Isatuximab, Iberdomide, Bortezomib, Dexamethasone in Transplant Ineligible/Deferred Newly Diagnosed Myeloma (IsaIberVD)
A Phase 1b/2 Study of the Combination Isatuximab, Iberdomide, Bortezomib, and Dexamethasone in Newly Diagnosed Multiple Myeloma Who Are Transplant Ineligible or Not Intended for Upfront Transplant
This study is to evaluate the combination of isatuximab, iberdomide, bortezomib, and dexamethasone in newly diagnosed multiple myeloma participants who are transplant ineligible or not intended for upfront transplant.
The names of the study drugs used in this research study are:
isatuximab, iberdomide, bortezomib dexamethasone
研究概览
详细说明
This is an open-label, Phase 1b/2, multicenter study which will enroll patients with newly diagnosed multiple myeloma (NDMM), who are transplant ineligible or deferred, to induction followed by maintenance therapy. Participants will be registered in HCC CTMS OnCore before receiving any study-specific treatment, and study treatment is expected to begin within 5 days after registration.
The study drugs used in this research include bortezomib, dexamethasone, isatuximab, and iberdomide (CC-220). The U.S. Food and Drug Administration (FDA) has approved bortezomib and dexamethasone for the initial treatment of multiple myeloma. The FDA has approved isatuximab for initial treatment of multiple myeloma in transplant ineligible patients and for myeloma that has returned after prior treatment. The FDA has not approved iberdomide (CC-220) for the treatment of multiple myeloma. The combination of these drugs, used as induction and maintenance therapy in this study, is considered investigational.
The research study procedures include: screening for eligibility, in-clinic visits, urine tests, questionnaires, PET scans, blood tests, electrocardiograms (ECGs), bone marrow aspiration and biopsy, biobanking, and pregnancy tests for participants who are able to become pregnant.
It is expected that about 88 people will take part in this study. Participants are classified and assigned treatment for induction based on baseline age 70 years status and myeloma frailty score and further assigned for maintenance based on baseline International Myeloma Working Group (IMWG)/International Myeloma Society (IMS) genomic risk classification.
研究类型
注册 (估计的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习联系方式
- 姓名：Cliford Mo, MD
- 电话号码：617-582-7969
- 邮箱：Clifton_Mo@DFCI.HARVARD.EDU
研究联系人备份
- 姓名：Clifford Mo, MD
- 电话号码：617-582-7969
- 邮箱：Clifton_Mo@DFCI.HARVARD.EDU
学习地点
-
-
Massachusetts
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Boston、Massachusetts、美国、02215
- Dana-Farber Cancer Institute
-
接触：
- Clifford Mo, MD
- 电话号码：617-582-7969
- 邮箱：Clifton_Mo@DFCI.HARVARD.EDU
-
首席研究员：
- Cliford Mo, MD
-
Boston、Massachusetts、美国、02215
- Beth Israel Deaconess Medical Center (Bidmc)
-
首席研究员：
- David Avigan, MD
-
接触：
- Clifford Mo, MD
- 电话号码：617-582-7969
- 邮箱：Clifton_Mo@DFCI.HARVARD.EDU
-
-
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Male or female, 18 years of age or older
- Ability to understand and the willingness to sign a written informed consent document
- NDMM based on IMWG criteria with clonal bone marrow plasma cells >10% or biopsy proven bony or extramedullary disease/plasmacytoma (EMD) with any one or more CRAB-features or myeloma defining events (Rajkumar, 2024). (See Appendix G)
- Ineligible for ASCT as assessed by the treating physician or eligible but prefers and agrees to defer ASCT until after induction and maintenance therapy, upon progression or at a later time
Measurable disease defined as at least one of the following:
- Serum M-protein 0.5 g/dL
- Urine M-protein 200 mg/24 hours
- Serum FLC assay: involved FLC 10 mg/dL (100 mg/L) and an abnormal kappa to lambda FLC ratio (< 0.26 or > 1.65)
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (See Appendix A)
Screening Laboratory evaluations with the following parameters:
Absolute neutrophil count (ANC) ≥ 1,000 cells/dL (1.0 x 109/L)
--- Note: Growth factor support is not permitted within 10 days, [14 days for pegfilgrastim], prior to the screening hematologic test.
- Platelet count ≥ 75,000 cells/dL (75 x 109/L) (without transfusions required during the 3 days prior to the screening hematologic test)
- Total Bilirubin ≤ 2 X upper limit of normal (ULN) (except patients with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
- AST (SGOT) and ALT (SGPT) ≤ 3.0 x ULN
- Calculated creatinine clearance (CrCl) 30ml/min (Appendix B)
- Hemoglobin ≥ 8.0 g/dl (red blood cell (RBC) transfusions are permitted)
- Individuals of childbearing potential (IOCBP) must have 2 negative pregnancy tests before initiation of therapy, and agree to ongoing testing, based on the frequency outlined in the Pregnancy Prevention Plan (PPP) (See Appendix H)
- Sexually active IOCBP agree to use protocol-specified contraceptive methods, at least 28 days prior to starting study drug, while taking study drug, including interruptions in study drugs, and for at least 28 days after the last dose of study drug or males sexually active with IOCBP, (including those who have had a vasectomy), agree to use protocol specified contraceptive methods while taking study drug, including interruptions in study drug and for at least 28 days after the last dose of iberdomide, 5 months after isatuximab and 6 months after bortezomib, according to the PPP (See Appendix H)
- All patients (male and female with or without childbearing potential) agree to counseling according to the PPP and to abstain from donating blood products for at least 28 days after the last dose of iberdomide and abstain from donating semen or sperm while taking study drug and for at least 28 days after the last dose of iberdomide according to the PPP (See Appendix H) and for 5 months after the last dose of isatuximab and 6 months after the last dose of bortezomib
- Must be able to take antithrombotic prophylaxis (See Section 5.9.1)
Exclusion Criteria:
Prior therapy for MM. Patients may have received:
- Corticosteroids for management of MM not to exceed equivalent of 160 mg of dexamethasone in a 2-week period and should be stable 7 days prior to the registration.
- Focal palliative radiation for the management of bone pain completed ≥ 7 days prior to registration
Treatment for smoldering myeloma as long as the prior treatment did not include anti-CD38 therapy:
- Patients with a prior history of serious allergic reactions associated with thalidomide, lenalidomide, or pomalidomide should not receive iberdomide as they could be at higher risk of hypersensitivity.
- Resolution of symptoms of prior treatment to ≤ grade 1 or baseline
- Known intolerance to steroid therapy
- Prior history of malignancies, other than MM, will be excluded unless the participant has been free of the disease for ≥ 3 years with the exception of the following non-invasive malignancies: basal or squamous cell skin carcinoma, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histological findings of prostate cancer (T1a or T1b using the Tumor, Node, Metastasis (TNM) clinical staging system), or prostate cancer that is curative
- Central nervous system involvement with MM
- Peripheral neuropathy grade 3, or grade 2 with pain on clinical exam during screening period
- Any medical or psychiatric illness that in the investigator's opinion would impose excessive risk to the patient or would adversely affect participation
- Concurrent uncontrolled cardiovascular conditions (uncontrolled hypertension, uncontrolled arrhythmias, congestive heart failure, unstable angina, grade 3 thromboembolic event or myocardial infarction) in the past 6 months
- Concurrent symptomatic amyloidosis or plasma cell leukemia
- POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes)
- Seropositive for human immunodeficiency virus (HIV-1), chronic or active hepatitis B (defined as positive hepatitis B surface antigen (HepBSAg) or Hepatitis B core antibody (HepBcore Ab) or C (Hep C Ab), or acute hepatitis A. If any history of exposure to hepatitis B or C, then PCR should be negative
- Pregnant or breast feeding female or IOCBP who intend to become pregnant during the study.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in study
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Group A Induction: Age <70 years and Fit (standard-intensity schedule)
Participants <70 years of age and considered fit based on the myeloma frailty score of 0. Induction cycles 1-8; 28-day cycles: Isatuximab: 10 mg/kg Intravenous (IV) Days 1, 8, 15, 22 (Cycle 1 only); Days 1,15 (Cycle 2+) Iberdomide: 1 mg or 0.75 mg Oral (PO) Days 1-21 Bortezomib: 1.3 mg/m2 Subcutaneous (SC) Days 1, 8, 15, 22 Dexamethasone: 20 mg IV or PO Days 1, 2, 8, 9, 15, 16, 22, 23 |
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
|
|
实验性的：Group B Induction: Age ≥70 years and/or Intermediate Fit/Frail (reduced-intensity schedule)
Participants ≥70 years of age and/or considered intermediate fitness and frail based on the myeloma frailty score of >1. Induction cycles 1-8; 28-day cycles: Isatuximab: 10 mg/kg IV Days 1, 8, 15, 22 (Cycle 1 only); Days 1,15 (Cycle 2+) Iberdomide: 1 mg or 0.75 mg PO Days 1-21 Bortezomib: 1.3 mg/m2 SC Days 1, 8, 15 Dexamethasone: 12 mg IV or PO Days 1, 8, 15, 22; 8 mg IV or PO Days 2, 9, 16, 23 |
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
|
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实验性的：Group A Maintenance: High-Risk, Age <70 years and Fit (3-drug schedule)
Participants high-risk per IMWG/IMS criteria, <70 years of age, considered fit based on the myeloma frailty score of 0. Maintenance cycles 1-36; 28-day cycles: (for participants with ≥PR after Induction Cycle 8) Isatuximab: 10 mg/kg IV Days 1, 15 Iberdomide: 1 mg or 0.75 mg PO Days 1-21 Bortezomib: 1.3 mg/m2 SC Days 1, 15 |
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
|
|
实验性的：Group A Maintenance: Standard-Risk, Age <70 years and Fit (2-drug schedule)
Participants standard-risk per IMWG/IMS criteria, <70 years of age, considered fit based on the myeloma frailty score of 0. Maintenance cycles 1-36; 28-day cycles: (for participants with ≥PR after Induction Cycle 8) Isatuximab: 10 mg/kg IV Days 1, 15 Iberdomide: 1 mg or 0.75 mg PO Days 1-21 |
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
|
|
实验性的：Group B Maintenance: High-Risk, Age ≥70 years and/or Intermediate Fit/Frail (3-drug schedule)
Participants high-risk per IMWG/IMS criteria, ≥70 years of age and/or considered intermediate fitness and frail based on the myeloma frailty score of >1. Maintenance cycles 1-36; 28-day cycles: (for participants with ≥PR after Induction Cycle 8) Isatuximab: 10 mg/kg IV Days 1, 15 Iberdomide: 1 mg or 0.75 mg PO Days 1-21 Bortezomib: 1.3 mg/m2 SC Days 1, 15 |
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
|
|
实验性的：Group B Maintenance: Standard-Risk, Age ≥70 years and/or Intermediate Fit/Frail (2-drug schedule)
Participants standard-risk per IMWG/IMS criteria, ≥70 years of age and/or considered intermediate fitness and frail based on the myeloma frailty score of >1. Maintenance cycles 1-36; 28-day cycles: (for participants with ≥PR after Induction Cycle 8) Isatuximab: 10 mg/kg IV Days 1, 15 Iberdomide: 1 mg or 0.75 mg PO Days 1-21 |
Administration, pre-medications and supportive care per protocol
其他名称：
Administration, pre-medications and supportive care per protocol
其他名称：
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Dose-limiting Toxicities (DLT) by Age-Frailty Group [Phase Ib]
大体时间：Assessed continuously during induction cycle 1, up to day 28 + 30 days
|
DLT is defined as any adverse event (AE) that (a) is at least possibly related to study treatment, (b) occur during cycle 1, and (c) meets the following criteria: Hematologic - grade 4 neutropenia lasting >5 days despite supportive care (G-CSF allowed), grade ≥3 febrile neutropenia, grade 3 thrombocytopenia with clinically significant bleeding, grade 4 thrombocytopenia unless clearly attributable to underlying disease, and any grade 5 AE; Non-Hematologic - any grade ≥3 AE (except alopecia), uncontrolled nausea, vomiting, or diarrhea not resolving to ≤ grade 1 with medical management, due to toxicity interruption of >4 doses of iberdomide or >1 dose of isatuximab or bortezomib (infusion-related reactions excluded), due to toxicity inability to initiate cycle 2 day 1 within 7 days.
|
Assessed continuously during induction cycle 1, up to day 28 + 30 days
|
|
Recommended Phase II Dose (RP2D) of Iberdomide by Age-Frailty Group [Phase Ib]
大体时间：Assessed continuously during induction cycle 1, up to day 28 + 30 days
|
The RP2D of iberdomide in combination with fixed doses of isatuximab, bortezomib and dexamethasone is determined by the number of participants experiencing DLT.
There are two potential iberdomide dose levels under evaluation including one de-escalation dose.
The RP2D is defined as the highest dose at which fewer than 2 of 6 patients experience a DLT.
|
Assessed continuously during induction cycle 1, up to day 28 + 30 days
|
|
Complete Response (CR) or Better Rate by Age-Frailty Group [Phase II]
大体时间：Assessed on day 1 of each cycle over 8 induction cycles (cycle duration=4 weeks), up to 32 weeks.
|
CR or better rate is defined as the proportion of participants who achieve a complete response (CR) or stringent CR (sCR) during induction therapy, according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC).
|
Assessed on day 1 of each cycle over 8 induction cycles (cycle duration=4 weeks), up to 32 weeks.
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Induction Grade 3 or 4 Treatment-Related Adverse Event (TRAE) Rate by Age-Frailty Group [Phase Ib]
大体时间：Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.
|
Induction grade 3 or 4 TRAE rate is defined as the proportion of participants who experience a grade 3 or 4 AE based on Common Toxicity Criteria for Adverse Events version 5 (CTCAEv5) with a treatment attribution of possible, probable or definite during induction.
|
Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.
|
|
Induction Feasibility Rate by Age-Frailty Group [Phase II]
大体时间：Assessed after induction cycle 8 (cycle duration=4 weeks), at 32 weeks plus 30 days.
|
Induction feasibility rate is defined as the proportion of participants completing 8 cycles of induction and receiving at least one dose of maintenance treatment.
|
Assessed after induction cycle 8 (cycle duration=4 weeks), at 32 weeks plus 30 days.
|
|
Induction Grade 3 or 4 TRAE Rate by Age-Frailty Group [Phase II]
大体时间：Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.
|
Induction grade 3 or 4 TRAE rate is defined as the proportion of participants who experience a grade 3 or 4 AE based on CTCAEv5 with a treatment attribution of possible, probable or definite during induction.
|
Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.
|
|
Maintenance Grade 3 or 4 TRAE Rate by Age-Frailty Risk Group [Phase II]
大体时间：Assessed continuously during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks + 30 days.
|
Maintenance grade 3 or 4 TRAE rate is defined as the proportion of participants who experience a grade 3 or 4 AE based on CTCAEv5 with a treatment attribution of possible, probable or definite during maintenance.
|
Assessed continuously during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks + 30 days.
|
|
Induction Serious Adverse Event (SAE) Rate by Age-Frailty Group [Phase II]
大体时间：Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.
|
Induction SAE is any untoward medical occurrence at any dose during induction that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization (excluding planned hospitalizations), results in persistent or significant disability or incapacity (namely a substantial disruption of normal life functions), is a congenital anomaly or birth defect, or is considered a medically important event.
|
Assessed continuously during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks + 30 days.
|
|
Maintenance SAE Rate by Age-Frailty Risk Group [Phase II]
大体时间：Assessed continuously during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks + 30 days.
|
Maintenance SAE is any untoward medical occurrence at any dose during maintenance that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization (excluding planned hospitalizations), results in persistent or significant disability or incapacity (namely a substantial disruption of normal life functions), is a congenital anomaly or birth defect, or is considered a medically important event.
|
Assessed continuously during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks + 30 days.
|
|
Induction Best Response by Age-Frailty Group [Phase II]
大体时间：Assessed day 1 of each cycle during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks.
|
Best response over induction will be assessed according to the IMWG-URC including sCR, CR, VGPR, PR, MR, SD or PD.
|
Assessed day 1 of each cycle during induction cycles 1-8 (cycle duration=4 weeks), up to 32 weeks.
|
|
Maintenance Best Response by Age-Frailty Risk Group [Phase II]
大体时间：Assessed day 1 of each cycle during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks.
|
Best response over maintenance will be assessed according to the IMWG-URC including sCR, CR, VGPR, PR, MR, SD or PD.
|
Assessed day 1 of each cycle during maintenance cycles 1-36 (cycle duration=4 weeks), up to 144 weeks.
|
|
Induction Minimal Residual Disease (MRD) Negativity Rate by Age-Frailty Group [Phase II]
大体时间：Assessed after induction cycle 8 (cycle duration=4 weeks), at 32 weeks.
|
Induction MRD-negative rate is defined as the proportion of participants achieving MRD negativity, as assessed by next-generation sequencing (NGS) or next-generation flow cytometry (NGF) with sensitivity of >1 in 10-5 nucleated cells, according to the IMWG-URC.
|
Assessed after induction cycle 8 (cycle duration=4 weeks), at 32 weeks.
|
合作者和调查者
调查人员
- 首席研究员：Cliford Mo, MD、Dana-Farber Cancer Institute
出版物和有用的链接
一般刊物
- Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Blade J, Mateos MV, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau JL, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar SV, Miguel JS, Avet-Loiseau H. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016 Aug;17(8):e328-e346. doi: 10.1016/S1470-2045(16)30206-6.
- Palumbo A, Bringhen S, Mateos MV, Larocca A, Facon T, Kumar SK, Offidani M, McCarthy P, Evangelista A, Lonial S, Zweegman S, Musto P, Terpos E, Belch A, Hajek R, Ludwig H, Stewart AK, Moreau P, Anderson K, Einsele H, Durie BG, Dimopoulos MA, Landgren O, San Miguel JF, Richardson P, Sonneveld P, Rajkumar SV. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015 Mar 26;125(13):2068-74. doi: 10.1182/blood-2014-12-615187. Epub 2015 Jan 27.
- Avet-Loiseau H, Davies FE, Samur MK, Corre J, D'Agostino M, Kaiser MF, Raab MS, Weinhold N, Gutierrez NC, Paiva B, Neri P, Weisel K, Maura F, Walker BA, Bustoros M, Stewart AK, Usmani SZ, Hillengass J, Chng WJ, Keats JJ, Martinez-Lopez J, Sperling AS, Touzeau C, Zhan F, Raje NS, Cavo M, Bolli N, Ghobrial IM, Dhodapkar MV, Jagannath S, Spencer A, Parekh S, Bahlis NJ, Lonial S, Sonneveld P, Bergsagel L, Orlowski RZ, Morgan G, Mateos MV, Rajkumar SV, San Miguel JF, Anderson KC, Moreau P, Kumar S, Prosper F, Munshi NC. International Myeloma Society/International Myeloma Working Group Consensus Recommendations on the Definition of High-Risk Multiple Myeloma. J Clin Oncol. 2025 Aug 20;43(24):2739-2751. doi: 10.1200/JCO-24-01893. Epub 2025 Jun 9.
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- 25-854
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
IPD 计划说明
IPD 共享时间框架
IPD 共享访问标准
IPD 共享支持信息类型
- 研究方案
- 树液
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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