Isatuximab in Combination With Rd Compared to Rd in Elderly Patients (Aged ≥70 Years) With NDMM

This is an interventional treatment trial for Newly Diagnosed Multiple Myeloma focused on measuring Myeloma, Isatuximab, Lenalidomide, Dexamethasone, Elderly, age ≥70 Read More

Inclusion Criteria:

• Age ≥ 70 years
• Able to provide written informed consent in accordance with federal, local, and institutional guidelines

• Patients must have newly diagnosed, symptomatic multiple myeloma with evidence of measurable disease (assessed within 21 days prior to randomization)

  • Serum M protein ≥0.5 g/dL measured using serum protein immunoelectrophoresis and/or
  • Urine M protein ≥200 mg/24 hours measured using urine protein immunoelectrophoresis and/or
  • In subjects without detectable serum or urine M-protein, serum-free light chain (SFLC) ≥100 mg/L (involved light chain) and an abnormal FLC ratio
• No prior treatment for multiple myeloma
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2
• Patients at cardiac risk (NYHA >ll) or pre-existing coronary heart disease, or any other clinically relevant cardiac complication) should be scheduled for a baseline ECHO and can only be included if the LVEF is >40%

• Adequate organ and bone marrow function within the 21 days prior to randomization defined by:

  • Bilirubin < 2 times the upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN
  • absolute neutrophil count (ANC) ≥ 750/mm3 (growth factor support for max 3 days allowed to achieve this value)
  • Hemoglobin >8.0 g/dL (Use of erythropoietic stimulating factors and red blood cell [RBC] transfusion per institutional guidelines is allowed, however the most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin.)
  • Platelet count >50,000/mm3
  • Calculated or measured creatinine clearance (CrCl) of ≥30 mL/min; Calculation should be based on the MDRD formula (age, gender, black/non- black, weight, height)

Exclusion Criteria:

• ECOG status >2
• Patients unlikely to tolerate Rd
• Waldenström macroglobulinemia
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
• Plasma cell leukemia (> 2.0 x 10^9/L circulating plasma cells by standard differential)
• Myelodysplastic syndrome
• Smoldering Myeloma and MGUS

• Second malignancy within the past 5 years except:

  • Adequately treated basal cell or squamous cell skin cancer
  • Carcinoma in situ of the cervix
  • Prostate cancer ≤ Gleason score 6 with stable prostate-specific antigen (PSA over 12 months)
  • Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins)
  • Treated medullary or papillary thyroid cancer
• History of or current amyloidosis
• Glucocorticoid therapy within the 14 days prior to randomization that exceeds an accumulated dose of 160 mg dexamethasone or 1000 mg prednisone
• Extended field radio therapy (more than 3 fields) within the 21 days prior to randomization
• Contraindication to isatuximab, dexamethasone, lenalidomide or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs
• Active congestive heart failure (New York Heart Association [NYHA] Class III or IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, acute diffuse infiltrative pulmonary disease, pericardial disease, or myocardial infarction within 4 months prior to enrolment
• Active infection within the 14 days prior to randomization requiring systemic antibiotics and/or antiviral therapy
• Uncontrolled hypertension or uncontrolled diabetes despite medication
• Significant neuropathy (Grade 2 with pain or Grade 3 or higher) within the 14 days prior to randomization
• Known cirrhosis
• Known human immunodeficiency virus (HIV) seropositivity or active hepatitis C or hepatitis B infection (subjects with past hepatitis B virus [HBV] infection or resolved HBV infection defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen [anti HBc] antibody test are eligible; subjects positive for hepatitis C virus [HCV] antibody are eligible only if polymerase chain reaction [PCR] is negative for HCV RNA.)
• Participation in another interventional study within the 28 days prior to randomization
• Major surgery (except kyphoplasty) within the 28 days prior to randomization
• Any other clinically significant medical disease or social condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent, be compliant with study procedures, or provide accurate information.