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

NCT03441958 | Completed Phase 1 DMC

• 1 other identifier: HMR007
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma

Keywords

hematopoietic stem cell transplant; Expanded cord blood

Outcome Measures

Primary Outcomes (6)

• Safety of ECT-001 expanded CB expansion as measured by toxicity evaluation

  AEs with a CTCAE grade ≥ 3 (non hematologic) and with a grade ≥ 4 (hematologic) will be reported from the beginning of the conditioning regimen up to 5 years after CB transplant.

  5 years

• Feasibility of ECT-001 expanded CB expansion

  Number of successful expansion and infusions in an outpatient nonmyeloablative transplant condition for high-risk myeloma patients

  5 years

• Measure of the kinetics of donor lymphoid cells recovery

  Donor lymphocytes cells recovery assessed by chimerism analysis.

  2 years

• Measure of the kinetics of donor myeloid cells recovery

  Time to neutrophils and platelets engraftment will be measured

  2 years

• Incidence of chronic GVHD by grade at 1 years by NIH criteria.

  The incidence of chronic GVHD will be evaluated at 1 years using the recommendations of the NIH Consensus Conference and recently updated. Analysis by cumulative incidence

  1 year

• Incidence of chronic GVHD by grade at 2 years by NIH criteria.

  The incidence of chronic GVHD will be evaluated at 1 years using the recommendations of the NIH Consensus Conference and recently updated. Analysis by cumulative incidence

  2 years

Secondary Outcomes (25)

• Correlation between neutrophil and CD34+ doses infused

  2 years

• Correlation between neutrophil and CD34+CD45RA+ doses infused

  2 years

• Incidence of graft failure

  2 years

• Evaluation of T Cells reconstitution

  3 years

• Evaluation of B cells reconstitution

  3 years

Study Arms (1)

ECT-001 (UM171) expanded cord blood

EXPERIMENTAL

1. Patients will receive a reduced intensity conditioning regimen containing Cyclophosphamide 50 mg/kg, Fludarabine 40 mg/m2 x 5 days and total body irradiation 200 cGy. 2. The cord to be expanded is thawed 7 days prior to transplant and undergoes CD34+ selection. The CD34+ product will be placed in the fed-batch culture with UM171 for a 7-day expansion and is infused fresh on Day 0. The CD34- product is cryopreserved and will be thawed and infused on Day +1. 3. Patients will receive standard supportive care and GVHD prophylaxis with Mycophenolate mofetil and Tacrolimus.

Biological: ECT-001 (UM171) expanded cord blood

Interventions

ECT-001 (UM171) expanded cord blood BIOLOGICAL

ECT-001 expanded cord-blood will be produced and infused on site

ECT-001 (UM171) expanded cord blood

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years.
• Newly diagnosed multiple myeloma using the International Myeloma Working Group criteria with measurable disease and any of the following:
• i. t(4;14), t(14;16), t(14;20), del(17p13), chromosome 1 abnormalities with ISS II or III; ii. Revised-ISS 3; iii. Primary plasma cell leukemia; iv. Refractory to first line triplet Bortezomib-based induction treatment. v. ≥ 2 cytogenetics abnormalities as defined above regardless of ISS stage
• Received a first line triplet Bortezomib-induction regimen for a minimum of 4 cycles with achievement of at least partial response; or received a doublet or triplet Lenalidomide-based second line induction treatment with at least partial response for patients refractory to Bortezomib in first line.
• Received high-dose Melphalan ≥ 140 mg/m2 followed by ASCT.
• Availability of a cord blood with an HLA match ≥ 5/8 and \< 8/8 meeting the following requirements: CD34+ cell count ≥ 0.5 x 105/kg and nucleated cell count \>= 1.5 x 107/kg.

You may not qualify if:

• Having previously received two ASCT.
• Having previously received autologous-allogeneic tandem transplantation.
• Having received more than 4 months of maintenance with Lenalidomide or Bortezomib after ASCT.
• Poor organ function defined as either: forced vital capacity, forced expiratory volume in 1 second or lung diffusing capacity of carbon monoxide corrected for hemoglobin \< 50%, left ventricular ejection fraction \< 40% (evaluated by either echocardiogram or MUGA), uncontrolled arrhythmia or symptomatic cardiac disease, creatinine clearance \< 60 mL/minute.
• Karnofsky score \< 70% or comorbidity index HCT-CI \> 3.
• Bilirubin \> 2 x upper limit of normal (ULN) unless felt to be related to Gilbert's disease or hemolysis; AST and ALT \> 2.5 x ULN; alkaline phosphatase \> 5 x ULN; liver cirrhosis.
• Non secretory disease or non-measurable disease in serum or urine at time of diagnosis.
• Uncontrolled infection.
• Active infection with any of the following viruses: HIV, HTLV-1 or 2, hepatitis B or C.
• Presence of another malignancy with an expected survival estimated \< 75% at 5 years.
• Suspicion of cardiac amyloidosis.
• Current history of drug and/or alcohol abuse.
• Availability of a matched sibling donor.
• Pregnancy, breastfeeding or unwillingness to use appropriate contraception.
• Participation in a trial with an investigational agent within 30 days prior to entry in the study.

Sponsors & Collaborators

• ExCellThera inc.: collaborator
• Centre C3i: collaborator
• Ciusss de L'Est de l'Île de Montréal: lead

Study Sites (1)

CIUSSS de l'Est-de-l'île-de-Montréal, Installation Hôpital Maisonneuve Rosemond

Montreal, Quebec, H1T2M4, Canada

Location

Related Publications (1)

• 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.

  PMID: 39419177 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jean Roy, MD

  Ciusss de L'Est de l'Île de Montréal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 2, 2018
• First Posted: February 22, 2018
• Study Start: March 7, 2018
• Primary Completion: October 28, 2023
• Study Completion: October 17, 2025
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)