Isatuximab for Multiple myeloma | Newly diagnosed multiple myeloma

Inclusion criteria

• {"criterion_text":"- Age ≥ 70 years\n- Able to provide written informed consent in accordance with federal, local, and institutional guidelines\n- 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\n- No prior treatment for multiple myeloma\n- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2\n- 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%\n- Adequate organ and bone marrow function within the 21 days prior to randomization defined by: o Bilirubin < 2 times the upper limit of normal (ULN), Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 times the ULN o Absolute neutrophil count (ANC) ≥ 750/mm3 (growth factor support for max 3 days allowed to achieve this value) o 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.) o Platelet count >50,000/mm3 o Calculated or measured creatinine clearance (CrCl) of ≥30 mL/min/1.73m2 (Calculation should be based on the MDRD formula (age, gender, black/non- black, weight, height))"}

Exclusion criteria

• {"criterion_text":"- ECOG status >2\n- Extended field radio therapy (more than 3 fields) within the 21 days prior to randomization\n- Contraindication to isatuximab, dexamethasone, lenalidomide or any of the required concomitant drugs or supportive treatments, including hypersensitivity to antiviral drugs\n- 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\n- Active infection within the 14 days prior to randomization requiring systemic antibiotics and/or antiviral therapy\n- Uncontrolled hypertension or uncontrolled diabetes despite medication\n- Significant neuropathy (Grade 2 with pain or Grade 3 or higher) within the 14 days prior to randomization\n- Known cirrhosis\n- 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.)\n- Participation in another interventional study within the 28 days prior to randomization\n- Major surgery (except kyphoplasty) within the 28 days prior to randomization\n- Patients unlikely to tolerate Rd\n- 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.\n- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)\n- Plasma cell leukemia (> 2.0 x 10^9/L circulating plasma cells by standard differential)\n- Myelodysplastic syndrome\n- Smoldering Myeloma and MGUS\n- 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\n- History of or current amyloidosis\n- Glucocorticoid therapy within the 14 days prior to randomization that exceeds an accumulated dose of 160 mg dexamethasone or 1000 mg prednisone"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"MRD negativity defined by NGF (next generation flow) at 10^-5 after end of induction treatment."}

Secondary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Responses assessed according to IMWG criteria (ORR, PR, VGPR, CR)."}
• {"endpoint_text":"- To compare the Progression-free (PFS) and Overall Survival (OS) between the two arms.","definition_or_measurement_approach":"PFS and OS compared between arms; standard definitions of progression and survival apply (not further specified in CTIS record)."}
• {"endpoint_text":"- To evaluate the proportion of patients with MRD negativity (defined by NGF at 10^-5) after 12 months (13 cycles) of maintenance treatment.","definition_or_measurement_approach":"MRD negativity defined by NGF at 10^-5 after 12 months (13 cycles) of maintenance treatment."}
• {"endpoint_text":"- To evaluate the Time to Progression (TTP) in each arm.","definition_or_measurement_approach":"Time to Progression measured per protocol definitions (not further specified in CTIS record)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"PFS evaluated in cytogenetic subgroups defined by del(17p), t(4;14), t(14;16) and additionally with amp1q21."}
• {"endpoint_text":"- To evaluate the Duration of Response in each arm.","definition_or_measurement_approach":"Duration of Response evaluated per protocol (not further specified in CTIS record)."}
• {"endpoint_text":"- To evaluate safety in both treatment arms.","definition_or_measurement_approach":"Safety assessments in both arms per protocol (AE/SAE reporting per standard definitions)."}
• {"endpoint_text":"- To assess disease-specific and a generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility and health status.","definition_or_measurement_approach":"HRQL assessed using disease-specific and generic instruments (EORTC QLQ-C30, QLQ-MY20, EQ-5D-5L are included in documents)."}
• {"endpoint_text":"- To evaluate PFS of potential second line therapy.","definition_or_measurement_approach":"PFS of subsequent second-line therapies evaluated per protocol (not further specified in CTIS record)."}

Austria

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

27-10-2025

Processing Time Days

416

Number Of Sites

9

Number Of Participants

78

Greece

Earliest CTIS Part Ii Submission Date

06-09-2024

Latest Decision Or Authorization Date

22-10-2025

Processing Time Days

411

Number Of Sites

3

Number Of Participants

60

Primary sponsor

Full Name

Arbeitsgemeinschaft Medikamentoese Tumortherapie gGmbH

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Austria

Contract research organisations

Name

Health Data Specialists Consulting Services Organization And Conduct Of Studies Single Member S.A.

Responsibilities

Contracts with sites, submission of SAE/SUSAR-line listings and safety reports

Name

Assign Data Management And Biostatistics GmbH

Third parties

• {"country":"Greece","full_name":"Health Data Specialists Consulting Services Organization And Conduct Of Studies Single Member S.A.","duties_or_roles":"Contracts with sites, submission of SAE/SUSAR-line listings and safety reports","organisation_type":"Pharmaceutical company"}
• {"country":"Austria","full_name":"Universitaet Wien","duties_or_roles":"Microbiom analysis","organisation_type":"Educational Institution"}
• {"country":"Spain","full_name":"Universidad De Navarra","duties_or_roles":"Isolation of bone marrow myeloma cells for next generation flow (NGF)","organisation_type":"Educational Institution"}
• {"country":"Austria","full_name":"Assign Data Management And Biostatistics GmbH","duties_or_roles":"","organisation_type":"Pharmaceutical company"}