Expanded Cord Blood Transplant for Multiple Myeloma

Not currently recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for treating multiple myeloma, a challenging blood cancer. It uses expanded cord blood enriched with ECT-001 (UM171) to potentially improve outcomes and reduce side effects, such as chronic graft-versus-host disease, where donor immune cells attack the recipient's body. Suitable participants are those newly diagnosed with high-risk multiple myeloma who have tried certain treatments but still have measurable disease. The trial aims to determine if this new treatment is safe and effective for these patients. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 prior data suggests that this expanded cord blood transplant is safe for multiple myeloma patients?

Research has shown that using ECT-001 (UM171) expanded cord blood for stem cell transplants is promising in terms of safety. In a study with 22 patients, this treatment proved to be safe and practical, as it was generally well-tolerated by recipients. One major benefit is that this method appears to lower the risk of chronic graft-versus-host disease (GVHD), a common issue where donor cells attack the recipient's body.

The treatment involves growing more cord blood cells, which aids in finding better-matched cells for the transplant. Better matches can reduce complications and improve recovery. The study also found that the expanded cord blood has a different mix of cells, including more that support the immune system, potentially reducing GVHD and enhancing immune recovery.

Although this treatment remains in the early stages of testing, the results so far suggest it could be a safer option compared to traditional methods. However, like any medical treatment, risks are involved, so discussing these with a healthcare provider is important if considering joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Unlike the standard treatments for multiple myeloma, which often include chemotherapy, targeted therapy, or stem cell transplants, ECT-001 (UM171) expanded cord blood offers a unique approach. This treatment takes cord blood, expands the number of stem cells using a special compound called UM171, and then transplants them into the patient. This method aims to improve the success rate and reduce the risks associated with traditional stem cell transplants. Researchers are particularly excited because this could mean a more available, potentially safer option for patients who aren’t candidates for conventional transplants.

What evidence suggests that ECT-001 expanded cord blood is effective for multiple myeloma?

Research has shown that using ECT-001 (UM171) expanded cord blood to treat multiple myeloma (MM) appears promising. In this trial, participants will receive ECT-001 (UM171) expanded cord blood transplants. Studies have found that this approach can lower the risk of chronic graft-versus-host disease (GVHD), a common transplant issue. Early results indicate that patients receiving this treatment experience better outcomes, particularly those with high-risk multiple myeloma. The expansion process increases the number of stem cells, improving the match between the donor's cord blood and patients, potentially strengthening the immune system. Although researchers are still studying this treatment, early results are positive and suggest it could be a practical and effective option for high-risk MM patients. ^{1 2 3 5 6}

Who Is on the Research Team?

Jean Roy, MD

Principal Investigator

Ciusss de L'Est de l'Île de Montréal

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. astctjournal.org astctjournal.org/article/S2666-6367(24)00724-3/fulltext

A Pilot Study of UM171-Expanded Cord Blood Grafts for ... Incidence of chronic GVHD was very low after UM171-expanded grafts. •. Myeloma patients with no residual disease after cord blood transplant ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03441958

NCT03441958 | ECT-001 (UM171) Expanded Cord Blood ... This is a single institution, prospective, phase I/II open-label study in a maximum of 20 patients evaluating a novel treatment strategy in NDMM patients with ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39419177/

A Pilot Study of UM171-Expanded Cord Blood Grafts for ... Multiple myeloma (MM) remains associated with a poor outcome, particularly in patients with advanced disease and high-risk (HR) cytogenetics.

4. gvhdhub.com gvhdhub.com/medical-information/um171-expanded-cord-blood-transplantation-for-patients-with-high-risk-ndmm-results-from-a-phase-iii-trial

UM171-expanded cord blood transplantation for patients ... These results indicate that UM171-expanded CB transplantation is a feasible option in patients with high-risk and ultra-high-risk NDMM, showing ...

5. ash.confex.com ash.confex.com/ash/2023/webprogram/Paper173727.html

Paper: UM171 Expanded Cord Blood Transplantation ... Conclusions: This registry matched case-control analysis demonstrated real-word evidence suggesting UM171-expanded CBT recipients have improved ...

6. ctv.veeva.com ctv.veeva.com/study/ect-001-um171-expanded-cord-blood-transplant-to-treat-high-risk-multiple-myeloma

ECT-001 (UM171) Expanded Cord Blood Transplant to Treat ... Multiple Myeloma (MM) is a morbid disease associated with a poor outcome and while current therapies with new drugs have improved survival ...