Authorised Therapeutic confirmatory (Phase III) Plasma cell myeloma

Isatuximab in combination with lenalidomide and dexamethasone in high-risk smoldering multiple myeloma

EU CTIS ID: 2023-507419-37-00

What this study is testing

- Safety run-in Part: To confirm the recommended dose of isatuximab when combined with lenalidomide and dexamethasone in participants with high-risk smoldering multiple myeloma (SMM) - Randomized Phase 3 Part: To demonstrate the clinical benefit of isatuximab in combination with lenalidomide and dexamethasone in the prolongation of progression free survival when compared to lenalidomide and dexamethasone in participants with high-risk SMM

  • Therapeutic confirmatory (Phase III)

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

  • Participant must be at least 18 years of age inclusive or older
  • Participants who are diagnosed within 5 years with SMM (per International Myeloma Working Group [IMWG] criteria), defined as serum M-protein ≥30 g/L or urinary M- protein ≥500 mg per 24 hour or both, and/or clonal bone marrow plasma cells (BMPCs) 10% to <60%, and absence of myeloma defining events or other related conditions and with high-risk SMM
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 or 2
  • Capable of giving voluntary written informed consent
  • Absolute neutrophil count (ANC) ≥1000/µL (1 × 109/L)
  • Platelets ≥50,000/µL (50 × 109/L)

You likely can't join if

  • -Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): Increased calcium levels: Corrected serum calcium >1 mg/dL above the ULN or >11 mg/dL
  • -Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): Serum involved/uninvolved FLC ratio ≥100 and an involved FLC ≥100mg/L
  • -Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): Whole body magnetic resonance imaging (WB-MRI) or positron emission tomography computed tomography (PET-CT) with more than 1 bone focal lesion (≥5 mm in diameter by MRI)
  • - Clinically significant cardiac or vascular disease within 3 months prior to randomization, e.g. Myocardial Infarction; Unstable Angina; Coronary (e.g. Coronary Artery Bypass Graft, Percutaneous Coronary Intervention) or peripheral artery revascularization, Left Ventricular Ejection Fraction <40%, Heart Failure NYHA III-IV, Stroke, Transient Ischemic Attack, Pulmonary Embolism, other thromboembolic event, cardiac arrhythmia (Grade 3 or higher by NCI-CTCAE Version 5.0)
  • Primary systemic and localized amyloid light chain (AL) amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering myeloma, soft-tissue plasmacytoma, and symptomatic myeloma
  • - Uncontrolled infection within 28 days prior to randomization in Phase 3 or first study intervention administration in safety run-in
See the full eligibility criteria
Who can join
  • Participant must be at least 18 years of age inclusive or older
  • Participants who are diagnosed within 5 years with SMM (per International Myeloma Working Group [IMWG] criteria), defined as serum M-protein ≥30 g/L or urinary M- protein ≥500 mg per 24 hour or both, and/or clonal bone marrow plasma cells (BMPCs) 10% to <60%, and absence of myeloma defining events or other related conditions and with high-risk SMM
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 or 2
  • Capable of giving voluntary written informed consent
  • Absolute neutrophil count (ANC) ≥1000/µL (1 × 109/L)
  • Platelets ≥50,000/µL (50 × 109/L)
  • Total bilirubin ≤3 mg/dL (except Gilbert syndrome, in which direct bilirubin should be - ≤5 mg/dL).
  • Alanine aminotransferase ≤3× upper limit of normal (ULN), aspartate aminotransferase ≤ 3 × ULN.
What rules you out
  • -Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): Increased calcium levels: Corrected serum calcium >1 mg/dL above the ULN or >11 mg/dL
  • -Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): Serum involved/uninvolved FLC ratio ≥100 and an involved FLC ≥100mg/L
  • -Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): Whole body magnetic resonance imaging (WB-MRI) or positron emission tomography computed tomography (PET-CT) with more than 1 bone focal lesion (≥5 mm in diameter by MRI)
  • - Clinically significant cardiac or vascular disease within 3 months prior to randomization, e.g. Myocardial Infarction; Unstable Angina; Coronary (e.g. Coronary Artery Bypass Graft, Percutaneous Coronary Intervention) or peripheral artery revascularization, Left Ventricular Ejection Fraction <40%, Heart Failure NYHA III-IV, Stroke, Transient Ischemic Attack, Pulmonary Embolism, other thromboembolic event, cardiac arrhythmia (Grade 3 or higher by NCI-CTCAE Version 5.0)
  • Primary systemic and localized amyloid light chain (AL) amyloidosis, monoclonal gammopathy of undetermined significance (MGUS), standard risk smoldering myeloma, soft-tissue plasmacytoma, and symptomatic myeloma
  • - Uncontrolled infection within 28 days prior to randomization in Phase 3 or first study intervention administration in safety run-in
  • Patient can be eligible if anti-HBc Immunoglubolin G (IgG) positive (with or without positive anti-HBs) but HBsAg and HBV DNA are negative. If anti-HBV therapy in relation with prior infection was started before initiation of IMP, the anti-HBV therapy and monitoring should continue throughout the study treatment period
  • Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met
  • - Known acquired immunodeficiency syndrome (AIDS)-related illness or known human immunodeficiency virus (HIV) disease requiring antiviral treatment or active hepatitis A (defined as positive hepatitis A antigen or positive IgM). HIV serology at screening will be tested for German participants and any other country where required as per local regulations and serology hepatitis B and C at screening will be tested for all participants.
  • Uncontrolled or active hepatitis B virus (HBV) infection: Patients with positive Hepatitis B surface antigen (HBsAg) and/or HBV Deoxyribonucleic acid(DNA)
  • Patients with antiviral therapy for HCV started before initiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion
  • - Prior exposure to approved or investigational treatments for SMM or multiple myeloma (MM) (including but not limited to conventional chemotherapies, immunomodulatory imid drugs, or Proteasome inhibitors); concurrent use of bisphosphonates or receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitor denosumab is not permitted; however, prior bisphosphonates or once-a-year intravenous bisphosphonate given for the treatment of osteoporosis is permitted
  • -Patients with positive anti-HCV and undetectable HCV ribonucleic acid (RNA) without antiviral therapy for HCV are eligible
  • - Malabsorption syndrome or any condition that can significantly impact the absorption of lenalidomide
  • - Any of the following within 3 months prior to randomization (or first study intervention administration in safety run-in cohort): treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, diverticulitis
  • - Received treatment (eg surgery, radiotherapy, medication) for a malignancy within 3 years of randomization (or first study intervention administration in safety run-in cohort)
  • Active hepatitis C virus (HCV) infection: positive HCV RNA and negative anti-HCV
  • - Ongoing treatment with corticosteroids with a dose >10 mg prednisone or equivalent per day at the time of randomization (or first study intervention administration in safety run-in cohort)
  • -Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): Renal insufficiency: Determined by glomerular filtration rate (GFR) <40 mL/min/1.73 m²(Modification of Diet in Renal Disease [MDRD] Formula) or serum creatinine >2 mg/dL
  • - Women of childbearing potential or male participant with women of childbearing potential who do not agree to use a highly effective method of birth control
  • Vaccination with a live vaccine 4 weeks before the start of the study drug. Seasonal flu vaccines that do not contain live virus are permitted
  • -Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): Anemia (hemoglobin 2 g/dL below lower limit of normal or <10 g/dL or both). Transfusionsupport or concurrent treatment with erythropoietin stimulating agents is not permitted
  • -Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): ≥ 1 bone lytic lesion of ≥5mm in size
  • -Evidence of any of the following calcium, renal failure, anemia, bone lesions (CRAB) criteria or Myeloma Defining Events (SLiM CRAB) detailed below (attributable to the participants SMM involvement): BMPCs ≥60%

The study team makes the final eligibility decision.

Where it's taking place

  • Canada
  • Brazil
  • China
  • United States
  • Korea, Democratic People's Republic of
  • Turkey
  • New Zealand
  • United Kingdom
  • Japan
  • Australia
  • Israel

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Canada; Brazil; China; United States; Korea, Democratic People's Republic of; Turkey and 5 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.