CTRI/2024/10/074981尚未招募3 期
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
Bristol Myers Squibb India Private Limited8 个研究点 分布在 1 个国家目标入组 760 人开始时间: 2024年11月15日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 760
- 试验地点
- 8
- 主要终点
- 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)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •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
- •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.
- •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.
- •Subject must have received prior treatment with a lenalidomide-containing regimen.
- •Subject achieved minimal response [MR] or better to at least 1 prior antimyeloma therapy.
- •Subject must have documented disease progression during or after their last antimyeloma regimen.
- •Subject has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or
- •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.
- •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.
- •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.
- •Females must agree to refrain from donating eggs in accordance with the Global PPP for mezigdomide or pomalidomide.
- •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.
- •All male and female subjects must also follow all other requirements defined in the Global PPP for mezigdomide or pomalidomide.
排除标准
- •The presence of any of the following will exclude a subject from enrollment
- •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.
- •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.
- •Subject with prior treatment with mezigdomide or pomalidomide.
- •Subject with any investigational agents within 28 days or 5 half-lives (whichever is shorter) of initiating study treatment.
- •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.
- •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.
- •Radiation therapy, other than local palliative therapy, for myeloma associated bone lesions within 14 days of initiating study treatment.
- •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.
- •Subject has plasma cell leukemia, Waldenstrom’s macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or light-chain amyloidosis.
- •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.
- •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.
- •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.
- •Subject has any condition that confounds the ability to interpret data from the study
- •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).
- •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).
- •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.
- •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
- •Subject with gastrointestinal disease or surgery (eg, gastric bypass surgery) that may significantly alter the absorption of mezigdomide and/or other oral study treatment.
- •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
- •Subject has received immunosuppressive medication within the last 14 days of initiating study treatment.
- •The following are exceptions to this criterion: a.
- •Systemic corticosteroids at doses that do not exceed 10 mg/day of prednisone or the equivalent.
- •Steroids as premedication for hypersensitivity reactions (eg, computed tomography [CT] scan premedication).
- •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.
- •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
- •Subject who has had a live vaccine within 3 months of start of study therapy.
- •Known positive HIV status.
- •Refer to Section 6.
- •For country-specific requirements, see APPENDIX I.
- •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.
- •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.
- •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.
- •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.
结局指标
主要结局
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)
时间窗: at baseline, 8 Months and until Progression free | survival up to 5 years or study achieves | endpoints
次要结局
- 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 baseline, 24 weeks & 32 weeks)
- Overall Response (OR)(at C1D1, C2D1, C3D1, C4D1, C5D1, C5D1, C6D1, C7D1, C8D1, C9D1,Disease progression)
- Complete Response((CR) or better)
- Very Good Partial(Response (VGPR) or)
- Time to Response((TTR))
- Duration of Response((DOR))
- Time to Progression((TTP))
- Time to Next Treatment((TTNT))
- Progression-free(Survival 2 (PFS-2))
- Minimal Residual(Disease (MRD))
- Safety(screening day, at C1D1, C2D1, C3D1, C4D1, C5D1, C5D1, C6D1, C7D1, C8D1, C9D1 with Type, frequency, seriousness & severity of adverse events (AEs), and)
- Health Related Quality(of Life (HRQoL))
研究者
研究点 (8)
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