CTRI/2024/10/074981 [Registered on: 09/10/2024] Trial Registered Prospectively
Last Modified On:
25/11/2025
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Randomized, Parallel Group, Active Controlled Trial
Public Title of Study
OPEN-LABEL STUDY COMPARING MEZIGDOMIDE(CC-92480), BORTEZOMIB AND DEXAMETHASONE (MEZIVd) VERSUS POMALIDOMIDE, BORTEZOMIB AND DEXAMETHASONE (PVd) IN SUBJECTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM)
Scientific Title of Study
A PHASE 3, TWO-STAGE, RANDOMIZED, MULTICENTER, OPEN-LABEL STUDY COMPARING MEZIGDOMIDE(CC-92480), BORTEZOMIB AND DEXAMETHASONE (MEZIVd)VERSUS POMALIDOMIDE, BORTEZOMIB AND DEXAMETHASONE (PVd) IN SUBJECTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM): SUCCESSOR-1
Trial Acronym
SUCCESSOR-1
Secondary IDs if Any
Secondary ID
Identifier
2021-001957-30
EudraCT
CA057-001 Amendment 04 dated 10 May 2023
Protocol Number
NCT05519085
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Shilpi Sinha
Designation
Associate Director, Head RCO India
Affiliation
Bristol Myers Squibb India Pvt. Ltd.
Address
Bristol Myers Squibb India Pvt. Ltd.
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA,
India
Mumbai MAHARASHTRA 4000013 India
Phone
02266288600
Fax
02266288600
Email
Shilpi.Sinha@bms.com
Details of Contact Person Public Query
Name
Shilpi Sinha
Designation
Associate Director, Head RCO India
Affiliation
Bristol Myers Squibb India Pvt. Ltd.
Address
Bristol Myers Squibb India Pvt. Ltd.
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013 (Suburban), MAHARASHTRA,
India
Mumbai MAHARASHTRA 4000013 India
Phone
02266288600
Fax
02266288600
Email
Shilpi.Sinha@bms.com
Source of Monetary or Material Support
Bristol-Myers Squibb India Private Limited,
One International Center, 6th Floor, Tower 1,
Senapati Bapat Marg, Elphinstone (W),
Maharashtra (India) – 400013
Primary Sponsor
Name
Bristol Myers Squibb India Private Limited
Address
One International Centre, 6th Floor, Tower 1, Senapati Bapat Marg, Elphinstone (W), Mumbai - 400013, India
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
NIL
NIL
Countries of Recruitment
Argentina Australia Austria Belgium Brazil Canada Chile China Czech Republic Finland France Germany Greece Ireland Italy New Zealand Poland Portugal Republic of Korea Romania Spain United States of America Japan
Christian Medical College and Hospital Brown Road, 4th Floor, Brown Road, Ludhiana, Punjab-141008, India Ludhiana PUNJAB
08054959525
mjosephjohn@cmcludhiana.in
Dr Abhishek Dudhatra
HCG Aastha Cancer Centre
HCG Aastha Cancer Centre
opp. Bhagawat Vidhyapith,
Sola, Ahmedabad,
Gujarat 380060
Ahmadabad GUJARAT
09978115559
avdudhatra@gmail.com
Dr Anil Singh
Homi Bhabha Cancer Hospital
Homi Bhabha Cancer Hospital, OPD Room No – 4, Ghanti Mill Road, Lahartara, Old Loco Colony, Shivpurwa, Varanasi, Uttar Pradesh - 221010, India Varanasi UTTAR PRADESH
7905004119
anilsingh8520@gmail.com
Dr Biswajit Dubashi
Jawaharlal Institute of Postgraduate Medical Education and Research
Jawaharlal Institute of postgraduate Medical and research, 3rd floor, Super Specialty Block, Dhanvanthri Nagar, Puducherry - 60500, India Pondicherry PONDICHERRY
08056338403
drbiswajitdm@gmail.com
Dr Rohan Bhise
KLES Dr Prabhakar kore hospital
KLES Dr. Prabhakar Kore Hospital and Medical Research Centre, OPD - Medical Oncology, G + 3 floor, Nehru Nagar, Belagavi - 590010, Karnataka, India Belgaum KARNATAKA
09448866712
rohanbhise30@gmail.com
Dr Meet Kumar
Marengo Asia Hospitals
Marengo Asia Hospitals Gurugram (part of North East Health care Pvt Ltd), Ground floor, Room no 804, Golf course, Ext road, Sushant Lok II, Sector - 56, Gjata, Gurugram - 122011, Haryana, India Gurgaon HARYANA
09038791250
kr_meet@yahoo.com
Dr KasiviswanathanT
Meenakshi Mission Hospital & Research center
Meenakshi Mission Hospital & Research Centre, 6th floor, Lake area, Melur road, Madurai - 625107, Tamil Nadu, India Madurai TAMIL NADU
09965606712
kasi.mmhrc@gmail.com
Dr Udip Dilip Maheshwari
MOC Cancer Care & Research Centre
(Unit of Cellcure Cancer Centre Pvt Ltd),
1 to 4, Floor-1st , Shreepati Arcade, August Kranti Marg,
Nana Chowk, Mumbai, Maharashtra, India-400036 Mumbai (Suburban) MAHARASHTRA
Institutional Ethics Committee - Christian Medical College and Hospital
Approved
Institutional Ethics Committee Meenakshi Mission Hospital & Research Centr
Approved
Institutional Ethics Committee, MPMMCC & HBCH
Approved
Institutional Ethics Committee, JIPMER
Approved
Institutional Ethics Committee, KLE Academy of Higher Education and Research (KAHER)
Approved
Mumbai Oncocare Centre IEC Cellcure-Cancer Centre Private Limited
Approved
Regulatory Clearance Status from DCGI
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
Mezigdomide (CC-92480), bortezomib, Dexamethasone
Mezigdomide (CC-92480)(per oral)1 mg bortezomib (SubCuteneous): 1.3 mg per kg Dexamethasone ( peroral): 20mg per kg for 5years or until progression
Comparator Agent
Pomalidomide, Bortezomib, Dexamethasone
Pomalidomide (per oral)4mg Bortezomib (SubCuteneous) 1.3 mg per kg Dexamethasone (per oral) 20 mg per kg for 5 years or until disease progression
Inclusion Criteria
Age From
18.00 Year(s)
Age To
99.00 Year(s)
Gender
Both
Details
Subjects must satisfy the following criteria to be enrolled in the study
1 Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
2 Subject and/or subject’s legal representative must understand and voluntarily sign an ICF according to local regulations prior to any study-related assessments/procedures being conducted. For country-specific requirements, see APPENDIX I.
3 Subject is willing and able to adhere to the study visit schedule and other protocol requirements
4. Subject has documented diagnosis of MM and measurable disease, defined as any of the
following:
4.1 M-protein ≥ 0.5 g/dL by serum protein electrophoresis (sPEP) or
4.2 M-protein ≥ 200 mg/24-hour urine collection by urine protein electrophoresis (uPEP)
or,
4.3 For subjects without measurable disease in sPEP or uPEP : serum free light chain (sFLC) levels more than 100 mg/L (10 mg/dL) involved light chain and an abnormal kappa/lambda FLC ratio.
5. Subject has received 1 to 3 prior lines of antimyeloma therapy. (Note: One line can contain
several phases [eg, induction, (with or without) hematopoietic stem cell transplant, (with or without) consolidation, and/or (with or without) maintenance therapy) See APPENDIX H.
6. Subject must have received prior treatment with a lenalidomide-containing regimen. For country-specific requirements, see APPENDIX I.
7. Subject achieved minimal response [MR] or better to at least 1 prior antimyeloma therapy.
8. Subject must have documented disease progression during or after their last antimyeloma
regimen.
9. Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0,
1 or 2.
10. Females of childbearing potential (FCBP) must agree and adhere to all testing and contraception requirements in the respective Global Pregnancy Prevention Plan (PPP) for mezigdomide or pomalidomide. Duration of contraception for FCBP must be in accordance with the Global PPP for mezigdomide or pomalidomide, or seven months following the last dose of bortezomib, whichever is later.
11. Male subjects must agree and adhere to all contraception requirements in the respective Global PPP for mezigdomide or pomalidomide. Duration of contraception for male subjects must be in accordance with the Global PPP for mezigdomide or pomalidomide, or four months following the last dose of bortezomib, whichever is later.
12. Male subjects must agree to refrain from donating sperm in accordance with the Global PPP
for mezigdomide or pomalidomide, or for four months following the last dose of bortezomib,
whichever is later.
13. Females must agree to refrain from donating eggs in accordance with the Global PPP for
mezigdomide or pomalidomide.
14. Subjects must agree to refrain from donating blood while on study treatment, during dose
interruptions and for at least 28 days following the last dose of study treatment.
15. All male and female subjects must also follow all other requirements defined in the Global
PPP for mezigdomide or pomalidomide.
ExclusionCriteria
Details
The presence of any of the following will exclude a subject from enrollment
1. Subject who has had progression during treatment or within 60 days of the last dose of a
proteasome inhibitor, except as noted below:
a. Subjects who progressed while being treated with, or within 60 days of last dose of bortezomib maintenance given once every 2 weeks or less are not excluded.
2. For subjects with prior treatment of a bortezomib containing regimen, the best response achieved was not a minimal response or better, or subject discontinued bortezomib due to toxicity.
3. Subject with prior treatment with mezigdomide or pomalidomide.
4. Subject with any investigational agents within 28 days or 5 half-lives (whichever is shorter) of initiating study treatment.
a. Participation in any concurrent study where subjects will receive any drug or treatment or any procedure that would interfere with study assessments is not permitted. Subjects who have completed treatment with the prior investigational agent(s) and are currently in Long-term Follow up are permitted.
5. Subject has received any of the following:
a. Plasmapheresis within the last 28 days of initiating study treatment
b. Major surgery (as defined by the investigator) within 28 days of initiating study treatment.
c. Radiation therapy, other than local palliative therapy, for myeloma associated bone lesions within 14 days of initiating study treatment.
d. Use of any systemic antimyeloma drug therapy within 14 days of initiating study treatment.
6. Subject has previously received allogeneic stem cell transplantation at any time during prior
therapy or received autologous stem cell transplantation within 12 weeks of initiating study treatment.
7. Subject has plasma cell leukemia, Waldenstrom’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or light-chain amyloidosis.
8. Subject with known central nervous system (CNS) involvement with myeloma.
9. Subject has any significant medical condition, including active or uncontrolled infection, presence of laboratory abnormality, or psychiatric illness that places the subject at anunacceptable risk for treatment-related complications, if he/she were to participate in the study.
10. Coronavirus disease 2019 (COVID-19) within 7 days for mild or asymptomatic infections or
14 days for moderate/severe infections prior to initiating study treatment. A longer duration
may be needed based on the investigator’s clinical judgment.
10.1 Acute symptoms must have resolved and there are no sequelae that would place the subject at
a higher risk of receiving study treatment, based on investigator assessment in consultation
with the Sponsor Medical Monitor. No repeat/follow-up COVID-19 testing is required.
11. Subject has any condition that confounds the ability to interpret data from the study
12. Subject has any of the following laboratory abnormalities:
a. Absolute neutrophil count (ANC) more than 1,000/microlitre It is not permissible to administer GCSF to achieve minimum ANC levels within 7 days prior to the complete blood count (CBC) which will be used to determine eligibility (or within 14 days prior for pegfilgrastim).
b. Platelet count: more than 75,000/microlitre for subjects in whom more than equal to 50% of
bone marrow nucleated cells are plasma cells (transfusions are not permitted within 7 days prior to the CBC which will be used to determine eligibility).
c. Estimated glomerular filtration rate (eGFR) more than 30 mL/min or requiring dialysis. eGFR
will be calculated using the Modification of Diet in Renal Disease (MDRD) formula.
d. Corrected serum calcium more than 13.5 mg/dL (more than 3.4 mmol/L)
f. Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than 2.5 × upper limit of normal (ULN)
g. Serum total bilirubin more than 1.5 × ULN, or for subjects with documented Gilbert’s syndrome more than 3.0 mg/dL
13. Subject has peripheral neuropathy more than equal to Grade 2
14. Subject with gastrointestinal disease or surgery (eg, gastric bypass surgery) that may significantly alter the absorption of mezigdomide and/or other oral study treatment.
15. Subject has prior history of malignancies, other than MM, unless the subject has been free of the disease for more than equal to 5 years with the exception of the following noninvasive malignancies:
Basal cell carcinoma of the skin
Squamous cell carcinoma of the skin in situ (stage 0)
Carcinoma in situ of the cervix
Carcinoma in situ of the breast
Incidental histologic finding of prostate cancer (T1a or T1b using the TNM [tumor, nodes, metastasis] clinical staging system) or prostate cancer that is curative
16. Subject has received immunosuppressive medication within the last 14 days of initiating study treatment.
The following are exceptions to this criterion:
a. Intranasal, inhaled, topical or local corticosteroid injections (eg, intra-articular injection).
b. Systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or the equivalent.
c. Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication).
17. Administration of strong CYP3A modulators or proton-pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) within 2 weeks of starting study treatment. See Section 8 for administration during the treatment period.
18. Subject has impaired cardiac function or clinically significant cardiac disease, including any of the following:
a. Myocardial infarction within 1 year before randomization, or an unstable or
uncontrolled disease/condition related to or affecting cardiac function (eg, unstable
angina, congestive heart failure New York Heart Association Class III-IV)
b. Uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology
Criteria for Adverse Events [NCI CTCAE] version 5.0 Grade 2 or higher) or clinically
significant electrocardiogram (ECG) abnormalities
19. Subject who has had a live vaccine within 3 months of start of study therapy.
20. Subject is unable or unwilling to undergo protocol required thromboembolism or antiviral prophylaxis
21. Subject is positive for human immunodeficiency virus (HIV), chronic or active hepatitis B, active hepatitis A, or active hepatitis C:
a. Known positive HIV status. Refer to Section 6.1. For country-specific requirements, see APPENDIX I.
b. Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Subjects with resolved infection (ie, subjects who are HBsAg negative but positive for antibodies to hepatitis B core antigen [anti-HBc] and/or antibodies to hepatitis B surface antigen [anti-HBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded. EXCEPTION: Subjects
with serologic findings suggestive of HBV vaccination (anti-HBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR. For country-specific requirements, see APPENDIX I.
c. Known to be seropositive for hepatitis C virus (HCV); anti-HCV antibody positive or HCV- ribonucleic acid (RNA) quantitation positive, except in the setting of a sustained virologic response (SVR), defined as aviremia at least 12 weeks after completion of antiviral therapy.
22. Subject has a history of anaphylaxis or hypersensitivity to thalidomide, lenalidomide (including more than equal to Grade 3 rash during prior thalidomide or lenalidomide therapy), bortezomib, dexamethasone, any other CELMoD agents, or the excipients contained in the formulations, or subject has any contraindications per local prescribing information.
23. Subject is a female who is pregnant, nursing or intends to get pregnant.
Method of Generating Random Sequence
Computer generated randomization
Method of Concealment
Centralized
Blinding/Masking
Open Label
Primary Outcome
Outcome
TimePoints
To compare the progression-free survival (PFS) of mezigdomide, bortezomib and dexamethasone (MeziVd) to that of pomalidomide, bortezomib and dexamethasone (PVd) in subjects with relapsed or refractory multiple myeloma (RRMM)
at baseline, 8 Months and until Progression free
survival up to 5 years or study achieves
endpoints
Secondary Outcome
Outcome
TimePoints
In Stage 1, to determine the dose of mezigdomide in combination with bortezomib & dexamethasone to continue in Stage 2 of the study
at baseline, 24 weeks & 32 weeks
In Stage 1, to determine the plasma concentrations of mezigdomide in combination with bortezomib & dexamethasone
at baseline, 24 weeks & 32 weeks
To compare overall survival (OS) between MeziVd & PVd in subjects with RRMM
at C1D1, C2D1, C3D1, C4D1, C5D1, C5D1, C6D1, C7D1, C8D1, C9D1, progression on the next antimyeloma
treatment or death due to any cause, whichever occurs first
Minimal Residual
Disease (MRD)
negativity
at C1D1, C2D1, C3D1, C4D1, C5D1, C5D1, C6D1, C7D1, C8D1, C9D1Achievement of complete response (CR) or better & MRD negative
(defined at a sensitivity of a minimum of 1 in 105 nucleated cells)
Safety
screening day, at C1D1, C2D1, C3D1, C4D1, C5D1, C5D1, C6D1, C7D1, C8D1, C9D1 with Type, frequency, seriousness & severity of adverse events (AEs), and
relationship of AEs to study treatment
Health Related Quality
of Life (HRQoL)
Evaluation
In Stage 2, at C1D1, C2D1, C3D1, C4D1, C5D1, C5D1, C6D1, C7D1, C8D1, C9D1 & PFS visit
Target Sample Size
Total Sample Size="760" Sample Size from India="20" 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)
15/11/2024
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
10/10/2022
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="5" Months="0" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Not Yet Recruiting
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 study is a 2-stage, randomized, multicenter, open-label, Phase 3 study comparing the efficacyand safety of MEZIGDOMIDE(CC-92480), BORTEZOMIB AND DEXAMETHASONE (MEZIVd)VERSUS POMALIDOMIDE, BORTEZOMIB AND DEXAMETHASONE (PVd) in participants with RRMM who received at least 1 prior line of therapy, Treatment will continue until confirmed PD, death, unacceptable toxicity, or withdrawal of consent. All participants will have an End of Treatment (EOT) visit to collect safety and efficacy assessments.Once the participant completes the end of treatment visit, they will enter the followup period.