| 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
|
|
|
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
|
|
|
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)
|
|
|
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. |