Newly diagnosed multiple myeloma. MedDRA version: 21.0 Level: LLT Classification code 10028228 Term: Multiple myeloma System Organ Class: 100000004864
Conditions
Interventions
Product Name: Isatuximab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Isatuximab
Other descriptive name: SAR650984 - isatuximab
Concentration unit: mg/ml milligram(s
Sponsors
Cancer Trials Ireland
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Previously diagnosed with MM based on standard IMWG criteria and currently requires treatment. 2. Provided voluntary written informed consent before performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care. 3. Age =18 years, = 75 years, with patients over the age of 70 requiring PI approval. 4. Measurable disease defined as at least one of the following: • Serum M protein = 0.5 g/dL (=5 g/L) • Urine M protein =200 mg/24 hours • Serum free light chain (FLC) assay: Involved FLC assay =10 mg/dL (=100 mg/L) and an abnormal Serum FLC ratio (1.65) 5. Screening Laboratory evaluations within the following parameters: • Absolute neutrophil count (ANC) = 1,000 cells/dL (1.0 x 10^9/L) (Growth factors cannot be used within 14 days before first drug administration) • Platelet count = 75,000 cells/dL (75 x 10^9/L) if =65 years) yes F.1.3.1 Number of subjects for this age range 21
Exclusion criteria
Exclusion criteria: 1. Prior therapy for multiple myeloma. Participants who received smouldering treatment qualify to participate as long as the prior treatment was not a CD38 therapy. 2. Diagnosed or treated for another malignancy within 3 years prior to enrolment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low risk prostate cancer after curative therapy. 3. Central nervous system involvement. 4. Peripheral neuropathy = Grade 3, or Grade 2 with pain on clinical examination during the screening period. 5. Any medical or psychiatric illness that in the Investigator’s opinion, would impose excessive risk to the patient or would adversely affect his/her participating in this study. 6. Concurrent uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, Grade 3 thromboembolic event or myocardial infarction within the past 6 months. 7. Prior major surgical procedure or radiation therapy within 4 weeks of initiation of therapy (this does not include limited course of radiation used for management of bone pain within 7 days of initiation of therapy). 8. Daily requirement for corticosteroids (equivalent to > 10 mg/day prednisone for more than 7 days (except for inhalation corticosteroids). Patients may receive corticosteroids for the management of their MM that should not exceed the equivalent of 160mg of dexamethasone in a 2-week period and should be stable for at least 7 days prior to the initiation of study treatment. 9. Concurrent symptomatic amyloidosis or plasma cell leukaemia 10. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) 11. Known active infection requiring parenteral or oral anti-infective treatment within 14 days of start of therapy. 12. Active hepatitis B or hepatitis C viral infection 13. Pregnant or breastfeeding female or female who intends to become pregnant during the participation in the study. Females of childbearing potential (FCBP) unwilling to prevent pregnancy by the use of a highly effective method of contraception for =4 weeks before the start of study treatment, during treatment (including dose interruptions), and up to 5 months following the last dose of study treatment and/or who are unwilling or unable to be tested for pregnancy before study treatment initiation (2 negative tests), weekly during 1st month of treatment and then prior each treatment cycle administration or every 2 weeks in case or irregular menstrual cycles up to 5 months following the last dose of study treatment. 14. Male participants who disagree to practice true abstinence or disagree to use highly effective contraception during sexual contact with a pregnant female or a FCBP while participating in the study during dose interruptions and at least 5 months following study treatment discontinuation, even if he has undergone a successful vasectomy. Note 1: a FCBP is a female who: 1) has achieved menarche at some time point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months). Note 2: True abstinence is acceptable when this is in line with the prefe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the VGPR or better rate at the end of two cycles of induction treatment, defined as the proportion of patients who have achieved VGPR or better, according to IMWG criteria (Kumar et al. 2016), at the end of two cycles of induction treatment.;Secondary Objective: To evaluate Complete Response (CR) and sCR rate following one year and two years of maintenance therapy. • To evaluate overall response rate (ORR) and rate of VGPR, or better, following one year of maintenance therapy. ORR will be defined as achieving a partial response or better. • To evaluate time to VGPR or better. • To assess negative minimal residual disease (MRD) rate following induction, following ASCT and after 1 and 2 years of maintenance treatment. • To evaluate clinical outcomes including: o Time to progression (TTP) o Progression-free survival (PFS) o OS o Duration of response (DOR) • To assess the safety and tolerability of Isa-RVD. • To evaluate stem cell yield after mobilization. Note: Please refer to trial protocol for exploratory objectives and correlative objectives. ;Primary end point(s): VGPR or better rate at the end of two cycles of induction treatment, defined as the proportion of patients who have achieved VGPR or better, according IMWG criteria (Kumar et al. 2016), at the end of two cycles of induction treatment. ;Timepoint(s) of evaluation of this end point: The primary analysis will be performed on the response data after two cycles for all evaluable patients in the Full Analysis Set. All efficacy analyses will be performed for the Full Analysis Set, which is the set of all eligible patients who start study medication and have some post-baseline assessment of efficacy. Safety analyses will be performed for the Safety Data Set, which is the set of all patients excluding those who received no study medication. After the study has been completed, the data cleaned, and the database closed out, the statistical analysis will be performed by Cancer Trials | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • CR and sCR rate after one year and two years of maintenance therapy. • ORR and rate of VGPR or better following one year of maintenance therapy. ORR will be defined as achieving a partial response or better. • Time to VGPR or better. • Negative MRD rate following induction, ASCT and after 1 and 2 years of maintenance treatment. • Clinical outcomes including: o TTP o PFS o OS o DOR • Safety and tolerability of Isa-RVD. • Stem cell yield after mobilization.;Timepoint(s) of evaluation of this end point: The primary analysis will be performed on the response data after two cycles for all evaluable patients in the Full Analysis Set. All efficacy analyses will be performed for the Full Analysis Set, which is the set of all eligible patients who start study medication and have some post-baseline assessment of efficacy. Safety analyses will be performed for the Safety Data Set, which is the set of all patients excluding those who received no study medication. After the study has been completed, the data cleaned, and the database closed out, the statistical analysis will be performed by Cancer Trials Ireland according to the Statistical Analysis Plan. | — |
Countries
Denmark, Ireland, United Kingdom
Contacts
Public ContactHead of Clinical Operations
Cancer Trials Ireland
Outcome results
None listed