Multicenter Open Label Phase 3 Study of Isatuximab Plus Lenalidomide and Dexamethasone With/Without Bortezomib in the Treatment of Newly Diagnosed Non Frail Transplant Ineligible Multiple Myeloma Elderly Patients (≥ 65; < 80 Years).

Summary

Overall the issue of patients above 65-70 years of age being that it is impossible for most of them to undergo an intensive treatment like autologous stem cell transplant with little prospect of debulking effectively the bone marrow with chemotherapy, and also few possibilities to harass the bone microenvironment in the tumoral niche.

If, advanced age in frail patients is predictive of an increased risk of treatment-related toxicity, there is a growing number of elderly patients in regards to transplantation, but still fit if one considers the objectives of life characterized with prolonged survival. These patients might have the same treatment as to the transplant eligible, but without the transplant procedure. The development of immunotherapy has transformed the treatment landscape of cancer, particularly in MM, increasing the treatment possibilities with possibly fewer adverse events.

The therapeutic strategy and treatment options for NTE patients moved from melphalan-based induction regimens to lenalidomide-based associations, which is now the backbone of most treatment for NTE patients. Even though the latest melphalan, bortezomib and prednisone (MPV) association was considered somewhat effective it was not so well tolerated. Furthermore, MPV hardly prolonged PFS beyond 2 years. It was recently improved with the addition of Daratumumab, first in class anti CD38 Mab in the phase III ALCYONE.

The association lenalidomide and dexamethasone (Rd) has significantly improved the easiness of treating the NTE population and all drugs seem to be possible to combine to Rd. In that extent, proteasome inhibitors have always been one of the most impactful family of agents in MM, and as expected Bortezomib plus Rd has become a very relevant and commonly used regimen in NTE NDMM. These groundbreaking results have favored the development of 2 randomized phase 3 studies for registration of combination of antiCD38Mab (Daratumumab (Cepheus, NCT03652064), Isatuximab (Imroz, NCT03319667) +Rd +Velcade in comparison to VRd. Both studies have used as a comparator the VRd regimen which is today one of the safest, active and popular triplet based Rd regimen, approved, and therefore the best control arm possibly for these studies.

However, as much as there has been no direct head to head comparison of VRd to Dara Rd, when looking at the data from Maia it is anticipated that DRd will become a standard of care, and might challenge strongly VRd. Yet, multiple questions remain still, anticipating the change in backbone from VRd to antiCD38 +Rd becoming the new standard of care for NTE NDMM patients. The investigators have therefore planned to answer the critical question of the role of proteasome inhibitors in NTE non frail NDMM when considering anti CD38 +Rd as the backbone.

Conditions

• Multiple Myeloma
• Myeloma

Interventions

DRUG

Isatuximab

Isatuximab by IV route, per 28 days cycle - Cycle1: 10 mg/kg on days 1, 8, 15, and 22. Cycles 2 to 12: 10 mg/kg on days 1 and 15. From cycle 13: 10 mg/kg on day 1.

DRUG

Lenalidomide

Lenalidomide by oral route, per 28 days cycle - 25 mg daily on days 1-21.

DRUG

Bortezomib

Bortezomib sub-cutaneous, per 28 days cycle - Cycles 1 to 12: 1.3 mg/m2 on days 1, 8, 15. Cycles 13-18: 1.3 mg/m2 on days 1, 15.

DRUG

Dexamethasone

Dexamethasone by oral route, per 28 days cycle - 20 mg daily on days 1, 8, 15 and 22.

Sponsors & Collaborators

• Intergroupe Francophone du Myelome

  collaborator NETWORK

• Sanofi

  collaborator INDUSTRY

• Poitiers University Hospital

  lead OTHER

Principal Investigators

• LELEU Xavier, Prof. · Poitiers University Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

65 Years

Max Age

79 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-07-17

Primary Completion

2024-06-18

Completion

2027-08-17

Countries

• France

Study Locations