020
India 
Phone  02240645100  
Fax    
Email  vshah@spectrumcr.com  
 
Details of Contact Person
Public Query
 
Name  Dr Viral Shah 
Designation  Medical Director 
Affiliation  Spectrum Clinical Research Pvt. Ltd. 
Address  401,Spectrum clinical Research Pvt. Ltd., Kshamalaya Building, 4th Floor, 37 New Marine Lines Mumbai 400020

Mumbai
MAHARASHTRA
400020
India 
Phone  02240645100  
Fax    
Email  vshah@spectrumcr.com  
 
Source of Monetary or Material Support  
JSC BIOCAD, Russia 
 
Primary Sponsor  
Name  JSC BIOCAD, Russia 
Address  198515, Saint Petersburg, Strelna, ul. Svyazi, 38, bldg. 1, office 89 
Type of Sponsor  Pharmaceutical industry-Global 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     Belarus
India
Pakistan
Russian Federation  
Sites of Study
Modification(s)  
No of Sites = 11  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Sunu Lazar Cyriac   Amala Institute of Medical Sciences  Room.no 618,Department of Medical Oncology and Hematology,Amala Institute of Medical Sciences Amala Nagar P.O Thrissur 680555 Kerala India.
Thrissur
KERALA 
0487-2304000

drsunucyriac@gmail.com 
Dr Neeraj Sidharthan   Amrita Institute of Medical Sciences and Research Centre  Professor and HOD, Dept. of Clinical Hematology and Stemcell Transplant Unit, G-block, 4th floor, Amrita Institute of Medical Sciences, AIMS-Ponekkara P.O. Kochi-682041. Kerala, India.
Ernakulam
KERALA 
0484-2853064

neerajsidharthan@aims.amrita.edu 
Dr Basab Bagchi  Chittaranjan National Cancer Institute (CNCI)  Chittaranjan National Cancer Institute (CNCI) Street No. 299, Plot No. DJ-01, Premises No. 02-0321, Action Area 1D, New Town, Rajarhat, Kolkata, West Bengal 700156, India.
Kolkata
WEST BENGAL 
9836655950

basab28@yahoo.co.in 
Dr Biswajit Dubashi   Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER)  Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), JIPMER Academic Centre, 3rd floor, JIPMER Campus Road, Dhanvantari Nagar, Puducherry – 605006.
Pondicherry
PONDICHERRY 
8056338405

dr.biswajitdm@gmail.com 
Dr Maitreyee Bhattacharya   Medical College and Hospital  Professor and HOD, Dept. of Clinical Hematology and Transfusion Medicine, Medical College and Hospital, MCH Building, 3rd Floor, 88 College Street, Kolkata – 700073, West Bengal.
Kolkata
WEST BENGAL 
0332-2551665

mbhattyacharyya@yahoo.co.in 
Dr Himika Mukhopadhyay  Netaji Subhashchandra Bose Cancer Hospital  Netaji Subhas Chandra Bose Cancer Hospital, 3081, Nayabad Ave, New Garia, Kolkata-700094, West Bengal
Kolkata
WEST BENGAL 
8130067049

drhimika.mukherji@gmail.com 
Dr Tuphan Dolai   NRS Medical College and Hospital  Department of hematology, NRS Medical College and Hospital 138 Acharya Jagadish Chandra Bose Rd Sealdah Raja Bazar Kolkata 700014 West Bengal India
Kolkata
WEST BENGAL 
0332-2860033

tkdolai@hotmail.com 
Dr Shashikant Apte   Sahyadri Superspecialty Hospital  Ground floor OPD ,Department Of Hematology & Bone Marrow Transplant,Sahyadri Superspecialty Hospital 30C Erandwane Karve Road Pune 411004 Maharashtra India
Pune
MAHARASHTRA 
0206-7215000

shashikant.apte@gmail.com 
Dr Mukesh Kumar   SMS Hospital  Assistant Professor, Dept. of Oncology, SMS Hospital, Jawahar Lal Nehru Marg, Ashok Nagar, Jaipur, Rajasthan-302001.
Jaipur
RAJASTHAN 
0141-2518222

mukesh.oncologist@gmail.com 
Dr Cecil Ross   St Johns medical college  Department of Medicine, St.Johns Medical College Hospital, Sarjapur Road, Bengaluru, Karnataka- 560034.
Bangalore
KARNATAKA 
8025530070

cecil.ross@stjohns.in 
Dr Jeevan Kumar  Tata Medical Centre  Tata Medical Centre, 14, Major Arterial Road (EW), New Town, Rajarhat, Kolkata-700160, West Bengal.
Kolkata
WEST BENGAL 
9007016755

jeevan.kumar@tmckolkata.com 
 
Details of Ethics Committee
Modification(s)  
No of Ethics Committees= 11  
Name of Committee  Approval Status 
Ethics Committee N S C B C Research Institute  Approved 
Ethics Committee S.M.S. Medical College  Approved 
Ethics Committee, N.R.S. Medical College  Approved 
IEC Intervention Studies JIPMER  Approved 
Institutional Ethics Committee Amala Institute Of Medical Sciences  Approved 
Institutional Ethics Committee Chittaranjan National Cancer Institute  Approved 
Institutional Ethics Committee for Human Research Medical College  Not Applicable 
Institutional Ethics Committee St. Johns Medical College Hospital  Approved 
Institutional Ethics CommitteeAmrita Institute of Medical Sciences  Approved 
Institutional Review Board Tata Medical Center  Approved 
Sahyadri Hospitals Ltd. Ethics committee  Approved 
 
Regulatory Clearance Status from DCGI
Modification(s)  
Status 
Approved/Obtained 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  (1) ICD-10 Condition: C900||Multiple myeloma,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  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 – Cycle 6). Open-label treatment period: BCD-264 once every 4 weeks (Cycle 7 – Cycle 26)  
Comparator Agent  Darzalex  Blinded treatment period: Darzalex IV once weekly for the first 2 therapy cycles, then once every 2 weeks for 16 weeks (Cycle 3 – Cycle 6). 
 
Inclusion Criteria
Modification(s)  
Age From  18.00 Year(s)
Age To  99.00 Year(s)
Gender  Both 
Details  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/µL (1.0 × 109/L); the use of G-CSF is allowed;
(2) platelets greater than or equal to 30,000/µL (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 postmenopause (amenorrhea for greater than or equal to 12 months that cannot be explained by any cause other than menopause), and has not undergone surgical sterilization (removal of ovaries, fallopian tubes and/or uterus).
10. Consent to bone marrow biopsy in the study.
 
 
ExclusionCriteria 
Details  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 myocardial infarction within less than 6 months prior to randomization, (3) chronic heart failure NYHA class III–IV, (4) serious uncontrolled arrhythmia (CTCAE 5.0 grade greater than 2) or clinically significant ECG abnormalities, (5) corrected QT interval according to Fridericia’s formula (QTcF) at screening (12-lead ECG) greater than 470 ms.
16.Hypersensitivity, allergy or intolerability to monoclonal antibodies or any component of the test drug/reference drug.
17.Pregnancy or breastfeeding, as well as planning pregnancy throughout the study and within 3 months after the last dose of daratumumab; for male subjects, planning to conceive a child throughout the study and within 3 months after the last dose of daratumumab.
18.Subject’s inability to follow the study Protocol.
19.Major surgery within less than 14 days prior to randomization, incomplete recovery from surgery, or planned surgery while participating in the study. Kyphoplasty and vertebroplasty are not considered as major surgery and are not an exclusion criterion.
20.Use of any other investigational drugs in any other clinical trials at the time of signing of the informed consent form or within less than 28 days before the planned date of randomization (in the case of anti-myeloma drugs, within 2 weeks or 5 half-lives (whichever is longer) before the date of randomization).

 
 
Method of Generating Random Sequence   Computer generated randomization 
Method of Concealment   Centralized 
Blinding/Masking   Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded 
Primary Outcome  
Outcome  TimePoints 
Overall response rate (at least partial response, PR) according to IMWG (International Myeloma Working Group) criteria  24 Weeks 
 
Secondary Outcome  
Outcome  TimePoints 
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.
 
Till End of the study 
 
Target Sample Size
Modification(s)  
Total Sample Size="452"
Sample Size from India="125" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   Phase 3 
Date of First Enrollment (India)   15/03/2024 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  18/01/2024 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="3"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)
Modification(s)  
Open to Recruitment 
Recruitment Status of Trial (India)  Open to Recruitment 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

This is a double-blind, comparative, randomized phase III clinical study (CS) of the efficacy and safety of monotherapy with BCD-264 and Darzalex in subjects with relapsed and refractory multiple myeloma previously treated with proteasome inhibitors and immunomodulatory drugs, and who had disease progression on prior therapy. Subjects will receive the study therapy for a total of 26 cycles (about 104 weeks from randomization) or until disease progression or signs of unacceptable toxicity, whichever occurs first. The blinded treatment period (up to 6 therapy cycles) will last from randomization to the open label administration of BCD-264 on Day 1 of Cycle 7. The open-label therapy period will start with the open-label administration of BCD-264 on Day 1 of Cycle 7 and end with the EOT visit (maximum 20 therapy cycles). The main objective of the study is to confirm the comparability of the efficacy and safety profiles of BCD-264 and Darzalex as monotherapy for relapsed and refractory multiple myeloma in subjects previously treated with proteasome inhibitors and immunomodulatory drugs, and who had disease progression on prior therapy, which is consistent with the generally accepted practice and recommendations of Russian and international regulatory documents for the development of a biosimilar medicinal product.

 
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