MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: ISATUXIMAB, 1400 mg
Product Name: ISATUXIMAB
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Isatuximab
Current Sponsor code: SAR650984
Concentration unit: mg milligram(s
Sponsors
CHU DE POITIERS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Must be able to understand and voluntarily sign an informed consent form -Must be able to adhere to the study visit schedule and other protocol requirements -Life expectancy of > 6 months -Subject, male or female, must be at least = 65 years of age -Must have a Newly diagnosed Multiple Myeloma requiring therapy (SLiM CRAB criteria) (see appendix 18.2) 1. Monoclonal plasma cells in the bone marrow =10% or presence of a biopsy proven plasmacytoma* *Clonality should be established by showing ?/?-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used and any one or more of the following myeloma defining events: 2. Revised International Myeloma Working Group diagnostic criteria for multiple myeloma Myeloma defining events: ? Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically: • Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL) • Renal insufficiency: creatinine clearance =40 mL per min † or serum creatinine =177 µmol/L (=2 mg/dL) †Measured or estimated by validated equations. ? Anemia: hemoglobin value of =2g/dL below the lower limit of normal, or hemoglobin value =10 g/dL ? Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT ‡ ‡If bone marrow has less than 10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement. ? Any one or more of the following biomarkers of malignancy: ? Clonal bone marrow plasma cell percentage* =60% ? Involved/uninvolved serum free light chain ratio § =100 §These values are based on the serum Freelite assay (The Binding Site Group, Birmingham, UK). The involved free light chain must be =100 mg/L. ? 1 focal lesion on MRI studies (¶Each focal lesion must be 5 mm or more in size.) -Must have measurable disease as defined by any of the following: ? Serum M-protein level =5 g/L or urine M- protein level =200 mg/24 hours; or ? Light chain multiple myeloma: urine M- protein level =200 mg/24 hours or if not quantifiable in urines: Serum immunoglobulin free light chain =10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio * * Any laboratory method can be used. In such a case, the same method must be used along the study for the patient -Must be non-transplant eligible o Newly diagnosed and not considered candidate for high-dose chemotherapy with SCT. o Subject must have Charlson comorbidity index =1 o ECOG =2 -Adequate bone marrow function, documented within 72 hours and without transfusion 72 hours prior to the first intake of investigational product (C1J1) with no growth factor support (one week), defined as: o Absolute neutrophils = 1 x109/L, o Untransfused Platelet count = 75 x109/L, o Hemoglobin = 8.5 g/dL. -Adequate organ function documented within one week prior to the first intake of investigational product (C1J1) defined as: o Serum total bilirubin < 2x upper limit of normal (ULN), o Creatinine clearance = 30ml/min, calculated with MDRD formula, o Serum SGOT/AST or SGPT/ALT < 3x upper limit of normal (ULN). -Subjects affiliated with an appropriate social security system. -A man who is sexually active with a pregnant wo
Exclusion criteria
Exclusion criteria: -Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, or smoldering multiple myeloma. Monoclonal gammopathy of undetermined significance is defined by presence of serum M-protein <3 g/dL; absence of lytic bone lesions, anemia, hypercalcemia, and renal insufficiency related to the M-protein; and (if determined) proportion of plasma cells in the bone marrow of 10% or less. Smoldering multiple myeloma is defined as asymptomatic multiple myeloma with absence of related organ or tissue impairment end organ damage . -Subject has a diagnosis of Waldenstro¨m’s disease, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions. -Subject has prior or current systemic therapy or SCT for multiple myeloma, with the exception of an emergency use of a short course (equivalent of dexamethasone 40 mg/day for a maximum 4 days) of corticosteroids before treatment. -Subject has a history of ongoing malignancy (other than multiple myeloma) within 3 years (date of diagnosis of the malignancy) before the date of study treatment (exceptions are malignancies considered cured with minimal risk of recurrence within 3 years, eventhough the patient receives treatment). -Subject has had radiation therapy/plasmapheresis within 7 days of study treatment -Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma. -Subject known to be seropositive for history of human immunodeficiency virus (HIV) or to have hepatitis A active infection. -Known to have hepatitis B active or uncontrolled infection/hepatitis C active infection -Subject has any clinically significant medical or psychiatric condition or disease in the investigator’s opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results. -Subject has active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics. - Subject has clinically significant cardiac disease, including: omyocardial infarction within 6 months before study treatment, or an unstable or uncontrolled disease/condition related to or affecting cardiac function ouncontrolled cardiac arrhythmia (NCI CTCAE Version 5 Grade =2) or clinically significant ECG abnormalities or LVEF < 40 % -Subject has known allergies, hypersensitivity, or intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine hydrochloride, poloxamer 188, sucrose or any of the other components of study intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents, monoclonal antibodies or human proteins, or their excipients (refer to respective package inserts or Investigator's Brochure). -Known hypersensitivity, allergy to one of the study product (isatuximab, lenalidomide, bortezomib), dexamethasone, boron or to one of the excipients. Allergy to bandages or adhesives (acrylic). -Acute diffuse infiltrative pneumopathy, pericardial disease -Subject has plasma cell leukemia (according to WHO criterion: =20% of cells in the peripheral blood with an absolute plasma cell count of more than 2 × 109/L) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes). -Subject is known or suspected of not being able to comply with the study protoc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate at 8 months the > Very Good Partial Response rate (as best response) in patients with newly diagnosed NTE multiple myeloma.;Secondary Objective: - To determine Overall Survival (OS), Progression free survival (PFS), Time to Progression (TTP), Time to Next Therapy (TTNT) and Event Free survival (EFS) - To determine duration of response (DOR) and time to response (TTR) - To assess responses to the treatment according to IMWG*, ORR (Overall response rate) >PR, >CR (complete response), and best MRD 10-5 rate + sustained 12 and 24 months. -To assess the safety and local tolerability of SC isatuximab + VRd according to CTCAE 5.0. - To assess patient satisfaction with SC isatuximab ;Primary end point(s): The primary endpoint is the VGPR rate or better (as best response) using IMWG criteria (see below).;Timepoint(s) of evaluation of this end point: 8 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •To determine Survivals, Overall Survival (OS), Progression free survival (PFS), Time to Progression (TTP), Time to Next Therapy (TTNT) and Event Free survival (EFS) •To determine duration of response (DOR) and time to response (TTR) •To assess responses to the treatment according to IMWG*, ORR (Overall response rate) ?PR, ?CR (complete response), and best MRD 10-5 rate + sustained 12 and 24 months. •To assess the safety, including infusions reactions, device deficiencies, and local tolerability (injections site reactions) of SC isatuximab + VRd according to CTCAE 5.0. •Patient experience/satisfaction questionnaire with SC isatuximab using the patient experience and satisfaction questionnaire ;Timepoint(s) of evaluation of this end point: For some points, this will be done throughout the study or until the patient dies For other points, this will be done at 12 and 24 months | — |
Countries
France
Contacts
Public ContactFanny ABRIAT
CHU de Poitiers
Outcome results
None listed