ECT-001 (UM171) Expanded Cord Blood Transplant to Treat High-risk Multiple Myeloma

Summary

Multiple Myeloma (MM) is a morbid disease associated with a poor outcome and while current therapies with new drugs have improved survival, MM still remains incurable in most patients. The only potential curative treatment remains allogeneic Hematopoietic stem cell transplant (HSCT), as shown by our cohort of 92 newly diagnosed patients who received a sibling tandem auto-allo (HSCT) with an estimated 10-year progression free survival (PFS) of 43%. However, the high incidences of toxicities including chronic graft-versus-host-disease (GVHD) (up to 79%) and disease progression (up to 49%) impair improvement in cure rate. Using umbilical cord blood (CB) as an alternative source of hematopoietic stem cells (HSC) could be superior biologically because of their increased proliferative capacity, greater number of progeny with longer telomeres and better anti-tumor efficacy in presence of positive residual disease. Moreover, using CB has been shown to decrease incidence of chronic GVHD. However, CBs have the disadvantage of having a limited HSC dose leading to prolonged cytopenia and higher risk of infections. In a first in-human trial using CB expanded with the ECT-001 (UM171) molecule (clinicaltrial.gov # NCT02668315), the median net expansion of HSC was 36 fold, which allows for the selection of better HLA matched CB regardless of their lower HSC dose. Moreover, the ECT-001 expanded CBs have a different cell composition than regular CBs, with more than 25% of dendritic cell precursors. This, combined to better HLA matched CBs, may reduce chronic GVHD incidence and improve immune reconstitution. To date, 22 patients received an ECT-001 expanded CB and the procedure proved to be safe and feasible. In this new trial, the goal is to evaluate the safety and efficacy of ECT-001 expanded CB transplant in high risk MM patients.

Timeline

Start

2018-03-07

Primary completion

2023-10-28

Completion

2025-10-17

Publications

• Roy J, Cohen S, Sauvageau G, Ahmad I, Fournier V, Terra R, Caudrelier P, Thiant S, Thauvette G, Bambace N, Delisle JS, Lachance S, Kiss T, Bernard L, Roy DC, Veilleux O, LeBlanc R. A Pilot Study of UM171-Expanded Cord Blood Grafts for Tandem Auto/Allogeneic Hematopoietic Cell Transplant in High and Ultra-High-Risk Myeloma Patients. Transplant Cell Ther. 2025 Jan;31(1):34.e1-34.e14. doi: 10.1016/j.jtct.2024.10.008. Epub 2024 Oct 16.

Drugs

Indications