Dilanubicel + Cord Blood Transplant for Leukemia and Myelodysplastic Syndromes

Overseen By Filippo Milano

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Research Center

Disqualifiers: Uncontrolled infection, HIV, Pregnancy, 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: 181

35 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well donor umbilical cord blood transplant with ex-vivo expanded cord blood progenitor cells (dilanubicel) works in treating patients with blood cancer. Before the transplant, patients will receive chemotherapy (fludarabine, cyclophosphamide and in some cases thiotepa) and radiation therapy. Giving chemotherapy and total-body irradiation before a donor umbilical cord blood transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may also replace the patient's immune cells and help destroy any remaining cancer cells.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves chemotherapy and radiation, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators or your doctor for specific guidance.

What data supports the effectiveness of the treatment Dilanubicel + Cord Blood Transplant for Leukemia and Myelodysplastic Syndromes?

Umbilical cord blood transplantation (UCBT) is increasingly used to treat acute leukemias and has shown results comparable to other stem cell sources, with advantages like lower incidence of complications and easier availability. Recent strategies to increase the number of cord blood progenitors could further improve outcomes for patients with leukemia receiving UCBT. ^{1 2 3 4 5}

Is the Dilanubicel + Cord Blood Transplant treatment generally safe for humans?

Umbilical cord blood transplantation is generally considered safe, with a lower risk of severe graft-versus-host disease (a condition where the donated cells attack the recipient's body) compared to other donor sources. However, patients may experience mild to severe infusion reactions and are at high risk of infections due to delayed immune recovery. ^{1 6 7 8 9}

What makes the Dilanubicel + Cord Blood Transplant treatment unique for leukemia and myelodysplastic syndromes?

This treatment is unique because it combines umbilical cord blood transplantation, which uses stem cells from cord blood to help regenerate healthy blood cells, with Dilanubicel, potentially enhancing the immune response to prevent or treat leukemia relapse. It offers an alternative for patients who do not have suitable bone marrow donors. ^{1 2 4 7 10}

Research Team

Filippo Milano

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

This trial is for patients aged 18-65 with acute leukemia, chronic myeloid leukemia, or myelodysplastic syndromes who are eligible for a cord blood transplant. Participants must have good heart function and kidney health, no uncontrolled infections or recent severe fungal infections, not be HIV positive or pregnant, and haven't had a prior allogeneic transplant.

Inclusion Criteria

My kidney, liver, lung, and heart functions meet the required health standards.

I can understand and am willing to sign the consent form.

My donated cord blood meets the minimum matching and cell dose requirements.

Exclusion Criteria

I weigh less than 30 kg.

Pregnant or breastfeeding

I do not have an uncontrolled infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Chemotherapy and Radiation

Patients receive chemotherapy (fludarabine, cyclophosphamide, and thiotepa) and total body irradiation before the transplant

8 days

Transplantation

Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Visits at 180 days, 1 year, and 2 years

Treatment Details

Interventions

• Cyclophosphamide
• Ex-Vivo Expanded Cord Blood Progenitor Cell Infusion
• Fludarabine
• Thiotepa
• Total-Body Irradiation
• Umbilical Cord Blood Transplantation

Trial Overview The study tests if a donor umbilical cord blood transplant combined with dilanubicel (expanded cord blood cells) after chemotherapy (fludarabine, cyclophosphamide) and radiation therapy can effectively treat blood cancers by replacing bone marrow stem cells and boosting the immune system to fight cancer.

Participant Groups

Group I: Treatment (chemotherapy, TBI, NLA101) Experimental Treatment 13 Interventions

Patients receive either regimen A or regimen B. REGIMEN A: Patients (10 through 45 years old) receive fludarabine IV over 30 minutes on days -8 to -6 and cyclophosphamide IV on days -7 and -6. Patients undergo TBI BID on days -4 to -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0. REGIMEN B: Patients (10 through 65 years old) receive fludarabine IV over 30-60 minutes on days -6 to -3 and IV over 30 minutes on day -2, cyclophosphamide IV on day -6, and thiotepa IV over 2-4 hours on days -5 and -4. Patients undergo TBI QD on days -2 and -1. Patients receive unmanipulated cord blood unit IV followed by dilanubicel IV within the next 24 hours on day 0. All patients undergo bone marrow aspirate and biopsy as clinically indicated during screening and on study. Patients undergo MUGA or ECHO, and CT during screening. Patients also undergo blood sample collection on study.

Umbilical Cord Blood Transplantation is already approved in United States, European Union for the following indications:

Approved in United States as Umbilical Cord Blood Transplantation for:

• Acute Leukemia
• Chronic Myeloid Leukemia
• Myelodysplastic Syndromes

Approved in European Union as Umbilical Cord Blood Transplantation for:

• Acute Leukemia
• Chronic Myeloid Leukemia
• Myelodysplastic Syndromes

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Research Center

Lead Sponsor

Trials

444

Recruited

148,000+

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Nohla Therapeutics, Inc.

Industry Sponsor

Trials

6

Recruited

400+

Findings from Research

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 transplantation for patients with acute myeloid leukemia, myelodysplastic syndrome, and chronic myelogenous leukemia shows similar relapse rates and survival outcomes compared to other sources of hematopoietic stem cells.

The disease status at the time of transplantation is crucial for long-term outcomes, and newer strategies like double umbilical cord blood transplants and nonmyeloblative conditioning regimens are showing promising results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation for myeloid malignancies. Brunstein, CG., Baker, KS., Wagner, JE.[2007]

In a study involving 4 patients, umbilical cord blood-derived T cells (UCB DLI) were administered as a potential alternative to conventional donor lymphocyte infusion, showing no adverse reactions during transfusion and minimal signs of graft-versus-host disease (GVHD) in most cases.

One patient with minimal residual disease showed a significant reduction in detectable malignant cells after receiving UCB DLI, suggesting potential therapeutic benefits, although a direct causal relationship could not be established.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanded umbilical cord blood T cells used as donor lymphocyte infusions after umbilical cord blood transplantation. Berglund, S., Gertow, J., Uhlin, M., et al.[2017]

Umbilical cord blood (UCB) is increasingly being used for stem cell transplantation, particularly for treating hematological malignancies in both children and adults, thanks to advancements like double UCB and reduced-intensity transplantation methods.

Ongoing clinical trials and registry analyses are focused on improving the accessibility and effectiveness of UCB transplantation, addressing current challenges in the field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future of cord blood for oncology uses. Brunstein, CG., Weisdorf, DJ.[2009]

Umbilical cord blood transplantation (UCBT) is a safe and effective treatment for children with hematological malignancies, offering a comparable probability of cure to bone marrow transplantation (BMT) while having a lower risk of graft-versus-host disease.

Recent strategies to increase the number of nucleated cord blood cells infused may further improve outcomes for children undergoing UCBT, particularly in reducing transplantation-related mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood transplantation in children with haematological malignancies. Bertaina, A., Bernardo, ME., Caniglia, M., et al.[2010]

Umbilical cord blood transplantation is a safer and simpler procedure compared to bone marrow transplantation, posing no health risks to the mother or fetus during collection.

Over the past 10 years, results from European Transplantation Centers have shown that umbilical cord blood transplantation is a promising alternative treatment for patients with oncological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Transplantation of hematopoietic stem cells from umbilical cord blood]. Gŭrcheva, L., Nikolov, A., Gŭrchev, E., et al.[2006]

In a study involving 13 patients with leukemia, double-unit umbilical cord blood transplantation (UCBT) showed a high engraftment rate, with 92.3% of patients achieving neutrophil and platelet engraftment within a median of 21 and 34 days, respectively.

The procedure demonstrated a manageable safety profile, with only one case of grade II acute graft-versus-host disease and limited chronic GVHD in survivors, suggesting that double-unit UCBT can be a feasible option for adults and adolescents with leukemia despite HLA mismatches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in adults with leukemia treated with transplantation of two unrelated umbilical cord blood units. Yin, Y., Ren, HY., Cen, XA., et al.[2011]

Umbilical cord blood transplants are a valuable alternative for treating blood cancers, offering rapid availability and less strict matching requirements, which can reduce the risk of relapse and graft-versus-host disease.

Double-unit umbilical cord blood transplants may improve neutrophil recovery rates and address the issue of limited cell doses, especially in adult patients, while also serving as a platform for testing new expansion and homing techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should double cord blood transplants be the preferred choice when a sibling donor is unavailable? Wagner, JE.[2021]

Umbilical cord blood (UCB) transplantation has become more common, but patients may face unique challenges such as delayed immune recovery and prolonged transfusion dependence due to slower engraftment of UCB cells.

Despite these challenges, UCB transplant patients experience a lower rate of graft versus host disease compared to those receiving stem cells from adult donors, which may be a significant advantage in their treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation: review of factors affecting the hospitalized patient. Delaney, M., Ballen, KK.[2014]

In a study of 13 adult patients with advanced myelodysplastic syndrome (MDS), unrelated cord blood transplantation (CBT) showed promising results, with a 76.2% probability of disease-free survival at 2 years.

Most patients experienced myeloid reconstitution, with significant recovery of neutrophil and platelet counts, although acute and chronic graft versus host disease (GVHD) were common complications, affecting 9 and 8 patients respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unrelated cord blood transplantation for adult patients with advanced myelodysplastic syndrome. Ooi, J., Iseki, T., Takahashi, S., et al.[2021]

References

1. England 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. [2021]

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

Umbilical cord blood transplantation for myeloid malignancies. [2007]

3. England pubmed.ncbi.nlm.nih.gov

Expanded umbilical cord blood T cells used as donor lymphocyte infusions after umbilical cord blood transplantation. [2017]

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

Future of cord blood for oncology uses. [2009]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Cord blood transplantation in children with haematological malignancies. [2010]

6. Bulgaria pubmed.ncbi.nlm.nih.gov

[Transplantation of hematopoietic stem cells from umbilical cord blood]. [2006]

7. China pubmed.ncbi.nlm.nih.gov

Long-term outcomes in adults with leukemia treated with transplantation of two unrelated umbilical cord blood units. [2011]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Should double cord blood transplants be the preferred choice when a sibling donor is unavailable? [2021]

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

Umbilical cord blood transplantation: review of factors affecting the hospitalized patient. [2014]

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

Unrelated cord blood transplantation for adult patients with advanced myelodysplastic syndrome. [2021]