newly diagnosed patients with multiple myeloma and severe renal impairment MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: SARCLISA
Product Name: Isatuximab 100mg/5ml
Product Code: SAR650984
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Isatuximab
CAS Number: 1461640-62-9
Oth
Sponsors
Hellenic Society of Hematology (EAE)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.The patient has signed an informed consent form (ICF), stating that he or she understands the purpose of the procedures required for the study and is willing to participate in the study. The patient must be willing and able to adhere to the prohibitions and restrictions specified in this protocol, as stated in the ICF. 2.Male or female patients aged 18 years or older at the time of the ICF signature. 3.Patients diagnosed with MM based on the International Myeloma Working Group (IMWG) criteria. 4.Patients with severe RI defined as estimated glomerular filtration rate (eGFR) =65 years) yes F.1.3.1 Number of subjects for this age range 31
Exclusion criteria
Exclusion criteria: 1.Prior or current systemic therapy or stem-cell transplantation for any plasma cell dyscrasia, with the exception of emergency use of a short course (the equivalent of dexamethasone 40 mg/day for a maximum of 4 days) of corticosteroids before treatment. 2.History of malignancy (other than MM) within three years before Cycle 1, Day 1 (exceptions are squamous and basal cell carcinomas of the skin, carcinoma in situ of the cervix or breast, or other non-invasive lesion that in the opinion of the Investigator, with concurrence with the Sponsor's medical monitor, are considered cured with minimal risk of recurrence within three years). 3.Clinical signs of meningeal involvement of MM. 4.Clinically significant cardiac disease, including: -Myocardial infarction within six months before Cycle 1, Day 1, or unstable or uncontrolled condition (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV). -Cardiac arrhythmia (Common Terminology Criteria for Adverse Events Grade 3 or higher) or clinically significant electrocardiogram (ECG) abnormalities -ECG showing a baseline QT interval as corrected QTc >470 msec. 5.Known: -Active hepatitis A -To be seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen). Patients with resolved infection (i.e., patients who are positive for antibodies to hepatitis B core antigen [antiHBc] and/or antibodies to hepatitis B surface antigen [antiHBs]) must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are PCR positive will be excluded Exception: Patients with serologic findings suggestive of HBV vaccination (antiHBs positivity as the only serologic marker) AND a known history of prior HBV vaccination, do not need to be tested for HBV DNA by PCR -To be seropositive for hepatitis C (except in the setting of a sustained virologic response, defined as aviremia at least 12 weeks after completion of antiviral therapy) -Known to be seropositive for human immunodeficiency virus. 6.Patient has plasma cell leukemia (>2.0 × 109/L circulating plasma cells by standard differential) or Waldenström’s macroglobulinemia or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) or amyloidosis. 7.Any concurrent medical or psychiatric condition or disease (e.g., active systemic infection, uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) that is likely to interfere with the study procedures or results or that, in the opinion of the investigator, would constitute a hazard for participating in this study. 8.Ongoing =Grade 2 peripheral neuropathy. 9.Patient has had major surgery within two weeks before C1D1, or has not fully recovered from an earlier surgery, or has a surgery planned during the time the patient is expected to participate in the study or within two weeks after the last dose of study drug administration. Note: patients with planned surgical procedures to be conducted under local anesthesia may participate.Kyphoplasty or vertebroplasty are not considered major surgery. 10.Patient has known allergies, hypersensitivity, or intolerance to any of the study drugs, monoclonal antibodies, human proteins, or their excipients (refer to isatuximab Investigator’s Brochure) or known sensitivity to mammalian-derived products. 11.Patient was vaccinated with live vaccines within four weeks prior to C1D1 12.Pregnant or nursing women 13. -FCB
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of induction treatment with isatuximab in combination with bortezomib, cyclophosphamide, and dexamethasone (VCd) on the renal function of newly diagnosed patients with multiple myeloma (NDMM) and severe renal impairment (RI).;Secondary Objective: To evaluate the effect of isatuximab in combination with VCd, followed by lenalidomide maintenance on: Overall response rate (ORR) Progression-Free Survival (PFS) Time to Response (TTR) Duration of Response (DoR) Overall Survival (OS) Minimal Residual Disease (MRD) negativity rate Safety;Primary end point(s): The renal response rate (RRR) at six months of treatment with isatuximab plus VCd. RRR is defined as the proportion of patients who achieve a partial renal (PRrenal) or better response after six months of treatment with isatuximab plus VCd, using the eGFR cut-off values of the IMWG response criteria.;Timepoint(s) of evaluation of this end point: At six months of treatment with isatuximab plus VCd | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Overall response rate (ORR): The proportion of patients who achieve a partial response (PR) or better, assessed by the Investigator using the IMWG criteria, from study treatment initiation to PD, or the initiation of further anti-myeloma treatment, or death, whichever comes first 2.Progression-free survival (PFS): The time from study treatment initiation to the date of first documentation of PD, assessed by the Investigator using the IMWG response criteria, or the initiation of further anti-myeloma treatment, or death from any cause, whichever comes first 3.Time to Response (TTR): The time from study treatment initiation to the date of the first objective response of partial response (PR) or better, assessed with the IMWG response criteria 4.Duration of Response (DoR): - The time from the date of the first objective response to the date of first documented PD, assessed by the Investigator using the IMWG response criteria, or death, whichever occurs first. -DoR will be assessed only for patients who have achieved =PR 5.Overall Survival (OS): The time from study treatment initiation to the date of death from any cause. -OS will be assessed during the response follow-up visits, and for a maximum of 36 months from first patient enrolment. 6.Minimal Residual Disease (MRD) negativity rate: The proportion of patients achieving MRD-negative status, assessed by the Investigator at suspected CR as per IMWG criteria. 7.Safety: The incidence of AEs, TEAEs, and serious adverse events (SAEs) from study treatment initiation until 30 days after the last study treatment. AEs and laboratory parameters will be graded using the NCI-CTCAE version 4.03. Specific safety laboratory tests are planned in case of an infusion reaction ;Timepoint(s) of evaluation of this end point: During the whole study | — |
Countries
Greece
Contacts
Public ContactProf. Terpos
Hellenic Society of Hematology (EAE)
Outcome results
None listed