The trial aims to demonstrate the non-inferiority of subcutaneous to intravenous isatuximab administration in transplant-eligible patients with newly diagnosed multiple myeloma.
Prospective, multicentre, randomised, parallel group, open, phase III clinical trial, for patients with confirmed diagnosis of untreated multiple myeloma requiring systemic therapy. Investigational Medicinal Product: Isatuximab, subcutaneous administration via a wearable injector system. Randomization: Patients are randomized in one of 2 study arms (A or B) before induction therapy. Patients randomized in arm A will receive 3 cycles of the monoclonal antibody isatuximab intravenously, combined with RVd regimen (Lenalidomide, Bortezomib, Dexamethasone). Each cycle will last for 42 days. Patients in arm B will receive 3 cycles RVd plus isatuximab subcutaneously. After induction therapy, patients will receive standard intensification (usually cyclophosphamide-based mobilization therapy, stem cell collection and high-dose melphalan followed by autologous stem cell transplantation (HDM/ASCT)). End of study will be after the first HDM/ASCT. There is one primary objective: Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd, with respect to rates of VGPR or better after induction therapy (according to standard International Myeloma Working Group (IMWG) response criteria). Key secondary objectives are: 1. Comparison of patient-reported outcomes (PRO) regarding route of administration of isatuximab (SC vs. IV) on induction therapy as assessed by modified CTSQ (modified 9-item questionnaire). 2. Non-inferiority of rates of MRD negativity (assessed by NGS from BMA; sensitivity 10\^-5) independent of standard IMWG response after induction therapy. The duration of the trial for each patients is expected to be approximately 10 months (induction and intensification treatment).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
514
IV isatuximab will be administered weekly in the first cycle (Cycle 1) on days 1, 8, 15, 22, 29, and biweekly on the 2 subsequent cycles at days 1, 15 and 29, at the dose of 10 mg/kg.
SC isatuximab will be administered on days 1, 8, 15, 22, 29 of cycle 1, and on days 1, 15 and 29 of cycles 2-3, at the dose of 1400 mg
Both arms: 25 mg per os on day 1-14 and d22-35 in induction cycle 1-3
Demonstration of non-inferiority of subcutaneous (SC) isatuximab compared to intravenous (IV) isatuximab, both in combination with RVd.
Rates of VGPR or better (according to standard IMWG response criteria), defined as proportion of patients with at least VGPR after induction therapy (according to standard International Myeloma Working Group (IMWG) response criteria).
Time frame: 18 weeks after start of study treatment
Quality of life compared between Arm A and B.
Comparison of PRO (patient-reported outcome) regarding route of administration of isatuximab (SC vs. IV) on induction therapy as assessed by modified CTSQ (modified 9-item questionnaire)
Time frame: 18 weeks after start of study treatment
Non-inferiority of rates of MRD negativity in Arm B compared to Arm A
Rates of NGS-MRD negativity (sensitivity 10\^-5, from bone marrow aspirate) after induction therapy
Time frame: 18 weeks after start of study treatment
Rates of MRD negativity by NGS and NGF (sensitivity 10^-5, from BMA) independent of standard IMWG response after first HDM/ASCT
defined as proportion of negative patients with the corresponding MRD method (NGS or NGF) at the defined timepoint (after induction therapy or first HDM/ASCT)
Time frame: 18 weeks (timepoint "after induction") or 35 weeks (timepoint "after first HDM/ASCT") after start of study treatment
Rates of best overall response to treatment (BOR)
proportion of patients with BOR (at least PR or better) to treatment until end of study (based on timepoints post induction cycle 2 and 3, prior to HDM/ASCT and post first HDM/ASCT)
Time frame: Depending on the timepoint of best response out of all response assessments, up to 10 months from randomization
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Both arms: 1.3 mg/m\^2 subcutaneous on day 1, 4, 8, 11, 22, 25, 29 32 in 3 induction cycles
20 mg per os on day 1-2, 4-5, 8-9, 11-12, 15; and 22-23, 25-26, 29-30, 32-33 in induction cycles 1-3.
Universitätsklinikum Krems
Krems, Austria
Ordensklinikum Linz
Linz, Austria
Landeskrankenhaus Feldkirch-Rankweil
Rankweil, Austria
Universitätsklinikum der Paracelsus, 3. Med. Abteilung/Onkologie Ambulanz
Salzburg, Austria
Universitätsklinikum St. Pölten - Lilienfeld
Sankt Pölten, Austria
Phyrn-Eisenwurzen Klinikum Steyr
Steyr, Austria
Klinik Ottakring
Vienna, Austria
Klinikum Wels-Grieskirchen
Wels, Austria
Uniklinik RWTH Aachen, Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation
Aachen, Germany
Asklepios Kliniken Hamburg GmbH
Altona, Germany
...and 81 more locations
Progression-free survival (PFS)
Time from randomization (at study inclusion) to progression or death from any cause whichever occurs first
Time frame: Until EOS (28 months after start of study)