Expanded Cord Blood Transplant for Blood Cancers

Not currently recruiting at 2 trial locations

Overseen By Filippo Milano, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ExCellThera inc.

Disqualifiers: HIV, Hepatitis B/C, Liver cirrhosis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new method to improve cord blood transplants for patients with high-risk blood cancers like acute leukemia and myelodysplasia. The treatment uses UM171, a compound that increases the number of stem cells in cord blood, potentially enhancing the transplant's effectiveness. This approach could benefit those who have not succeeded with other treatments. Eligible patients include those who have faced challenges with previous treatments for acute leukemia, such as relapses after a transplant or resistance to chemotherapy. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 to get a clear answer.

What prior data suggests that this cord blood expansion protocol is safe for patients with high risk acute leukemia/myelodysplasia?

Research has shown that the UM171-expanded cord blood transplant is promising in terms of safety. In an earlier study, patients who received this treatment had a low risk of serious complications. Only 5% experienced transplant-related death, and 10% had severe acute graft-versus-host disease, where donor cells attack the patient's body. Notably, there were no cases of moderate to severe chronic graft-versus-host disease.

The study monitored 22 patients for 18 months. These patients had aggressive blood cancers and other serious health issues. Despite these challenges, the treatment proved safe, with 90% of patients surviving for 12 months. These results suggest that the UM171-expanded cord blood transplant is well-tolerated with few serious side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for blood cancers, which often involve traditional chemotherapy or standard cord blood transplants, ECT-001-CB is unique because it enhances cord blood stem cells using a molecule called UM171. This process expands the number of stem cells available for transplant, potentially increasing the success rate and speed of recovery for patients. Researchers are excited about this treatment because it could lead to faster engraftment and reduce complications like graft-versus-host disease, making transplants safer and more effective.

What evidence suggests that the UM171-Expanded Cord Blood Transplant could be an effective treatment for blood cancers?

Research has shown that UM171-expanded cord blood transplants, which participants in this trial will receive, can effectively treat blood cancers. In a previous study, patients who received this treatment had a low risk of dying from the transplant, only 5%, and experienced low rates of severe graft-versus-host disease (GVHD), a complication where the donor's cells attack the patient's body. Impressively, 90% of patients were still alive one year after the transplant, and 74% had no cancer progression. This treatment allows for the use of smaller and better-matched cord blood units, which is important for patients with high-risk blood cancers. Even in patients with hard-to-treat conditions, the cancer progression rate was only 20% at 12 months. Overall, the evidence suggests that UM171-expanded cord blood transplants can improve survival rates and reduce complications. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for patients with high-risk leukemia or myelodysplasia, including those who have failed previous treatments or have advanced disease stages. Participants must be in relatively good physical condition with adequate organ function and not pregnant. They should not have had certain recent transplants, active infections, HIV, other malignancies with poor prognosis, or liver cirrhosis.

Inclusion Criteria

My leukemia has progressed to a more severe stage.

I have a specific blood disorder with certain complications or treatment responses.

My leukemia has not responded well to initial treatments or has come back after a transplant.

Exclusion Criteria

I have had a fungal infection recently or it's still active.

I have hepatitis B or C with a detectable viral load.

Pregnancy, breastfeeding or unwillingness to use appropriate contraception.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Regimen

Patients receive a myeloablative conditioning regimen prior to transplantation

1 week

Transplantation

CD34+ product is expanded with UM171 and infused on Day 0; CD34- product is infused on Day +1

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment, including neutrophil and platelet engraftment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• ECT-001-CB (UM171-Expanded Cord Blood Transplant)

Trial Overview The study tests ECT-001-CB (UM171-Expanded Cord Blood Transplant) in patients with high-risk blood cancers. It aims to improve outcomes of cord blood transplants by using a molecule that helps stem cells renew themselves. This could lead to faster recovery post-transplant and better survival rates.

How Is the Trial Designed?

Group I: ECT-001-Expanded CB Experimental Treatment 1 Intervention

Patients will receive a myeloablative conditioning regimen. The cord to be expanded will undergo CD34+ selection. The CD34- product is cryopreserved and will be thawed and infused on Day +1 post-transplant. The CD34+ product will be placed in a closed culture with UM171 for a 7-day expansion and is infused on Day 0. Patients will receive standard supportive care and GVHD prophylaxis (such as MMF and tacrolimus).

ECT-001-CB (UM171-Expanded Cord Blood Transplant) is already approved in European Union, United States for the following indications:

Approved in European Union as ECT-001-CB for:

• Haematological malignancies

Approved in United States as ECT-001-CB for:

• High-risk myeloid malignancies

Who Is Running the Clinical Trial?

ExCellThera inc.

Lead Sponsor

Trials

5

Recruited

90+

Fred Hutchinson Cancer Center

Collaborator

Trials

583

Recruited

1,341,000+

Published Research Related to This Trial

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]

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]

Cord blood transplantation (CBT) is recognized as a valuable alternative source for stem cell transplants, and future efforts should focus on enhancing its applications and methods, including personalized protocols and advanced therapies to improve patient outcomes.

The concept of 'CB banking 2.0' is proposed, which aims to expand the role of cord blood banks beyond transplantation to support cell therapy and regenerative medicine, necessitating international collaboration among specialists and clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The wider perspective: cord blood banks and their future prospects. Querol, S., Rubinstein, P., Madrigal, A.[2021]

Umbilical cord blood (UCB) has become a viable alternative for stem cell transplantation, especially for patients without HLA-matched donors, with over 3500 transplants performed, primarily in children but also in adults.

UCB's unique properties allow for the use of HLA-mismatched grafts without significantly increasing the risk of severe graft versus host disease, and its rich NK cell content can enhance the graft versus leukemia effect, although challenges like low stem cell yields remain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation--how, when and for whom? Cohen, Y., Nagler, A.[2022]

Cord blood transplantation (CBT) is increasingly popular in Japan, with over 1,200 procedures performed annually, and it accounts for nearly one-third of all CBTs worldwide, benefiting from factors like smaller body size and lower costs.

Recent findings indicate that while CBT has unique challenges, such as specific infectious complications and mechanisms of engraftment failure, it shows comparable survival rates to HLA-matched bone marrow or peripheral blood transplants, suggesting its efficacy as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood transplantation in Japan. Uchida, N.[2017]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10539875/

Improved outcomes of UM171–expanded cord blood ... A UM171 CB transplant leads to lower nonrelapse mortality compared with a standard CB and MUD transplant. A UM171 cord transplant has a higher ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04103879

NCT04103879 | US Study of UM171-Expanded CB in ... Cord blood (CB) transplants are an option for patients lacking an HLA identical donor but are hampered by low cell dose, prolonged aplasia and high ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4916/533480/Long-Term-Follow-up-of-UM171-Expanded-Cord-Blood

Long Term Follow up of UM171 Expanded Cord Blood ... Examined clinical outcomes included 2ary graft failure, relapse, ≥ grade 3 AEs between years 2-5 post transplant, CD4 counts at 2 years ...

4. 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 ...

5. cordexbio.com cordexbio.com/2023/08/um171-expanded-cell-therapy-improves-outcomes-compared-with-other-graft-sources-real-world-evidence/

UM171-Expanded Cell Therapy improves outcomes ... UM171-expanded Cell Therapy demonstrated improved outcomes compared to matched unrelated donor (MUD) peripheral blood stem cell (PBSC) transplants and cord ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT03441958

NCT03441958 | ECT-001 (UM171) Expanded Cord Blood ... 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 ...

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

Paper: UM171 Expanded Cord Blood Transplantation ... The aim of the current analysis was to compare outcomes after a UM171 CBT to real-world cohorts of 6 other stem cell sources identified in the ...