Umbilical Cord Blood Transplant for Blood Cancers

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Specified in treatment protocol

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

250 Participants Needed

Trial Summary

What is the purpose of this trial?

For the next 5-10 years or possibly longer, a high proportion of the Cord Blood Banks (CBB) inventory worldwide will be composed of unlicensed umbilical cord blood (UCB) units. While Food and Drug Administration (FDA)-licensed units will be prioritized, it will always be possible that an unlicensed unit will have known attributes, making it a better source of cells for the given indication. Because of the wide variety of current and potential indications as a source of cells for hematopoietic reconstitution or other form of cellular therapy, it is critical that the investigators have access to unlicensed UCB units.

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 for umbilical cord blood transplantation in blood cancers?

Umbilical cord blood (UCB) has been shown to be an effective source of stem cells for transplantation in patients with blood cancers, providing similar survival outcomes to other stem cell sources, especially in children. UCB is advantageous due to its availability and successful outcomes even with some donor-recipient mismatches, although improvements are needed for better recovery and reduced early transplant-related deaths. ^{1 2 3 4 5}

Is umbilical cord blood transplantation generally safe for humans?

Umbilical cord blood transplantation is considered safe and has a low incidence of chronic graft-versus-host disease (a condition where the donor's cells attack the recipient's body). It has been used successfully in adults with leukemia, although the low cell dose in a single unit can be a limitation. ^{2 3 4 6 7}

How is umbilical cord blood transplantation different from other treatments for blood cancers?

Umbilical cord blood transplantation is unique because it uses stem cells from umbilical cord blood, which can be a valuable option for patients without a matched donor. This treatment can involve using two units of cord blood to overcome the limitation of low cell numbers, potentially improving outcomes for patients with blood cancers. ^{8 9 10 11 12}

Research Team

John Wagner, MD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Eligibility Criteria

This trial is for patients needing a stem cell transplant to treat blood or lymphatic diseases and who have an unlicensed umbilical cord blood (UCB) unit that matches their needs. The UCB must be free of pathogens, with no equivalent licensed option available. Participants must consent to use the UCB as part of another approved treatment plan.

Inclusion Criteria

I (or my guardian) have agreed to use an experimental treatment as part of a clinical trial.

I am eligible for a treatment that requires stem cells from umbilical cord blood after a bone marrow preparation procedure.

I have a cord blood unit that matches and is free of blood-borne diseases, not from a licensed bank.

Exclusion Criteria

Exclusion criteria are specified in the treatment protocol according to indication.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-infusion Treatment

Participants receive intravenous hydration, acetaminophen, and diphenhydramine hydrochloride prior to UCB infusion

Approximately 30 minutes

Infusion

Infusion of minimally manipulated unlicensed UCB units with vital signs monitoring and management of infusion reactions

Within 24 hours

Post-transplant Care and Follow-up

Participants are monitored for safety and effectiveness, including incidence of serious infusion reactions and blood borne pathogen transmission

Up to 180 days

Treatment Details

Interventions

• Infusion of Cell Populations From Unlicensed Umbilical Cord Blood Units

Trial Overview The study tests the infusion of unlicensed UCB units in treating various conditions requiring hematopoietic stem cells from cord blood after intensive chemotherapy or radiation therapy, known as myeloablative or non-myeloablative conditioning.

Participant Groups

Group I: Unlicensed Umbilical Cord Blood Infusion Experimental Treatment 1 Intervention

All patients will be registered in OnCore under this protocol as well as the specific treatment protocol. * Pre-infusion treatment using intravenous hydration, acetaminophen and diphenhydramine hydrochloride * Unlicensed Umbilical Cord Blood Infusion according to institutional guidelines. * Infusion of minimally manipulated unlicensed UCB units: * vital signs Monitoring during and after UCB infusion: * Management of infusion reactions * Post-transplant care and follow-up: will be done according to the disease specific treatment protocol and institutional guidelines.

Infusion of Cell Populations From Unlicensed Umbilical Cord Blood Units is already approved in United States, European Union for the following indications:

Approved in United States as Umbilical Cord Blood Transplantation for:

• Hematopoietic reconstitution for inherited, acquired, or myeloablative treatment-related disorders
• Leukemia
• Hemoglobinopathies
• Fanconi’s anemia
• Immune or metabolic disorders

Approved in European Union as Umbilical Cord Blood Transplantation for:

• Hematopoietic reconstitution for malignant and non-malignant disorders
• Acute leukemia
• Hemoglobinopathies
• Fanconi’s anemia
• Immune or metabolic disorders

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Findings from Research

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]

The study found that the technique used for collecting umbilical cord blood (UCB) significantly affects the total nucleated cell (TNC) count and overall quality of the UCB units, which are crucial for successful stem cell transplants.

Factors such as maternal age, gestational age, type of pregnancy, and newborn weight were correlated with UCB quality, leading to a re-evaluation of collection protocols to enhance transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cross-sectional study of umbilical cord blood donor profiles and their influence on umbilical cord blood collection in a Brazilian hospital. Valéria Santos, S., Marti, L., Ribeiro, AA., et al.[2018]

A survey in the St. Louis area revealed that many women are hesitant to donate umbilical cord blood (UCB) due to nervousness and lack of information, highlighting the need for better education on the benefits and process of donation.

Despite these concerns, 62% of surveyed women did donate UCB, indicating that with improved communication and dedicated personnel at hospitals, more donations could be encouraged, particularly from minority populations who often face challenges in finding compatible donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Awareness of cord blood collection and the impact on banking. Bhandari, R., Lindley, A., Bhatla, D., et al.[2017]

Transplanting two units of umbilical cord blood (UCB) significantly improves the engraftment of human hematopoietic cells in mice compared to using a single unit, suggesting a potential strategy to enhance recovery in patients with low cell doses.

The study indicates that the improved engraftment from double UCB transplantation may be due to either a higher total cell dose or a beneficial interaction between the two different UCB units, as some recipients showed similar engraftment levels to those receiving a single unit with an equal cell count.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced engraftment of umbilical cord blood-derived stem cells in NOD/SCID mice by cotransplantation of a second unrelated cord blood unit. Nauta, AJ., Kruisselbrink, AB., Lurvink, E., et al.[2006]

Umbilical cord blood (UCB) has become a valuable alternative for hematopoietic cell transplantation, especially for patients without a matched donor, showing similar leukemia-free survival rates in children when compared to HLA-matched unrelated donor bone marrow.

While UCB transplants have some limitations, such as slower hematopoietic recovery and higher early transplant-related deaths, ongoing research aims to address these issues, highlighting the importance of HLA matching and cell dose in improving outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transplant outcomes in acute leukemia. I. Eapen, M., Wagner, JE.[2021]

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]

A total of 8623 umbilical cord blood (UCB) units were collected in a provincial bank in Guangzhou, China, with 4147 units (48.1%) stored for potential transplantation, demonstrating effective donor screening and processing protocols.

The study reported high cell viability (97.8%) and successful engraftment times for transplanted patients, with children showing faster neutrophil engraftment (17 days) compared to adults (20 days), indicating the efficacy of UCB as a source of hematopoietic stem cells for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Banking and transplantation of umbilical cord blood in Guangzhou, China. Wu, JY., Liao, C., Xu, ZP., et al.[2008]

In a study involving 61 children and adolescents undergoing double umbilical cord blood transplantation (UCBT), donor-type engraftment was achieved in 82% of patients, indicating a promising potential for this treatment in overcoming low cell number limitations.

Event-free survival rates were 59% for leukemia and 53% for other hematologic diseases, with significantly better outcomes for acute leukemia patients who received transplants in earlier disease stages, highlighting the importance of timing in transplantation success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double umbilical cord blood transplantation for children and adolescents. Kang, HJ., Yoo, KH., Lee, JW., et al.[2021]

Intravesical Bacillus Calmette-Guérin (BCG) treatment, typically contraindicated for immunocompromised patients, was successfully administered to a bladder cancer patient who had undergone umbilical cord blood stem cell transplantation (UCBSCT).

The case suggests that BCG can be safely and effectively used in select patients at least 2 years post-UCBSCT, indicating potential for broader application in similar immunocompromised individuals with reconstituted immune systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safe and effective administration of BCG for bladder carcinoma in situ after umbilical cord blood stem cell transplantation. Magaribuchi, T., Akamatsu, S., Kobayashi, T., et al.[2018]

In a meta-analysis of 3434 participants across seven studies, haplo-identical transplants using post-transplant cyclophosphamide (PTCy-haplo) showed a significantly lower risk of acute graft-versus-host disease (aGVHD) and relapse compared to umbilical cord transplants (UC).

The PTCy-haplo group also demonstrated improved overall survival rates, although it was associated with a higher risk of chronic graft-versus-host disease (cGVHD) compared to UC transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post transplant cyclophosphamide based haplo-identical transplant versus umbilical cord blood transplant; a meta-analysis. Poonsombudlert, K., Kewcharoen, J., Prueksapraopong, C., et al.[2020]

Circulating tumor cells (CTC) were found in 23% of patients with nonmetastatic urothelial carcinoma of the bladder, and their presence was linked to significantly higher risks of disease recurrence and mortality, making CTC a strong predictor of patient outcomes.

The study suggests that molecular characterization of CTC could be used as a liquid biopsy to guide targeted therapy, indicating a potential for personalized treatment strategies in future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic role and HER2 expression of circulating tumor cells in peripheral blood of patients prior to radical cystectomy: a prospective study. Rink, M., Chun, FK., Dahlem, R., et al.[2022]

Intracavitary chemotherapy for upper tract urothelial carcinoma (UTUC) shows promising efficacy, with an overall survival rate of 87.2% and a cancer-specific survival rate of 94.1% over a median follow-up of 30 months, based on a meta-analysis of 34 studies involving 788 patients.

The recurrence rate of UTUC was found to be 27.5%, with lower rates observed for the new drug UGN101 (12.9%) compared to traditional treatments like Mitomycin C (41.3%), suggesting that kidney-sparing therapies are becoming more effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intracavitary Chemotherapy after kidney-Sparing Therapy for Upper Tract Urothelial Carcinoma: A Meta-Analysis. Zhou, H., Pan, Y., Xu, M., et al.[2023]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

A cross-sectional study of umbilical cord blood donor profiles and their influence on umbilical cord blood collection in a Brazilian hospital. [2018]

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

Awareness of cord blood collection and the impact on banking. [2017]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Enhanced engraftment of umbilical cord blood-derived stem cells in NOD/SCID mice by cotransplantation of a second unrelated cord blood unit. [2006]

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

Transplant outcomes in acute leukemia. I. [2021]

6. China pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

Banking and transplantation of umbilical cord blood in Guangzhou, China. [2008]

8. Germany pubmed.ncbi.nlm.nih.gov

Double umbilical cord blood transplantation for children and adolescents. [2021]

9. Denmark pubmed.ncbi.nlm.nih.gov

Safe and effective administration of BCG for bladder carcinoma in situ after umbilical cord blood stem cell transplantation. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Post transplant cyclophosphamide based haplo-identical transplant versus umbilical cord blood transplant; a meta-analysis. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Prognostic role and HER2 expression of circulating tumor cells in peripheral blood of patients prior to radical cystectomy: a prospective study. [2022]

12. Iran pubmed.ncbi.nlm.nih.gov

Intracavitary Chemotherapy after kidney-Sparing Therapy for Upper Tract Urothelial Carcinoma: A Meta-Analysis. [2023]