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

Study Overview
=================
Brief Summary
-----------------
This is a phase II, multicenter, open-label study to evaluate the rate of patients achieving very good partial response (VGPR) or better to the oral combination Iberdomide Ixazomib Dexamethasone in elderly patients with multiple myeloma at first relapse . The patient population will consist of adult men and women more than 70 years, who meet eligibility criteria. Following the screening period, patients will be enrolled and treated then, they will receive therapy with Iberdomide, Ixazomib and Dexaméthasone during 6 cycles and Iberdomide and Ixazomib until progression.

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

Conditions
-----------------
Multiple Myeloma at First Relapse

Intervention / Treatment
-----------------
* Drug: Ixazomib
* Drug: Iberdomide
* Drug: Dexamethasone Oral


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: assessment of treatment Ixazomib, dexamethasone, iberdomide<br>Iberdomide, Ixazomib and Dexaméthasone during 6 cycles and Iberdomide and Ixazomib until progression | Drug: Ixazomib<br>* Ixazomib 3 mg/day (days 1, 8, 15) cycle 1 to until progress<br>Drug: Iberdomide<br>* Iberdomide 1.6 mg / day (day 1 to 21) cycle 1 to until progress<br>Drug: Dexamethasone Oral<br>* Cycle 1 and 2 Dexaméthasone 20 mg/day on days 1, 8, 15, 22 Cycle 3 to 6 Dexamethasone 10 mg/day on days 1, 8, 15, 22<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients have very good partial response (VGPR) or better | Using IMWG criteria | approximate 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events | Number of adverse events defined by Common Terminology Criteria for Adverse Events (v5) | approximate 18 months | 
| Number of responses | Partial Response (PR), Very Good Partial Response (VGPR), Complete Response (CR) and minor response (MR) will be evaluated according to IMWG | 3 months | 
| Number of responses | Partial Response (PR), Very Good Partial Response (VGPR), Complete Response (CR) and minor response (MR) will be evaluated according to IMWG | 6 months | 
| Number of the death | is defined as the time in months from inclusion to the date of death due to any cause. Subject alive will be censored at the last known alive date. | approximate 18 months | 
| Number of progression | is defined as the time in months from inclusion to the date of disease progression or death due to any cause, using IMWG criteria | approximate 18 months | 
| Percentage of time to progression | is defined as the time in months from inclusion to the date of disease progression or death due to any cause, using IMWG criteria | approximative 18 months | 
| Percentage of duration of response | is defined as the time from the first response (PR or better) to the date of disease progression or death due to any cause | approximative 18 months | 
| Percentage of duration of therapy | is defined as the time from treatment initiation to the last dose of therapy | approximative 18 months | 
| Percentage of time to response | according IMWG | approximative 18 months | 
| Percentage of Overall Response Rate | according IMWG | approximative 18 months | 
| Percentage of value of biological prognostic factors | prognostic factors as ISS stage, cytogenetic as del(17p), t(4;14), | day 1 | 
| Percentage of frailty scores | age, ECOG, comorbidity index | day 1 | 
| Percentage of score of quality of life | To assess Quality of Life EQ5D and SF36 | approximative 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Multiple Myeloma, elderly patients, first relapse, previous exposed, High Risk, Ixazomib, Iberdomide, Dexametasone