| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Elderly patients with multiple myeloma at first relapse |
|
| E.1.1.1 | Medical condition in easily understood language |
| elderly patients with multiple myeloma at first relapse |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of the study is to determine the rate of patients achieving very good partial response (VGPR) or better to the oral combination Iberdomide, Ixazomib, Dexamethasone. |
|
| E.2.2 | Secondary objectives of the trial |
· To determine safety and tolerability of associated treatment
. To determine the safety and efficacy of Iberdomide plus Ixazomib (Cycle 7 and more)
. To determine Overall Survival (OS), Progression free survival (PFS), time to progression (TTP), duration of response , duration of therapy , time to response
· To determine Overall Response Rate (ORR)
. To determine ORR, PFS, TTP and OS in patients previously exposed to lenalidomide
.To determine ORR, TTP, PFS and OS in patients refractory to lenalidomide
. To determine biological prognosis factors influencing outcome and response
. Determine the impact of frailty scores on PFS and OS
· Assess Quality of Life
. Determine molecular and immune profile of this population of patients with relapsed myeloma previously exposed to lenalidomide with or without anti-CD38 monoclonal antibody. Bone marrow aspirate will be performed at baseline to support translational research project including: plasma cell profiling , immunoprofiling |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Age > 70 years
2. Eastern Collaborative Oncology Group (ECOG) performance score of ≤ 2.
3. Life expectancy > 6 months
4. 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.
5. 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.
6. Subject must have received one prior line of therapy for at least 3 cycles.
7. 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.
8. Subjects must meet the following laboratory parameters, per laboratory reference range (performed no more than 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 MDRD method)
9. Patient should comply with Celgene’s pregnancy prevention plan for Iberdomide (please see appendix 8 Iberdomide Pregnancy Prevention Plan for subjects in clinical trials)
10. 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)
11. 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. |
|
| E.4 | Principal exclusion criteria |
1. Subject is refractory to bortezomib, defined as progression on or within 60 days of the last dose of bortezomib.
2. Subject has had prior treatment with ixazomib, carfilzomib, pomalidomide or iberdomide
3. Subject has any of the following conditions:
Non-secretory or oligo-secretory MM
Light chain Amyloidosis (AL Amyloidosis)
POEMS syndrome
Waldenström macroglobulinemia
4. Known Human Immunodeficiency Viral (HIV) infection
5. Active hepatitis B or C infection based on blood screen tests
6. 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
7. Major surgery within 4 weeks prior screening
8. Acute infections requiring parenteral therapy (antibiotic, antifungal or antiviral) within 14 days
9. ≥ Grade 3 Peripheral neuropathy or grade 2 with pain
10. Uncontrolled diabetes or uncontrolled hypertension within 14 days
11. Any other medical condition that, in the opinion of the Investigator, would adversely affect the subject's participation in the study
12. 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.
13. Known intolerance to steroid therapy
14. Serious medical, cognitive or psychiatric illness likely to interfere with participation in study
15. Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs
16. Subjects unable or unwilling to undergo antithrombotic prophylactic treatment
17. Person under guardianship, trusteeship or deprived of freedom by a judicial or administrative decision |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary endpoint is the VGPR rate or better (as best response) using IMWG criteria. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| M1, M2, M3, M4, M5, M6, M7 and more |
|
| E.5.2 | Secondary end point(s) |
- Number of adverse events defined by Common Terminology Criteria for Adverse Events (v5)
- ORR including Partial Response (PR), Very Good Partial Response (VGPR), Complete Response (CR) and minor response (MR) to Iberdomide Ixazomib and Dexamethasone will be evaluated according to IMWG criteria at 3 months and 6 months of treatment.
- Time to progression (TTP) is defined as the time in months from inclusion to the date of disease progression or death due to any cause.
- Time to response (TTR) is defined as the time from inclusion to the date of the first response (PR or better)
- Duration of Response (DOR) is defined as the time from the first response (PR or better) to the date of disease progression or death due to any cause.
- Duration of therapy (DOT) is defined as the time from treatment initiation to the last dose of therapy
- Frailty scores (IMWG, IFM Kumar Lancet Oncol 2016) will be assessed at time of inclusion.
- Overall Survival (OS) is defined as the time in months from inclusion to the date of death due to any cause.
- Value of biological prognostic factors as ISS stage, cytogenectic as del(17p), t(4;14), t(14;16), t(14;20), amp(1q) and del(1p) will be explored. Bone marrow aspirate will be performed at baseline to support translational research project including: plasma cell profiling (cereblon, CD38, CD55, CD59 expression), immunoprofiling (T-cell (CD4, CD8) and NK-cell phenotype)
- Quality of life (EQ5D and SF36 scales will be used to assess QOL) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| M1, M2, M3, M4, M5, M6, M7 and more |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
. Determine biological prognosis factors influencing outcome and response
. Determine the impact of frailty scores (IMWG, IFM) on PFS and OS
· Quality of Life (QoL)
.Determine molecular and immune profile of this population of patients with relapsed myeloma previously exposed to lenalidomide with or without anti-CD38 monoclonal antibody.
|
|
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 22 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| It's last visit of last subject cycle 7 and more + 2 years follow-up period |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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