Expanded Cord Blood Transplant for High-Risk Leukemia

Overseen By Andromachi Scaradavou, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: ExCellThera inc.

Disqualifiers: Uncontrolled infection, HIV, Hepatitis B/C, others

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

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

Compensation: Varies

Number of Visits: Unknown

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of expanding cord blood, a type of stem cell source, to enhance its effectiveness in treating certain blood cancers. The goal is to assist children and young adults with difficult-to-treat leukemias who lack a perfect donor match for a traditional transplant. The treatment, ECT-001-CB (UM171-Expanded Cord Blood Transplant), aims to enhance the body's recovery and reduce complications post-transplant. Individuals with high-risk blood cancers, such as acute myeloid leukemia or myelodysplastic syndrome, who have struggled with other treatments, might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research focuses on understanding the treatment's function in people and assessing its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the UM171-expanded cord blood transplant (ECT-001-CB) is promising in terms of safety. In earlier studies, this treatment helped 98% of patients recover their neutrophils (a type of white blood cell important for fighting infections) within 17 days, indicating a positive sign of quick recovery.

One year after the transplant, the risk of serious treatment-related problems remained low. Only 10% of patients experienced significant transplant-related deaths. Severe acute GVHD (graft-versus-host disease, where the donated cells attack the body) occurred in 13% of patients, while chronic GVHD was even lower at 2%. These numbers are encouraging because GVHD is a common concern with transplants.

Additionally, the risk of severe infections decreased, and most patients (77%) could stop using drugs that suppress the immune system within a year. This outcome is favorable because fewer infections mean better health and fewer hospital visits.

Overall, these findings suggest that the UM171-expanded cord blood transplant is well-tolerated and offers a lower risk of common transplant issues, making it a potentially safer option for those considering joining this clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the traditional bone marrow or cord blood transplants typically used for high-risk leukemia, which often face challenges like limited cell numbers, the ECT-001-CB treatment expands cord blood cells using a compound called UM171. This expansion boosts the number of stem cells available for transplant, potentially improving the success rate and speed of engraftment. Researchers are excited because this approach could lead to faster recovery times and reduce complications like graft-versus-host disease, making it a promising option for patients who need more robust treatment solutions.

What evidence suggests that the ECT-001-CB protocol is effective for high-risk leukemia?

Research has shown that UM171-expanded cord blood transplants, which participants in this trial will receive, hold promise for patients with high-risk leukemia. In earlier studies, 98% of patients quickly and strongly recovered their neutrophils (a type of white blood cell) by day 17 after the transplant. The risk of transplant-related death was only 10% one year after the procedure, and the chance of severe graft-versus-host disease (where the transplanted cells attack the body) was low. Patients also experienced fewer serious infections, and most could stop taking immune-suppressing drugs within a year. The time during which the disease did not worsen was 72% at 12 months and 69% at 24 months, demonstrating strong long-term effectiveness. These findings suggest that UM171-expanded cord blood could be a valuable option for patients without fully matched donors. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for pediatric and young adult patients with high-risk myeloid malignancies, such as Acute Myeloid Leukemia or Chronic Myelogenous Leukemia in blast crisis. Participants need a suitable cord blood match, good organ function, and no uncontrolled infections or other recent treatments that could affect the study.

Inclusion Criteria

Acute Myeloid Leukemia with chemo-refractory relapse (MRD+), primary induction failure, relapse after previous allogeneic or autologous transplant (>4 months), secondary or therapy-related MDS/AML, poor response to induction, Myelodysplastic syndrome with relapse after allogeneic or autologous transplant (>4 months), ≥10% blasts within 30 days of start of conditioning regimen, poor and very poor cytogenetics abnormalities, Chronic myelogenous leukemia patients who progressed to blast crisis, Mixed Phenotype Acute Leukemia with MRD+ or relapse after previous transplant (>4 months), JMML with availability of 2 ≥ 4/8 HLA matched CBU, Lansky / Karnofsky >60%, specific blood count requirements, specific liver function tests, specific kidney function tests, specific cardiac function test, signed written informed consent, and female patients of childbearing potential must have a negative serum pregnancy test within 7 days of enrollment and must be willing to use an effective contraceptive method while enrolled in the study.

Exclusion Criteria

Previous allogeneic transplantation within 4 months, uncontrolled infection, presence of other malignancy with expected survival less than 75% at 5 years, seropositive for HIV, Hep B and C infection with measurable viral load, liver cirrhosis, active CNS disease, Chloroma > 2cm, >30% blasts in marrow, pregnancy, breastfeeding, unwillingness to use appropriate contraception, participation in a trial with an investigational agent within 30 days prior to entry in the study, and any abnormal condition or lab result that is considered capable of altering patient's condition or study outcome.

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 (Preferred: Clo/Flu/Bu90, Alternative: MIDI) before transplantation

1 week

Transplantation

The CD34+ product is expanded with UM171 and infused on Day 0, while the CD34- product is infused on Day +1 post-transplant

1 week

Engraftment and Early Recovery

Monitoring for hematologic engraftment and early recovery, including neutrophil and platelet engraftment

100 days

Follow-up

Participants are monitored for safety, effectiveness, and incidence of GVHD and infections post-transplant

2 years

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The trial tests ECT-001-CB (UM171-Expanded Cord Blood Transplant) to improve outcomes of cord blood transplants by increasing cell dose and reducing complications like graft-versus-host disease. The first stage includes 12 patients; if successful, it will expand to more centers with additional participants.

How Is the Trial Designed?

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

Patients will receive a myeloablative conditioning regimen (Preferred: Clo/Flu/Bu90, Alternative: MIDI) 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+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

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]

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 of 90 adults undergoing double-unit cord blood transplantation (CBT) with an intermediate intensity conditioning regimen, the procedure achieved a high sustained engraftment rate of 99% and a 3-year overall survival rate of 82%.

The use of unmanipulated grafts with significant HLA mismatches allowed for broader application of CBT, demonstrating low relapse rates and effective graft-versus-leukemia effects, even in patients with minimal residual disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High progression-free survival after intermediate intensity double unit cord blood transplantation in adults. Barker, JN., Devlin, SM., Naputo, KA., et al.[2023]

A new device allows for the selective thawing of just 1 mL of umbilical cord blood (UCB), enabling the remaining UCB to be preserved for future use, which could enhance treatment options for leukemia.

This method successfully expanded large numbers of natural killer (NK) cells from the thawed UCB, which showed strong cytotoxicity against leukemia cells, suggesting potential for preventing relapse and reducing complications like graft-versus-host disease after transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel method to expand large numbers of CD56(+) natural killer cells from a minute fraction of selectively accessed cryopreserved cord blood for immunotherapy after transplantation. Vasu, S., Berg, M., Davidson-Moncada, J., et al.[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]

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]

In a phase 2 study involving 62 adult patients with leukemia and myelodysplastic syndrome, single-unit cord blood transplantation (CBT) demonstrated an 85% survival rate at day 180, indicating its efficacy as a treatment option.

The study also reported a high neutrophil engraftment rate of 92%, with manageable incidences of graft-versus-host disease, suggesting that CBT can be a safe alternative when a well-HLA-matched unrelated donor is not available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Phase 2 Study of Umbilical Cord Blood Transplantation in Adult Acute Leukemia and Myelodysplastic Syndrome. Terakura, S., Nishida, T., Sawa, M., et al.[2021]

Ex vivo expansion of a single cord blood unit (CBU) using mesenchymal stromal cells (MSCs) significantly enhances the hematopoiesis of an unexpanded CBU in a double cord blood transplantation (DCBT) setting, leading to improved survival rates in mice.

The expanded CBU resulted in a lower incidence of graft versus host disease (GVHD), likely due to an increase in regulatory T cells, suggesting a safer approach to DCBT with potential benefits for patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal cell supported umbilical cord blood ex vivo expansion enhances regulatory T cells and reduces graft versus host disease. Fan, X., Gay, FP., Ong, SY., et al.[2018]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03913026?term=AREA%5BBasicSearch%5D(AREA%5BNCTIdSearch%5D(nct03913026))&rank=1

UM171 Expanded Cord Blood In Patients With High-Risk ... Patients with high and very high-risk acute leukemia/myelodysplasia will receive a single 5-7/8 HLA matched ECT-001 (UM171) expanded cord blood after an ...

2. 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 ... Between 2019 and 2022, 30 patients with high and very high-risk myelodysplasia/acute leukemia underwent a single UM171 CBT on a phase II trial.

3. 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 ...

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. clinicaltrials.gov clinicaltrials.gov/study/NCT03441958?spons=COVERAGE%5BFullMatch%5DEXPANSION%5BNone%5D(%22ExCellThera%20inc.%22)&viewType=Table&rank=4

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

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

A Pilot Study of UM171-Expanded Cord Blood Grafts for ... UM171-expanded CB transplant in HR/ultra-HR myeloma patients is feasible and allows the use of single CB units with a low risk of cGVHD.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04103879

NCT04103879 | US Study of UM171-Expanded CB in ... In a previous trial (NCT02668315), the CB expansion protocol using the ECT-001-CB technology (UM171 molecule) has proven to be technically feasible and safe.