Phase 2 Multicenter Open-Label Study of Ixazomib, Iberdomide, and Dexamethasone in Elderly Patients with Multiple Myeloma at First Relapse
- Trial ID
- 2024-516257-44-00
- Protocol
- RC21_0169 IFM2021-03
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the rate of patients with **multiple myeloma** achieving a very good partial response (VGPR) or better when treated with the oral combination of Iberdomide, Ixazomib, and Dexamethasone. This is clinically relevant as achieving VGPR or better is associated with improved patient outcomes and can be indicative of the treatment's efficacy in managing the disease.
Secondary objectives include:
- Evaluating the safety and tolerability of the combination of Iberdomide, Ixazomib, and Dexamethasone, as well as the safety and efficacy of Iberdomide plus Ixazomib from Cycle 7 onwards.
- Assessing overall survival (OS), progression-free survival (PFS), time to progression (TTP), duration of response (DOR), duration of therapy (DOT), and time to response (TTR).
- Evaluating the overall response rate (ORR).
- Assessing ORR, PFS, TTP, and OS in patients previously exposed to lenalidomide, as well as in those refractory to lenalidomide.
- Evaluating biological prognosis factors influencing outcomes and response.
- Assessing the impact of frailty scores (IMWG, IFM) on PFS and OS.
- Evaluating the quality of life (QoL).
- Assessing the molecular and immune profile of patients with relapsed myeloma previously exposed to lenalidomide, with or without anti-CD38 monoclonal antibody, through bone marrow aspirate to support translational research projects.
Participants
The clinical trial focuses on evaluating the efficacy of a treatment regimen for **multiple myeloma**. The study population includes both male and female participants aged 70 years and older. Participants are required to have a good general health status, as indicated by an Eastern Collaborative Oncology Group (ECOG) performance score of 2 or less, and a life expectancy of more than six months. The trial does not involve a vulnerable population. Participants must have symptomatic multiple myeloma at first relapse and have undergone one prior line of therapy. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations include adherence to a pregnancy prevention plan for Iberdomide, and male participants must agree to specific contraceptive measures. The selection criteria ensure that participants have measurable disease and meet specific laboratory parameters, such as adequate neutrophil and platelet counts, liver function tests, and creatinine clearance. The trial population was selected based on these criteria to ensure the safety and efficacy of the treatment under investigation.
Plans and Procedures
The clinical trial is a multi-center, open-label, phase 2 study designed to evaluate the efficacy of a combination therapy consisting of **ixazomib citrate**, **iberdomide**, and **dexamethasone** in elderly patients with **multiple myeloma** at first relapse. The primary objective is to assess the rate of patients achieving a very good partial response (VGPR) or better. The trial employs a non-randomized, open-label design, allowing for direct observation of treatment effects without the use of a placebo or blinding. The estimated duration of the trial is from December 2021 to June 2028, with the primary endpoint being the VGPR rate or better using International Myeloma Working Group (IMWG) criteria.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, performance score, and disease status. The inclusion criteria specify that participants must be 70 years or older, have a life expectancy greater than six months, and have symptomatic multiple myeloma at first relapse. Following the screening, participants will attend regular follow-up visits to monitor treatment response and adverse events, with assessments conducted at three and six months of treatment. The end-of-study visit will occur upon completion of the treatment period or earlier if the participant experiences disease progression or unacceptable toxicity.
The expected length of participant involvement is up to 60 months, depending on individual response and tolerance to the treatment regimen. Conditions that may lead to early termination from the study include withdrawal of consent, non-compliance with study procedures, or the occurrence of severe adverse events. Secondary endpoints include the number of adverse events, overall response rate (ORR), time to progression (TTP), time to response (TTR), duration of response (DOR), and overall survival (OS). The study will also explore biological prognostic factors and assess quality of life using EQ5D and SF36 scales.
Treatment
The clinical trial involves the administration of **ixazomib citrate**, a chemical compound provided in **capsule** form. The maximum daily dose of ixazomib citrate is 3 mg, with a total maximum dose of 540 mg over a treatment period of 60 days. The route of administration is **oral use**, and the medication is not formulated for pediatric use. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the prescribed regimen.
**Dexamethasone sodium phosphate** is another investigational product used in this study, provided in **tablet** form. The maximum daily dose is 20 mg, with a total maximum dose of 320 mg over a 6-day treatment period. This medication is also administered orally and is not intended for pediatric patients. Participant adherence to the dosing schedule is closely monitored to maintain the integrity of the trial results.
The study also includes the administration of **iberdomide**, a chemical substance available in **capsule** form. The maximum daily dose is 1.6 mg, with a total maximum dose of 2016 mg over a 60-day treatment period. Iberdomide is administered orally, and like the other investigational products, it is not designed for pediatric use. Monitoring of participant compliance with the dosing schedule is an integral part of the trial protocol.
All investigational products are administered as part of a combination therapy aimed at evaluating the rate of patients achieving a very good partial response or better in elderly patients with **multiple myeloma** at first relapse. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The study is conducted under strict adherence to the dosing schedules and participant compliance is rigorously monitored to ensure the validity and reliability of the trial outcomes.
Efficacy
The efficacy of the clinical trial will be assessed primarily by evaluating the rate of patients achieving a **Very Good Partial Response (VGPR)** or better, using the International Myeloma Working Group (IMWG) criteria. This primary endpoint will determine the effectiveness of the oral combination of Iberdomide, Ixazomib, and Dexamethasone in elderly patients with multiple myeloma at first relapse.
Secondary endpoints include a comprehensive assessment of the overall response rate (ORR), which encompasses Partial Response (PR), VGPR, Complete Response (CR), and minor response (MR) to the treatment regimen. These responses will be evaluated according to IMWG criteria at 3 months and 6 months of treatment. Additional secondary endpoints involve measuring the time to progression (TTP), time to response (TTR), duration of response (DOR), and duration of therapy (DOT). Overall survival (OS) will also be monitored, defined as the time from inclusion to the date of death due to any cause.
Further assessments will include the evaluation of fragility scores using IMWG and IFM Kumar Lancet Oncol 2016 criteria at the time of inclusion. The study will also explore the value of biological prognostic factors such as ISS stage and specific cytogenetic markers, including del(17p), t(4;14), t(14;16), t(14;20), amp(1q), and del(1p). Baseline bone marrow aspirates will support translational research projects, including plasma cell profiling and immunoprofiling. Quality of life will be assessed using EQ5D and SF36 scales.
Inclusion and Exclusion 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 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)
- 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.
Exclusion 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, cognitive 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
- Known intolerance to steroid therapy
- History of hypersensitivity to any of the study medications, their analogues, or excipients in the various formulations, or to study-required co medication
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Yet Recruiting | 14 Dec 2021 | 80 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
IBERDOMIDE 1.6mg | Test | CAPSULE | ORAL USE | 1.6 | 60 | PRD9084373 |
IBERDOMIDE 1.3mg | Test | CAPSULE | ORAL USE | 1.3 | 60 | PRD12257350 |
IDERDOMIDE 1mg | Test | CAPSULE | ORAL USE | 1 | 60 | PRD12257351 |
ixazomib citrate | Test | CAPSULE | ORAL USE | 3 | 60 | PRD1873527 |
Dexaméthasone | Test | SOLUTION FOR INJECTION | ORAL USE | 20 | 6 | PRD959822 |
IDERDOMINE 0.75mg | Test | CAPSULE | ORAL USE | 0.75 | 60 | PRD12257352 |