NCT05804032

Lenalidomide, Bortezomib and Dexamethasone Induction Therapy With Either Intravenous or Subcutaneous Isatuximab in Patients With Newly Diagnosed Multiple Myeloma

A Randomized Phase III Non-inferiority Trial Assessing Lenalidomide, Bortezomib and Dexamethasone Induction Therapy With Either Intravenous or Subcutaneous Isatuximab in Transplant-eligible Patients With Newly Diagnosed Multiple Myeloma.

• Status: Completed
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 514 (actual)
• Sponsor: University of Heidelberg Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

The trial aims to demonstrate the non-inferiority of subcutaneous to intravenous isatuximab administration in transplant-eligible patients with newly diagnosed multiple myeloma.

Detailed description

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).

Conditions

• Multiple Myeloma

Interventions

Type	Name	Description
DRUG	Isatuximab	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.
DRUG	Isatuximab	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
DRUG	Lenalidomide	Both arms: 25 mg per os on day 1-14 and d22-35 in induction cycle 1-3
DRUG	Bortezomib	Both arms: 1.3 mg/m\^2 subcutaneous on day 1, 4, 8, 11, 22, 25, 29 32 in 3 induction cycles
DRUG	Dexamethasone	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.

Timeline

• Start date: 2023-04-14
• Primary completion: 2026-01-30
• Completion: 2026-01-30
• First posted: 2023-04-07
• Last updated: 2026-02-18

Locations

91 sites across 2 countries: Austria, Germany