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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 88
- 试验地点
- 2
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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
干预措施: Iberdomide (Drug)
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
干预措施: Iberdomide (Drug)
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
干预措施: Isatuximab (Drug)
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
干预措施: Dexamethesone (Drug)
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
干预措施: Dexamethesone (Drug)
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
干预措施: Bortezomib (Drug)
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
干预措施: Isatuximab (Drug)
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
干预措施: Bortezomib (Drug)
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
干预措施: Iberdomide (Drug)
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
干预措施: Bortezomib (Drug)
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
干预措施: Isatuximab (Drug)
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
干预措施: Iberdomide (Drug)
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
干预措施: Isatuximab (Drug)
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
干预措施: Bortezomib (Drug)
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
干预措施: Iberdomide (Drug)
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
干预措施: Isatuximab (Drug)
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
干预措施: Isatuximab (Drug)
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
干预措施: Iberdomide (Drug)
研究者
Clifton Mo, MD
Principal Investigator
Dana-Farber Cancer Institute