Cord Blood Transplant for Blood Disorders

Recruiting at 1 trial location

Overseen By Richard W Childs, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Disqualifiers: Licensed CB products, Unlicensed CB from NMDP

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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

500 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: - Cord blood is blood that is taken from the umbilical cord and placenta of healthy newborns after childbirth. The cord blood collected from a baby is called a cord blood unit. Cord blood units are stored frozen in public cord blood banks. About 10,000 cord blood transplants have been performed in children and adults for blood cancers and other diseases in the world. These transplants have helped save lives and improve treatments. However, not all available units of cord blood have been collected, stored, and licensed according to specific government requirements. These unlicensed units can still be used in transplant, but they can only be given as part of specific research studies. This study will evaluate the safety of giving these unlicensed units by recording any problems that may occur during and after giving the cord blood. Objectives: - To test the safety and effectiveness of unlicensed cord blood units in people who need stem cell transplants. Eligibility: - Individuals who are scheduled to have a stem cell transplant. Design: Participants will be screened with a medical history and physical exam. Participants will receive the cord blood unit as part of their stem cell transplant procedure. The transplant will be performed according to the current standard of care for the procedure. After the transplant, participants will be monitored for up to 1 year. Any problems or side effects from the transplant will be treated as necessary. All outcomes will be reported to the National Cord Blood Program and to the Center for International Blood and Marrow Transplant.

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 Cord Blood Transplant for Blood Disorders?

Research shows that using two umbilical cord blood units for transplantation in children and adolescents with blood disorders like leukemia has promising results, with 82% of patients achieving successful donor cell growth and a survival rate of 59% for leukemia patients. ^{1 2 3 4 5}

Is cord blood transplantation generally safe for humans?

Cord blood transplantation is generally considered safe, with studies showing it poses no health risks to the mother or fetus during collection. However, there are some risks of adverse events, and the safety of the procedure can vary depending on factors like cell dose and donor matching. ^{6 7 8 9 10}

How is cord blood transplant different from other treatments for blood disorders?

Cord blood transplant is unique because it uses stem cells from umbilical cord blood, which are quickly available and can be used when a matching donor is not found. This treatment is especially beneficial for patients who need a transplant urgently, and it has shown success in treating various blood disorders, although it may take longer to engraft compared to other sources. ^{11 12 13 14 15}

Research Team

Richard W Childs, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

This trial is for individuals of any age and gender who need a stem cell transplant due to conditions like leukemia, lymphoma, or anemia. They must be part of another clinical trial for the transplant and give informed consent. Those already receiving unlicensed cord blood from other banks or licensed products only cannot participate.

Inclusion Criteria

I am eligible for a stem cell transplant trial using cord blood.

Signed informed consent (and assent when applicable).

Exclusion Criteria

I am currently using approved cannabinoid-based products.

You are currently receiving unapproved cord blood products from sources other than the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive the cord blood unit as part of their stem cell transplant procedure, performed according to the current standard of care

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the transplant, with all outcomes reported to the National Cord Blood Program and the Center for International Blood and Marrow Transplant

1 year

Regular visits as per protocol

Treatment Details

Interventions

• Cord Blood Units

Trial Overview The study tests the safety and effectiveness of unlicensed cord blood units used in stem cell transplants. Participants will receive these units during their standard transplant procedure and will be monitored for up to one year for any issues.

Participant Groups

Group I: 1 Experimental Treatment 1 Intervention

at least one

Cord Blood Units is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Umbilical Cord Blood Units for:

• Acute Leukemia
• Hemoglobinopathies
• Fanconi’s Anemia
• Immune or Metabolic Disorders
• Neuroblastoma
• Thalassemia
• Severe Combined Immunodeficiency (SCID)
• Wiskott-Aldrich Syndrome
• Metabolic Diseases

Approved in United States as Cord Blood Units for:

• Blood Cancers
• Leukemia
• Lymphoma
• Bone Marrow Failure
• Aplastic Anemia
• Genetic Diseases
• Immune System Disorders

Approved in Canada as Umbilical Cord Blood Units for:

• Acute Leukemia
• Hemoglobinopathies
• Fanconi’s Anemia
• Immune or Metabolic Disorders

Approved in Japan as Cord Blood Stem Cells for:

• Leukemia
• Lymphoma
• Bone Marrow Failure
• Aplastic Anemia

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

National Cord Blood Program, New York Blood Center

Collaborator

Trials

1

Recruited

500+

Findings from Research

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]

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]

In a study of 609 patients with upper urinary tract urothelial carcinoma (UUT-UC), both open nephroureterectomy (ONU) and laparoscopic nephroureterectomy (LNU) showed similar 5-year cancer-specific survival (CSS) and recurrence-free survival (RFS) rates, indicating that LNU is a viable alternative to traditional surgery.

Postoperative complications were comparable between the two surgical approaches, suggesting that LNU does not compromise safety compared to ONU, as evidenced by a median follow-up of 27 months and no significant differences in complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of oncologic control obtained after open versus laparoscopic nephroureterectomy for upper urinary tract urothelial carcinomas (UUT-UCs): results from a large French multicenter collaborative study. Ariane, MM., Colin, P., Ouzzane, A., et al.[2022]

In a study of 147 patients with recurrent or metastatic upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy, those classified as high-risk (with 2 or more risk factors) showed improved cancer-specific survival (CSS) when treated with salvage chemotherapy (SC), with a median CSS of 9.5 months compared to 3.7 months for those not receiving SC.

Key predictive factors for high-risk patients included a pT stage of ≥pT3, recurrence within 12 months, and liver metastasis, highlighting the importance of these factors in determining treatment strategies and outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncologic Outcomes of Salvage Chemotherapy in Patients with Recurrent or Metastatic Lesions after Radical Nephroureterectomy: A Multi-Institutional Retrospective Study. Ikeda, M., Matsumoto, K., Hirayama, T., et al.[2021]

In a study of 49 patients with pyonephrosis due to upper urinary tract calculi, both transurethral ureteroscope lithotripsy and percutaneous nephrolithotomy were effective treatments, with no severe complications like septicemia reported during the initial procedures.

Follow-up over 3 months to 5.5 years showed that all patients experienced varying degrees of renal function recovery, highlighting the importance of early diagnosis and timely drainage in successfully treating this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of pyonephrosis with upper urinary tract calculi]. Tu, MQ., Shi, GW., He, JY.[2019]

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]

The FDA's guidance on donor screening to prevent Zika virus transmission has led to a significant reduction in the number of available umbilical cord blood units for transplantation, which are critical for hematopoietic stem cell therapies.

There is an urgent need for updated assessments of travel risks related to Zika, improved screening tests for Zika in cord blood, and more research on the virus's transmissibility to ensure the safety and availability of these vital medical resources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zika virus and its implications on cord blood banking and transplantation. Stone, EF., Shaz, BH.[2023]

A study analyzing 140 reported adverse events from cord blood infusions in Japan found that hypertension was the most common side effect, while serious adverse events like anaphylaxis occurred at a low frequency of 0.23%.

The research highlighted the need for standardized reporting systems for adverse events in cord blood transplantation, as existing classification criteria were unable to classify a significant number of cases, which could hinder efforts to improve safety and reduce risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events caused by cord blood infusion in Japan during a 5-year period. Hashimoto, S., Kato, K., Kai, S., et al.[2023]

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]

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]

In a study involving 224 patients aged 1 to 21 with hematologic cancer, the overall survival rates after single-unit and double-unit cord-blood transplantation were similar, with 1-year survival rates of 73% for single-unit and 65% for double-unit transplants.

However, recipients of single-unit cord-blood transplants experienced better platelet recovery and had a lower incidence of severe graft-versus-host disease (GVHD), suggesting that single-unit transplants may offer certain advantages despite similar survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

One-unit versus two-unit cord-blood transplantation for hematologic cancers. Wagner, JE., Eapen, M., Carter, S., et al.[2022]

Umbilical cord blood is a promising source of hematopoietic stem cells for treating hematologic diseases, showing high success rates in pediatric patients and improving outcomes for adults through better matching and cell doses.

Recent advancements, such as the use of double umbilical cord blood units and enhanced supportive care, have led to faster engraftment times and ongoing comparisons with other graft sources in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation: the first 25 years and beyond. Ballen, KK., Gluckman, E., Broxmeyer, HE.[2022]

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]

Umbilical cord blood (CB) is a valuable alternative source of hematopoietic stem cells for treating blood disorders, with successful transplantation linked to higher total nucleated cell and CD34+ cell counts.

Optimizing the conditions for collecting and processing cord blood can reduce graft rejection rates and improve the quality of cord blood units, ultimately enhancing the success of stem cell engraftment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of maternal and infant factors on cord blood yield. Mousavi, SH., Abroun, S., Zarrabi, M., et al.[2017]

Hematopoietic cell transplants using umbilical cord blood stem cells are effective for treating a variety of disorders, providing rapid availability which is crucial for patient prognosis.

Advancements in expanding stem cell doses and developing adoptive immunotherapy using other components of umbilical cord blood have improved engraftment and broadened treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical Cord Blood Transplants: Current Status and Evolving Therapies. Gupta, AO., Wagner, JE.[2020]

References

1. Germany pubmed.ncbi.nlm.nih.gov

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

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

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

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

Assessment of oncologic control obtained after open versus laparoscopic nephroureterectomy for upper urinary tract urothelial carcinomas (UUT-UCs): results from a large French multicenter collaborative study. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Oncologic Outcomes of Salvage Chemotherapy in Patients with Recurrent or Metastatic Lesions after Radical Nephroureterectomy: A Multi-Institutional Retrospective Study. [2021]

5. China pubmed.ncbi.nlm.nih.gov

[Treatment of pyonephrosis with upper urinary tract calculi]. [2019]

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

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

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

Zika virus and its implications on cord blood banking and transplantation. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Adverse events caused by cord blood infusion in Japan during a 5-year period. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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

10. China pubmed.ncbi.nlm.nih.gov

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

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

One-unit versus two-unit cord-blood transplantation for hematologic cancers. [2022]

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

Umbilical cord blood transplantation: the first 25 years and beyond. [2022]

13. England pubmed.ncbi.nlm.nih.gov

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

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

The effect of maternal and infant factors on cord blood yield. [2017]

15. Switzerland pubmed.ncbi.nlm.nih.gov

Umbilical Cord Blood Transplants: Current Status and Evolving Therapies. [2020]