Patients with multiple myeloma, newly diagnosed and eligible for autologous stem cell transplantation MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: SARCLISA
Product Name: Isatuximab
Product Code: SAR650984
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Isatuximab
Concentration unit: mg/ml milligram(s)
Sponsors
Intergroupe Francophone du Myélome
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female subjects, 18 years of age or older, younger than 66 years ( 0.25 mmol/L (> 1 mg/dL) higher than ULN or > 2.75 mmol/L (> 11 mg/dL) - Renal insufficiency: creatinine clearance 177 µmol/L (> 2 mg/dL) - Anemia: hemoglobin > 2 g/dL below the lower limit of normal or hemoglobin 50 Giga/l (transfusions are not permitted to achieve this minimum platelet count). 7) Women of childbearing potential must have a negative serum or urine pregnancy test within 10 to 14 days prior to therapy and repeated within 24 hours before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (One highly effective method and one additional effective method) used at the same time, beginning at least 4 weeks before initiation of lenalidomide treatment and continuing for at least 30 days after the last dose of Lenalidomide, Iberdomide and 5 months after last dose of Isatuximab. Women must also agree to notify pregnancy during the study. 8) Men must agree to not father a child and agree to use a latex condom during therapy and for and during dose interruptions and for at least 90 days after the last dose of study drug including Lenalidomide and Iberdomide and 5 months after last dose of Isatuximab, even if they have had a successful vasectomy, if their partner is of childbearing potential. Patient must also refrain from donating sperm during this pe
Exclusion criteria
Exclusion criteria: -Subjects must not have been treated previously with any systemic therapy for multiple myeloma. Prior treatment with corticosteroids or radiation therapy does not disqualify the subject (the maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone in a 2-week period). Two weeks must have elapsed since the date of the last radiotherapy treatment. Enrolment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy -Subject has a diagnosis of primary amyloidosis, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma, or solitary plasmacytoma. 3) Subject has a diagnosis of Waldenström’s macroglobulinemia, or other conditions in which IgM M-protein is present in the absence of a clonal plasma cell infiltration with lytic bone lesions. 4) Subject has had plasmapheresis within 14 days of C1D1. 5) Subject is exhibiting clinical signs of meningeal involvement of multiple myeloma. 6) Myocardial infarction within 4 months prior to enrolment according to NYHA Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities 7) Uncontrolled hypertension 8) Subjects with a history of moderate or severe persistent asthma within the past 2 years, or with uncontrolled asthma of any classification at the time of screening (Note that subjects who currently have controlled intermittent asthma or controlled mild persistent asthma are allowed in the study). 9) Intolerance to hydration due to pre-existing pulmonary or cardiac impairment. 10) 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). 11) Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results. 12) Systemic treatment with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John’s wort within 14 days before the first dose of study treatment. 13) Known intolerance to steroid therapy, mannitol, pregelatinized starch, odium 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. 14) History of allergy to any of the study medications, their analogues, or excipients in the various formulations 15) Subject has had major surgery within 2 weeks before study inclusion (informed consent signature) or will not have fully recovered from surgery, or has surgery planned during the time the subject is expected to participate in the study. Kyphoplasty or Vertebroplasty are not considered major surgery. 16) Clinically relevant active infection or seri
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints • Sustained MRD rate at year 2, 3, 4 post inclusion will be analyzed similarly to the primary endpoint. • For Overall Survival (OS), the distribution of OS since randomization will be estimated using Kaplan Meier method. The comparison of the 2 arms will be made by log-rank test. Treatment effect will be described by Hazard Ratio and its 2-sided 95% confidence intervals are will be estimated using a Cox regression model adjusted on stratification variables (with high risk cytogenetics and MRD negative rate (10-5 NGS) after induction as fixed effects and center as random effects for A vs B comparison, and high risk cytogenetics as fixed effects and center as random effects for C vs D comparison). • Progression Free survival, defined as time from randomization to either progression or death will be analyzed similarly. ;Timepoint(s) of evaluation of this end point: end of induction phase end of consolidation phase end of maintenance phase end of the study | — |
Primary
| Measure | Time frame |
|---|---|
| Main Objective: For patients MRD negative after induction (NGS, 10-5) Principal objective: increase by 15% the rate of MRD negativity (NGS, 10-6) before maintenance with high-dose therapy and ASCT (Arm B) vs additional cycles of Isa-KRD (Arm A), i.e., 85% MRD negativity in Arm B vs 70% in Arm A. Secondary objectives: MRD post consolidation, responses rate according to IMWG criteria, PFS , OS, safety (ongoing basis), sustained MRD negativity (every year since the start of maintenance phase). For patients MRD positive after induction (NGS, 10-5) Principal objective: increase by 20% the rate of MRD negativity (NGS, 10-6) before maintenance with tandem ASCT (Arm D) vs single ASCT (Arm C), i.e., 45% MRD negativity in Arm D vs 25% in Arm C. Secondary objectives: MRD post consolidation, responses rate according to IMWG criteria, PFS, OS, safety (ongoing basis), sustained MRD negativity (every year since the start of maintenance phase), PRO for arms C&D (every year since the start of maintenance) ;Secondary Objective: PFS , OS, sustained MRD negativity and safety .;Primary end point(s): For both parts of the trial (A vs B and C vs D), the primary comparison of the 2 strategies will be made with respect to negative MRD rate (10-6 NGS) before maintenance using the chi square test in the ITT population. The observed MRD negative rate will be provided along with its 2-sided 95% Confidence interval (CI). Treatment effect will be described by an Odds Ratio, along with its 2-sided 95% confidence interval, by fitting a logistic regression model adjusted on stratification variables (with high risk cytogenetics and MRD negative rate (10-5 NGS) after induction as fixed effects and center as random effects for A vs B comparison, and high risk cytogenetics as fixed effects and center as random effects for C vs D comparison). In case of missing MRD, data will be imputed as positive in all arms. Sensitivity analyses will be performed using best-worst and worst-best case to check for | — |
Countries
France
Contacts
Public ContactChanaz Louni
Intergroupe Francophone du Myélome
Outcome results
None listed