ISATUXIMAB for Newly diagnosed multiple myeloma

Inclusion criteria

• {"criterion_text":"- Previously diagnosed with MM based on standard IMWG criteria and currently requires treatment.\n- 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performance of any study-related procedures not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.\n- Age ≥18 years, ≤75 years, with patients over the age of 70 requiring CI approval.\n- Measurable disease defined as at least one of the following: •\tSerum M protein ≥0.5g/dL (≥5g/L) •\tUrine M protein ≥200 mg/24 hours •\tSerum FLC assay: Involved FLC assay ≥10 mg/dL (≥100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65).\n- Screening laboratory evaluations within the following parameters: •\tANC ≥ 1,000 cells/dL (1.0 x 109/L) (growth factors cannot be used within 14 days before first study treatment administration) •\tPlatelet count ≥75,000 cells/dL (75 x 109/L) if <50% BM nucleated cells are plasma cells, ≥30,000 cells/dL (30 x 109/L) if ≥50% of BM nucleated cells are plasma cells (without transfusions required during the 3 days prior to the screening haematologic test) •\tTotal bilirubin ≤2.0 X ULN (except patients with Gilbert Syndrome, who are eligible if total bilirubin <3.0 mg/dL) •\tAST (SGOT) and ALT (SGPT) ≤3.0 x ULN •\tHaemoglobin ≥8g/dL •\tCalculated CrCl ≥30 mL/min.\n- ECOG performance status ≤ 2.\n- Participant agrees to be registered into the mandatory Risk Management Programme for Lenalidomide and be willing and able to comply with the requirements of this programme.\n- Ability to understand and the willingness to sign a written informed consent document.\n- Participant is considered eligible for ASCT by the treating physician."}

Exclusion criteria

• {"criterion_text":"- Prior therapy for multiple myeloma. Participants who received smouldering treatment qualify to participate as long as the prior treatment was not a CD38 therapy.\n- POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes).\n- Known active infection requiring parenteral or oral anti-infective treatment within 7 days of start of study treatment.\n- Active hepatitis B or hepatitis C viral infection.\n- Pregnant or breastfeeding female or female who intends to become pregnant during the participation in the study. 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) and then monthly up to 5 months following the last dose of study treatment.\n- Male participants who disagree to practice true abstinence or disagree to use highly effective contraception during sexual contact with a pregnant female or FCBP while participating in the study during dose interruptions and at least 3 months following study treatment discontinuation, even if he has undergone a successful vasectomy.\n- Receiving any other investigational agents.\n- Hypersensitivity to steroids, or H2 blockers that would prohibit further treatment with these agents.\n- Inability to tolerate thromboprophylaxis.\n- Hypersensitivity (or contraindication) to dexamethasone, sucrose histidine (as base and hydrochloride salt), boron, mannitol, and polysorbate 80, or to any of the components of the study therapy.\n- 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.\n- Central nervous system involvement.\n- Peripheral neuropathy ≥ Grade 3, or Grade 2 with pain on clinical examination during the screening period.\n- 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.\n- Concurrent uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, Grade 3 thromboembolic event or myocardial infarction within 6 months prior to enrolment\n- Prior major surgical procedure or radiation therapy within 4 weeks of initiation of study treatment (this does not include limited course of radiation used for management of bone pain within 7 days of study treatment).\n- 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.\n- Concurrent symptomatic amyloidosis or plasma cell leukaemia."}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Defined as the proportion of patients who have achieved Very Good Partial Response (VGPR) or better according to IMWG criteria (Kumar et al. 2016) at the end of two cycles of induction treatment."}

Secondary endpoints

• {"endpoint_text":"- CR and sCR rate after one year and two years of maintenance therapy.\n- ORR and rate of VGPR or better following one year of maintenance therapy. ORR will be defined as achieving a partial response or better.\n- Time to VGPR or better.\n- Negative MRD rate following induction, ASCT and after 1 and 2 years of maintenance treatment.\n- Clinical outcomes including: TTP, PFS, OS, DOR.\n- Safety and tolerability of Isa-RVD.\n- Stem cell yield after mobilization.\n- CR and sCR rate following induction, ASCT and maintenance treatment in the subgroup of non-IgG kappa positive patients.\n- Duration of and time to sCR and time to CR in the subgroup of non-IgG kappa positive patients.\n- Clinical efficacy in high-risk cytogenetic subgroups: del(1p), gain of 1q, del(17p), t(4;14), t(14;16), t(14;20).\n- Immune profiling (NK, T, and B cells) and T-cell receptor sequencing.\n- MRD detection performed by flow cytometry and NGS.\n- Immunogenicity of Isatuximab.\n- PROs.\n- Stem cell yield after mobilization (number of CD34+ cells)","definition_or_measurement_approach":"ORR defined as achieving a partial response or better. MRD assessed following induction, ASCT and after 1 and 2 years of maintenance (methods include flow cytometry and NGS as specified). Immune profiling and T-cell receptor sequencing as exploratory biomarker assessments. Stem cell yield measured as number of CD34+ cells. Other endpoints are as stated (time-to-event outcomes: TTP, PFS, OS, DOR; safety/tolerability per standard clinical reporting)."}

Ireland

Earliest CTIS Part Ii Submission Date

02-09-2024

Latest Decision Or Authorization Date

03-06-2025

Processing Time Days

274

Number Of Sites

7

Number Of Participants

45

Denmark

Earliest CTIS Part Ii Submission Date

02-09-2024

Latest Decision Or Authorization Date

28-05-2025

Processing Time Days

268

Number Of Sites

1

Number Of Participants

7

Primary sponsor

Full Name

Cancer Trials Ireland

Organisation Type

Patient organisation/association

Country Of Registered Address

Ireland

Contract research organisations

Name

ALMAC Clincial Services (Ireland) Ltd

Responsibilities

IMP Storage and Distribution

Third parties

• {"country":"Denmark","full_name":"GCP-enheden ved Aalborg og Aarhus Universitetshospitaler","duties_or_roles":"","organisation_type":"Health care"}
• {"country":"United Kingdom","full_name":"Sanofi","duties_or_roles":"Providing Isatuximab and funding","organisation_type":"Health care / Sponsor (provider of IMP and funding)"}
• {"country":"Ireland","full_name":"ALMAC Clincial Services (Ireland) Ltd","duties_or_roles":"IMP Storage and Distribution","organisation_type":"Health care / Clinical services"}
• {"country":"United States","full_name":"Ghobrial Lab, Dana Farber Cancer Institute","duties_or_roles":"Sample analysis","organisation_type":"Health care / Research laboratory"}
• {"country":"Ireland","full_name":"Next Generation Sequencing Lab (Mater Misericordiae University Hospital)","duties_or_roles":"Sample storage and analysis","organisation_type":"Health care / Laboratory"}
• {"country":"Ireland","full_name":"Next Generation Sequencing Lab to the Department of Biology, National University of Ireland","duties_or_roles":"Sample analysis","organisation_type":"Health care / Laboratory"}