Expanded Cord Blood Transplant for Multiple Myeloma

Overseen By Jean Roy, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Ciusss de L'Est de l'Île de Montréal

Must be taking: Bortezomib, Lenalidomide

Disqualifiers: Poor organ function, Uncontrolled infection, Active viral infection, Other malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment ECT-001 (UM171) expanded cord blood for multiple myeloma?

Research shows that cord blood transplants can be a feasible option for multiple myeloma, with some patients achieving long-term survival. Additionally, studies on similar treatments using cord blood-derived cells have shown promising responses in multiple myeloma patients. ^{1 2 3 4 5}

Is UM171-expanded cord blood transplantation safe for humans?

UM171-expanded cord blood transplantation has been shown to be safe in humans, with studies indicating lower rates of severe complications like graft-versus-host disease and non-relapse mortality compared to other transplant methods. These findings suggest that it is generally safe for use in humans. ^{1 6 7 8 9}

What makes the ECT-001 (UM171) expanded cord blood treatment unique for multiple myeloma?

The ECT-001 (UM171) expanded cord blood treatment is unique because it involves ex vivo expansion, which increases the number of stem cells available for transplantation. This approach aims to improve engraftment times and reduce the risk of graft failure compared to traditional cord blood transplants, which often have lower cell doses and delayed engraftment. ^{10 11 12 13 14}

What is the purpose of this trial?

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.

Research Team

Jean Roy, MD

Principal Investigator

Ciusss de L'Est de l'Île de Montréal

Eligibility Criteria

This trial is for adults aged 18-65 with newly diagnosed high-risk multiple myeloma who've had specific initial treatments and responded at least partially. They must have undergone a stem cell transplant using Melphalan, not received more than two transplants or certain maintenance drugs for long, and have a suitable cord blood match.

Inclusion Criteria

I have a cord blood match that meets specific health standards.

I have been newly diagnosed with multiple myeloma with specific genetic features.

I have undergone a stem cell transplant after receiving high-dose Melphalan.

Exclusion Criteria

I have had both autologous and allogeneic stem cell transplants.

My heart, lungs, kidneys, or liver are not working well.

My health severely limits my daily activities or I have several serious health issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive a Bortezomib-based induction treatment for a minimum of 4 cycles

16 weeks

Autologous Stem Cell Transplant (ASCT)

Participants undergo ASCT following Melphalan treatment

2 weeks

Conditioning Regimen

Participants receive a reduced intensity conditioning regimen before allogeneic HSCT

1 week

Allogeneic HSCT with ECT-001 Expanded Cord Blood

Participants receive the ECT-001 expanded cord blood transplant

1 day

Initial Follow-up

Participants are followed weekly for the first 3 months for disease evaluation and adverse events

12 weeks

Weekly visits

Extended Follow-up

Participants are monitored monthly for disease evaluation and adverse events in the absence of GVHD

5 years

Monthly visits

Treatment Details

Interventions

• ECT-001 (UM171) expanded cord blood

Trial Overview The trial tests ECT-001 expanded cord blood transplant's safety and effectiveness in treating high-risk multiple myeloma patients. It aims to improve survival rates by potentially reducing chronic graft-versus-host disease and enhancing immune recovery compared to traditional methods.

Participant Groups

Group I: ECT-001 (UM171) expanded cord blood Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Ciusss de L'Est de l'Île de Montréal

Lead Sponsor

Trials

81

Recruited

6,400+

Centre C3i

Collaborator

Trials

1

Recruited

20+

ExCellThera inc.

Industry Sponsor

Trials

5

Recruited

90+

Centre de Commercialisation en Immunothérapie du Cancer (C3i)

Collaborator

Trials

1

Recruited

20+

Findings from Research

Double-unit cord blood transplantation (CBT) has significantly improved engraftment and reduced transplant-related mortality in adult patients with hematologic malignancies, addressing the limitations of single-unit CBT due to cell dose.

Despite only one unit typically sustaining donor hematopoiesis, double-unit CBT offers insights into transplant biology and may protect against relapse, making it a promising option for a wider range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood transplants: one, two or more units? Avery, S., Barker, JN.[2010]

Tandem autologous-non-myeloablative allogeneic stem cell transplantation (ASCT-NMA SCT) shows comparable outcomes for high-risk multiple myeloma patients to standard-risk patients, with a median progression-free survival of 1166 days versus 1465 days, indicating its potential as an effective treatment option.

However, higher doses of CD3+ cells during the procedure are linked to increased risks of acute and chronic graft-versus-host disease (GvHD), higher transplant-related mortality, and poorer overall survival, suggesting careful consideration of CD3+ cell dosing is crucial for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma. Nair, AP., Walker, P., Kalff, A., et al.[2022]

In a study involving 101 patients, umbilical cord blood (UCB) transplantation using expanded CD34+ stem cells significantly improved 100-day survival rates (84.2%) compared to double-unit cord blood transplantation (DUCBT) (74.6%).

The carlecortemcel-L group also experienced faster engraftment of neutrophils and platelets, indicating enhanced recovery post-transplant, while rates of graft-versus-host disease were similar between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cohort-Controlled Comparison of Umbilical Cord Blood Transplantation Using Carlecortemcel-L, a Single Progenitor-Enriched Cord Blood, to Double Cord Blood Unit Transplantation. Stiff, PJ., Montesinos, P., Peled, T., et al.[2019]

In a study involving 137 patients, UM171-expanded cord blood transplants showed lower nonrelapse mortality (NRM) and improved progression-free survival (PFS) and graft-versus-host disease-free relapse-free survival (GRFS) compared to unmanipulated cord blood transplants.

When compared to matched-unrelated donor (MUD) transplants, UM171 recipients had significantly lower NRM and experienced less severe acute and chronic graft-versus-host disease, indicating a safer and more effective option for patients undergoing transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved outcomes of UM171-expanded cord blood transplantation compared with other graft sources: real-world evidence. Cohen, S., Bambace, N., Ahmad, I., et al.[2023]

The study demonstrated that UM171 can successfully expand cord blood stem cells, allowing for the use of smaller single cord blood units without compromising engraftment in patients with hematological malignancies, with a 96% success rate in expansion.

The safety profile was acceptable, with no unexpected adverse events, although there were common complications like febrile neutropenia and one treatment-related death, indicating that while promising, further investigation in randomized trials is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1-2 safety and feasibility study. Cohen, S., Roy, J., Lachance, S., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Phase I study of cord blood-derived natural killer cells combined with autologous stem cell transplantation in multiple myeloma. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Cord Blood Transplantation for Multiple Myeloma: A Study from the Multiple Myeloma Working Group of the Japan Society for Hematopoietic Cell Transplantation. [2015]

3. United States pubmed.ncbi.nlm.nih.gov

Cord blood transplants: one, two or more units? [2010]

4. England pubmed.ncbi.nlm.nih.gov

Autografting followed by a reduced-intensity conditioning unrelated donor cord blood transplantation for a patient with refractory multiple myeloma: successful engraftment with minimal toxicity. [2005]

5. England pubmed.ncbi.nlm.nih.gov

Adverse impact of high donor CD3+ cell dose on outcome following tandem auto-NMA allogeneic transplantation for high-risk myeloma. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Cohort-Controlled Comparison of Umbilical Cord Blood Transplantation Using Carlecortemcel-L, a Single Progenitor-Enriched Cord Blood, to Double Cord Blood Unit Transplantation. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Antigen presenting cell-mediated expansion of human umbilical cord blood yields log-scale expansion of natural killer cells with anti-myeloma activity. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Improved outcomes of UM171-expanded cord blood transplantation compared with other graft sources: real-world evidence. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1-2 safety and feasibility study. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Preclinical ex vivo expansion of cord blood hematopoietic stem and progenitor cells: duration of culture; the media, serum supplements, and growth factors used; and engraftment in NOD/SCID mice. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Ex vivo expansion of cord blood mononuclear cells on mesenchymal stem cells. [2018]

12. England pubmed.ncbi.nlm.nih.gov

Ex vivo expansion of umbilical cord blood. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

Transplantation of ex vivo expanded cord blood. [2019]

14. Korea (South) pubmed.ncbi.nlm.nih.gov

Ex vivo expansion and clonality of CD34+ selected cells from bone marrow and cord blood in a serum-free media. [2006]