Newly diagnosed, symptomatic multiple myeloma in elderly patients MedDRA version: 16.1 Level: HLT Classification code 10028229 Term: Multiple myelomas System Organ Class: 100000004851
Conditions
Interventions
Trade Name: SARCLISA
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Isatuximab
CAS Number: 1461640-62
Concentration unit: mg/ml milligram(s)/millilitre
Concentration t
Sponsors
AGMT gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
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) o Serum M protein =0.5 g/dL measured using serum protein immunoelectrophoresis and/or o Urine M protein =200 mg/24 hours measured using urine protein immunoelectrophoresis and/or o 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: o Bilirubin 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.) o Platelet count >50,000/mm3 o 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) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 198
Exclusion criteria
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: o Adequately treated basal cell or squamous cell skin cancer o Carcinoma in situ of the cervix o Prostate cancer = Gleason score 6 with stable prostate-specific antigen (PSA over 12 months) o Ductal breast carcinoma in situ with full surgical resection (i.e., negative margins) o Treated medullary or papillary thyroid cancer o Other tumors with low risk of recurrence/metastases and/or early stage R0 surgery • 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate the benefit of isatuximab in combination with lenalidomide and low-dose dexamethasone followed by isatuximab and lenalidomide maintenance therapy in increasing the proportion of patients with MRD negativity as compared to lenalidomide and low-dose dexamethasone followed by lenalidomide maintenance treatment in patients with newly diagnosed multiple myeloma (NDMM).;Secondary Objective: 1) To evaluate the Overall Response Rate (ORR), Partial Response (PR), Very Good Partial Response (VGPR) and Complete Response (CR) as per International Myeloma Working Group (IMWG) criteria in each arm. 2) To compare the Progression-free (PFS) and Overall Survival (OS) between the two arms. 3) To evaluate the proportion of patients with MRD negativity (defined by NGF at 10^-5) after 12 months (13 cycles) of maintenance treatment. 4)To evaluate the Time to Progression (TTP) in each arm. 5) To evaluate the PFS in high risk cytogenetic population defined as patients carrying a) del(17p), t(4;14), t(14;16) in each arm and b) the same aberrations plus amp1q21. 6) To evaluate the Duration of Response in each arm. 7) To evaluate safety in both treatment arms. 8) To assess disease-specific and a generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility and health status. 9) To evaluate PFS of potential second line therapy. ;Primary end point(s): To evaluate the proportion of patients with MRD negativity (defined by NGF (next generation flow) at 10^-5) after end of induction treatment in the two arms.;Timepoint(s) of evaluation of this end point: End of induction treatment (8 cycles á 28 days). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) To evaluate the Overall Response Rate (ORR), Partial Response (PR), Very Good Partial Response (VGPR) and Complete Response (CR) as per International Myeloma Working Group (IMWG) criteria in each arm. 2) To compare the Progression-free (PFS) and Overall Survival (OS) between the two arms. 3) To evaluate the proportion of patients with MRD negativity (defined by NGF at 10^-5) after 12 months (13 cycles) of maintenance treatment. 4)To evaluate the Time to Progression (TTP) in each arm. 5) To evaluate the PFS in high risk cytogenetic population defined as patients carrying a) del(17p), t(4;14), t(14;16) in each arm and b) the same aberrations plus amp1q21. 6) To evaluate the Duration of Response in each arm. 7) To evaluate safety in both treatment arms. 8) To assess disease-specific and a generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility and health status. 9) To evaluate PFS of potential second line therapy. ;Timepoint(s) of evaluation of this end point: For secondary endpoints 1-8: after a maximum of 32 treatment cycles (8 cycles of induction therapy (á 28 days) and 24 cycles (á 28 days) of maintenance treatment) For secondary endpoint 9: after end of treatment according to protocol (32 treatment cycles), progression or intolerability | — |
Countries
Austria, Greece, Serbia
Contacts
Public ContactClinical Trial Lead Manager
AGMT gGmbH
Outcome results
None listed