ISATUXIMAB for Multiple myeloma|Newly diagnosed transplant ineligible multiple myeloma

Inclusion criteria

• {"criterion_text":"-Must be able to understand and voluntarily sign an informed consent form\n-Adequate organ function documented within one week prior to the first intake of investigational product (C1J1) defined as: -Serum total bilirubin < 2x upper limit of normal (ULN), -Creatinine clearance ≥ 30ml/min calculated with MDRD formula, -Serum SGOT/AST or SGPT/ALT < 3x upper limit of normal (ULN).\n-Person affiliated to the French social security system or equivalent\n-A man who is sexually active with a pregnant woman or a woman of childbearing potential must agree to use a barrier method of birth control\te.g.,\tcondom with\tspermicidal foam/gel/film/cream/suppository during the study and for at least 5 months after the last dose of treatment, even he has had a vasectomy.\n-A female participant is eligible to participate ifSsahiesiiss sneozt pdruegtneaxntet, not breastfeeding, and at least one of the following conditions applies: 1.\tNot a female of childbearing potential Or /2.A FCBP* who must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 – 14 days prior to and again within 24 hours prior to starting study medication and before each cycle of study treatment. A FCBP* must understand and agree to continue abstinence from heterosexual intercourse or to use 2 reliable effective methods of contraception (a very effective method and an effective additional method) simultaneously without interruption: 2.1.\tFor at least 28 days before starting experimental treatments, 2.2.Throughout\tthe\tentire\tduration\tof\texperimental treatments, 2.3.During dose interruptions, 2.4.And for at least 5 months after the last dose of experimental treatments.\n-All patients must understand and accept to comply with the conditions of the Lenalidomide pregnancy prevention plan\n-Must be able to adhere to the study visit schedule and other protocol requirements\n-Patient able to swallow the various oral treatments\n-Life expectancy > 6 months\n-Subject, male or female, must be at least ≥ 65 years of age\n-Must have a Newly diagnosed Multiple Myeloma requiring therapy (SLiM CRAB criteria)/1.Monoclonal plasma cells in the bone marrow ≥ 10% or presence of a biopsy proven plasmacytoma /2.Revised International Myeloma Working Group diagnostic criteria for multiple myeloma Myeloma defining events: -\tEvidence 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) -Anemia: hemoglobin value of ≥ 20 g/L below the lower limit of normal, or hemoglobin value ≤ 100 g/L-Bone lesions: one or more osteolytic lesions on skeletal radiography, CT, or PET-CT -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 •>1 focal lesion on MRI studies (Each focal lesion must be 5 mm or more in size.)\n-Must have measurable disease as defined by any of the following: -Serum monoclonal paraprotein (M-protein) level ≥5 g/L or -\turine M- protein level ≥200 mg/24 hours; or -Serum immunoglobulin free light chain ≥100 mg/L and abnormal serum immunoglobulin kappa lambda free light chain ratio (any method)\n-Must be nontransplant eligible 1.\tNewly diagnosed and not considered candidate for high- dose chemotherapy with SCT. 2.ECOG ≤2\n-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: -Absolute neutrophils ≥ 1 x109/L, -\tUntransfused Platelet count ≥ 75 x109/L, -\tHemoglobin ≥8.5 g/dL."}

Exclusion criteria

• {"criterion_text":"-Subject has a diagnosis of primary systemic amyloidosis, monoclonal gammopathy of undetermined significance, or smouldering multiple myeloma\n-Known to have hepatitis C active infection (positive HCV RNA and negative anti-HCV)\n-Subject has any clinically significant medical or psychiatric condition or disease (e.g., uncontrolled diabetes, acute diffuse infiltrative pulmonary disease) in the investigator’s opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results.\n-Subject has active systemic infection and severe infections requiring treatment with a parenteral administration of antibiotics.\n-Subject has clinically significant cardiac disease, including: •\tmyocardial infarction within 6 months before study treatment, or an unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina, congestive heart failure, New York Heart Association Class III-IV) •uncontrolled cardiac arrhythmia (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 5 Grade ≥2) or clinically significant ECG abnormalities or LVEF < 40 %\n-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\n-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\n-Acute diffuse infiltrative pneumopathy, pericardial disease\n-Subject has plasma cell leukemia (according to World Health Organization [WHO] criterion: ≥20% of cells in the peripheral blood with an absolute plasma cell count of more than 2X 109/L) or POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).\n-Subject is known or suspected of not being able to comply with the study protocol (e.g., because of alcoholism, drug dependency, or psychological disorder). Subject has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol- specified assessments. Subject is taking any prohibited medications.\n-Subject has had major surgery within 2 weeks before study treatment or has not fully recovered from surgery, excluding surgery related to myeloma\n-Subject has a diagnosis of Waldenström’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.\n-Subject has received an investigational drug (including investigational vaccines) within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer, or used an invasive investigational medical device within 4 weeks before study treatment or is currently enrolled in an interventional investigational study.\n-Persons referred to in Articles L1121-5 to L1121-8 of the CSP\n-Refusal to consent or protected by a legal regime (safeguard of justice, curatorship, guardianship).\n-Subject has contraindications to required prophylaxis for deep vein thrombosis and pulmonary embolism\n-Incidence of gastrointestinal disease that may significantly alter the absorption of oral drugs.\n-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\n-Subject has a history of ongoing malignancy (other than multiple myeloma) within 3 years (date of diagnosis of the malignancy) before inclusion in the study treatment (exceptions are malignancies considered cured with minimal risk of recurrence within 3 years, even though the patient receives treatment).\n-Subject has had radiation therapy within 7 days study treatment unless done for antalgic reason or in case of functional risk for the patient\n-Subject has had plasmapheresis within 7 days study treatment unless patient disease is still measurable (inclusion criteria n°6) after the plasmapheresis\n-Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma\n-Known to be seropositive for history of human immunodeficiency virus (HIV).\n-Known to have hepatitis B active or uncontrolled infection (positive HBsAg and/or HBV DNA)"}

Primary endpoints

• {"endpoint_text":"-very good partial response rate (VGPR) will be assessed according to IMWG international criteria*","definition_or_measurement_approach":"VGPR assessed according to IMWG international criteria"}

Secondary endpoints

• {"endpoint_text":"-To determine Survivals, Overall Survival (OS), Progression free survival (PFS), Time to Progression (TTP), Time to Next Therapy (TTNT) and Event Free survival (EFS)","definition_or_measurement_approach":"Survival endpoints including OS, PFS, TTP, TTNT, EFS (standard definitions as listed)"}
• {"endpoint_text":"-To determine duration of response (DOR) and time to response (TTR)","definition_or_measurement_approach":"DOR and TTR measured per protocol"}
• {"endpoint_text":"-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.","definition_or_measurement_approach":"Response assessed per IMWG criteria; ORR, PR, CR and MRD 10^-5 with sustained assessments at 12 and 24 months"}
• {"endpoint_text":"-To assess the safety, including infusions reactions, device deficiencies, and local tolerability (injections site reactions) of SC isatuximab + VRd according to CTCAE 5.0.","definition_or_measurement_approach":"Safety assessed using CTCAE v5.0; includes infusion reactions, device deficiencies, injection site reactions"}
• {"endpoint_text":"-Patient experience/satisfaction questionnaire with SC isatuximab using the patient experience and satisfaction questionnaire","definition_or_measurement_approach":"Patient-reported experience/satisfaction measured via specified questionnaire"}
• {"endpoint_text":"-To assess of abilities and life quality of patients QLQ-C30, QLQ-MY20 and EQ-5D-5L","definition_or_measurement_approach":"Quality of life assessed using QLQ-C30, QLQ-MY20 and EQ-5D-5L instruments"}
• {"endpoint_text":"-FOR MIBAPIX AND PK-ADA•To estimate isatuximab PK parameters and derived exposure by population PK modelling","definition_or_measurement_approach":"Population PK modelling to estimate isatuximab PK parameters and exposure"}
• {"endpoint_text":"-FOR MIBAPIX AND PK-ADA•\tIncidence of participants with anti-drug antibodies (ADA) against isatuximab","definition_or_measurement_approach":"Incidence of anti-drug antibodies measured by ADA assays"}
• {"endpoint_text":"-FOR MIBAPIX AND PK-ADA•\tTo determine apixaban plasma exposure with the area under the concentration curve in relation to time","definition_or_measurement_approach":"Apixaban exposure assessed by AUC (area under the concentration-time curve)"}

France

Earliest CTIS Part Ii Submission Date

14-10-2024

Latest Decision Or Authorization Date

18-02-2026

Processing Time Days

492

Number Of Sites

29

Number Of Participants

74

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Poitiers

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Laboratoire SANOFI","duties_or_roles":"Source of monetary support","organisation_type":""}
• {"country":"","full_name":"CHU de Poitiers","duties_or_roles":"Source of monetary support","organisation_type":""}