A Multi-center Open-label Phase 2 Study of Ixazomib, Iberdomide and Dexamethasone in Elderly Patients With Multiple Myeloma at First Relapse."

Inclusion criteria

• Age > 70 years
• Eastern Collaborative Oncology Group (ECOG) performance score of ≤2
• Life expectancy > 6 months
• Voluntary written informed consent must be given before performance of any study-related procedure not part of normal medical care, with the understanding that the subject may withdraw consent at any time without prejudice to future medical care.
• Symptomatic multiple myeloma (MM) at first relapse, as defined below:

• Symptomatic multiple myeloma according to international criteria.(Rajkumar et al, 2014)
• Relapsed MM is defined as previously treated MM that progresses and requires initiation of salvage therapy.
• Subject must have received one prior line of therapy for at least 3 cycles.
• Subject has measurable disease at Screening, defined at least one of the following:

• Serum M-protein ≥ 0.5 gram (g)/deciliter (dL), OR
• Urine M-protein ≥ 200 mg in 24 hours, OR
• Serum immunoglobulin free light chain (FLC) ≥ 10 mg/dL provided serum FLC ratio is abnormal.
• Subjects must meet the following laboratory parameters, per laboratory reference range (performed at most 15 days before cycle 1 day 1):

• Absolute neutrophil count (ANC) ≥ 1000/microliter (μL). Subjects may use growth factor support to achieve ANC eligibility criteria.
• Platelet count ≥ 75,000 /mm3 for subjects in whom < 50% of bone marrow nucleated cells are plasma cells; or a platelet count ≥ 50,000/mm3 for subjects in whom > 50% of bone marrow nucleated cells are plasma cells. It is not permissible to transfuse subjects to achieve minimum platelet counts within 3 days before study.

--AST and ALT ≤ 3 × upper limit of normal (ULN).

• Total bilirubin ≤ 1.5 × ULN. Subjects with documented Gilbert's syndrome may have bilirubin > 1.5 × ULN with the approval of the Primary Therapeutic Area Medical Director
• Creatinine clearance (CrCl) ≥ 30 milliliter (mL)/minute (min) (using Cockroft and Gault Formula)
• Patient should comply with Celgene's pregnancy prevention plan for Iberdomide (please see appendix 8 Iberdomide Pregnancy Prevention Plan for subjects in clinical trials)
• Female patients who:

• are postmenopausal for at least 24 months before the screnning visit, OR
• are surgically sterile (have undergone a hysterectomy or bilateral oophorectomy)
• Men even if surgically sterilized must agree to not father a child and agree to practice complete abstinence or to use a condom during therapy and dose interruptions and for 90 days after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential or pregnant.

Non-inclusion Criteria:

• Subject is refractory to bortezomib, defined as progression on or within 60 days of the last dose of bortezomib.
• Subject has had prior treatment with ixazomib, carfilzomib, pomalidomide or iberdomide
• Subject has any of the following conditions:

• Non-secretory or oligo-secretory MM
• Light chain Amyloidosis (AL Amyloidosis)
• POEMS syndrome Waldenström macroglobulinemia
• Known Human Immunodeficiency Viral (HIV) infection
• Active hepatitis B or C infection based on blood screen tests
• Significant cardiovascular or pericardial disease, including uncontrolled angina, hypertension, arrhythmia, recent myocardial infarction within 6 months, congestive, heart failure New York Heart Association (NYHA) Class ≥ 3
• Major surgery within 4 weeks prior screening
• Acute infections requiring parenteral therapy (antibiotic, antifungal or antiviral) within 14 days
• ≥ Grade 3 Peripheral neuropathy or grade 2 with pain
• Uncontrolled diabetes or uncontrolled hypertension within 14 days
• Any other medical condition that, in the opinion of the Investigator, would adversely affect the subject's participation in the study
• Subject has a history of other active malignancies, including myelodysplastic syndrome (MDS), within the past 3 years prior to study entry, with the following exceptions:

• Adequately treated in situ carcinoma of the cervix uteri or the breast,
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin,
• Prostate cancer Gleason grade 6 or lower AND with stable Prostate Specific Antigen (PSA) levels off treatment,
• Previous malignancy with no evidence of disease confined and surgically resected (or treated with other modalities) with curative intent and unlikely to impact survival during the duration of the study.
• Known intolerance to steroid therapy
• Serious medical or psychiatric illness likely to interfere with participation in study
• Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs
• Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
• Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision