Cord Blood Transplant for Blood Cancers

Recruiting in Palo Alto (17 mi)

+6 other locations

Overseen by Ioannis Politikos, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Memorial Sloan Kettering Cancer Center

Must not be taking: Checkpoint inhibitors

Disqualifiers: Myelofibrosis, CNS disease, HIV, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

Cord blood transplants (CBT) are a standard treatment for adults with blood cancers. MSK has developed a standard ("optimized") practice for cord blood transplant (CBT). This optimized practice includes how patients are evaluated for transplant, the conditioning treatment (standard chemotherapy and total body irradiation therapy) given to prepare the body for transplant, the amount of stem cells transplanted, and how patients are followed during and after transplant.The purpose of this study is to collect information about participant outcomes after CBT following MSK's optimized practice. The researchers will look at outcomes of the CBT treatment such as side effects, disease relapse, GVHD, and immune system recovery after CBT treatment.

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 specific guidance.

What data supports the effectiveness of this treatment for blood cancers?

Research shows that umbilical cord blood transplantation (using stem cells from umbilical cord blood) is a promising treatment for blood cancers, especially when other treatments have failed. It has advantages like better matching and lower risk of complications compared to other stem cell sources, and studies have shown it can lead to better disease control and survival rates. ^{1 2 3 4 5}

Is cord blood transplant generally safe for humans?

Cord blood transplants, like other stem cell transplants, can have serious side effects, but recent advances have made them less toxic. Studies show that using less intense conditioning treatments can reduce complications, although some risks remain, such as infections and organ-related side effects. ^{6 7 8 9 10}

How is cord blood transplant treatment different from other treatments for blood cancers?

Cord blood transplant treatment is unique because it uses stem cells from umbilical cord blood, which can be a suitable option for patients who do not have a matched donor in their family or the unrelated registry. This approach can reduce the risk of severe graft-versus-host disease and is particularly beneficial for patients from diverse ethnic backgrounds who may struggle to find a fully matched donor. ^{3 11 12 13 14}

Research Team

Ioannis Politikos, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults with various high-risk blood cancers, including different types of leukemia and lymphoma. Participants must meet specific criteria such as being in a certain phase of remission, having adequate organ function, and not having had certain previous treatments like stem cell transplants within the last year.

Inclusion Criteria

I have a high-risk form of MDS or MPD.

My Non-Hodgkin lymphoma is at high risk of getting worse if not in remission.

My organs are functioning well and I can do most activities.

Exclusion Criteria

I have been diagnosed with myelofibrosis or another cancer that affects my bone marrow.

My brain or spinal cord cancer is still visible on scans.

I had a stem cell transplant from my own cells within the last year.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Treatment

Participants receive standard chemotherapy and total body irradiation therapy to prepare for the transplant

1-2 weeks

Transplantation

Infusion of the double-unit cord blood graft

1 day

Inpatient stay for transplantation

Post-Transplant Monitoring

Participants are monitored for side effects, disease relapse, GVHD, and immune system recovery

Up to 45 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

• Conditioning Chemotherapy (Chemotherapy)
• Cord blood graft (Stem Cell Transplant)

Trial Overview The study tests an 'optimized' cord blood transplant (CBT) process developed by MSK. It includes evaluation methods, conditioning chemotherapy, total body irradiation before the transplant, and post-transplant care to assess side effects, disease relapse rates, graft-versus-host disease (GVHD), and immune recovery.

Participant Groups

Group I: Cord Blood Transplant Experimental Treatment 2 Interventions

Adult patients with high-risk hematologic malignancies and a suitable double-unit CB graft will undergo work-up to assess protocol eligibility. CB graft selection will be based on established MSKCC guidelines. Patients will receive standard conditioning with Cy 50 mg/kg, Flu 150 mg/m2, Thio 10 mg/kg, and TBI 400 cGy according to the eligibility criteria. GVHD prophylaxis will consist of CSA and MMF starting day -3. The double-unit CB graft will be infused on day 0 per standard practice. Optimized CBT practices, will be implemented in this protocol.

Conditioning Chemotherapy is already approved in Canada, Japan, China, Switzerland for the following indications:

Approved in Canada as Chemotherapy for:

• Blood cancers
• Leukemia
• Lymphoma
• Multiple myeloma

Approved in Japan as Chemotherapy for:

• Blood cancers
• Leukemia
• Lymphoma
• Multiple myeloma

Approved in China as Chemotherapy for:

• Blood cancers
• Leukemia
• Lymphoma
• Multiple myeloma

Approved in Switzerland as Chemotherapy for:

• Blood cancers
• Leukemia
• Lymphoma
• Multiple myeloma

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Lisa M. DeAngelis

Memorial Sloan Kettering Cancer Center

Chief Medical Officer since 2021

MD from Columbia University

Selwyn M. Vickers

Memorial Sloan Kettering Cancer Center

Chief Executive Officer since 2022

MD from Johns Hopkins University

Findings from Research

Umbilical cord blood transplantation (UCBT) using an improved myeloablative conditioning regimen (TBI/Ara-c/CY) resulted in 100% engraftment among 40 adult patients with hematological malignancies, demonstrating its efficacy in establishing donor cell engraftment.

The treatment showed a two-year overall survival rate of 58.8%, with lower relapse rates and chronic graft-versus-host disease (GVHD) occurrences in high-risk and advanced patients, indicating a favorable safety profile and potential benefits for these challenging cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Unrelated umbilical cord blood transplantation with TBI/Ara-c/CY non-ATG conditioning regimen for adults with hematologic malignancies]. Sun, ZM., Liu, HL., Geng, LQ., et al.[2012]

Umbilical cord blood (CB) transplantation offers significant advantages over traditional bone marrow transplantation, including better matching, quicker availability, and reduced risk of graft-versus-host disease, making it a promising option for patients with hematological malignancies.

CB-derived T cells can be expanded and modified for enhanced immunotherapy, and combining these with vaccination strategies may lead to more effective treatments against tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of cord blood derived T-cells in cancer immunotherapy: milestones achieved and future perspectives. Lo Presti, V., Nierkens, S., Boelens, JJ., et al.[2019]

Umbilical cord blood transplantation (CBT) has seen significant advancements over the past 20 years, improving myeloid and platelet engraftment rates, particularly through strategies like double CBT and ex-vivo graft engineering.

Despite these improvements, delayed immune reconstitution remains a major challenge, especially in adult recipients, leading to increased risks of infections; ongoing research is focused on enhancing T cell recovery and preserving thymopoiesis to further improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cord blood transplantation: evolving strategies to improve engraftment and immune reconstitution. Escalón, MP., Komanduri, KV.[2019]

In a study of 71 children with acute leukemia undergoing cord blood transplantation, those who received the TCF conditioning regimen (total body irradiation, cyclophosphamide, and fludarabine) had a 100% engraftment rate, compared to only 77.4% in the non-TCF group.

The TCF group also experienced significantly lower rates of cytomegalovirus disease (5.6% vs. 30.2%) and had a higher 5-year overall survival rate of 77.8%, compared to 44.2% in the non-TCF group, indicating that the TCF regimen is more effective and safer for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conditioning with 10 Gy Total Body Irradiation, Cyclophosphamide, and Fludarabine without ATG Is Associated with Improved Outcome of Cord Blood Transplantation in Children with Acute Leukemia. Cho, HW., Ju, HY., Hyun, JK., et al.[2021]

Umbilical cord blood (CB) is increasingly used for hematopoietic cell transplants in patients with high-risk blood disorders, showing decreased relapse rates compared to other donor sources, although it may lead to higher transplantation-related mortality.

The use of double CB units has effectively addressed the dose limitations of single units, allowing for successful transplants in larger children and adults, while reduced intensity conditioning has made it possible to treat older patients who cannot handle more aggressive treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Umbilical cord blood transplantation: a maturing technology. Oran, B., Shpall, E.[2016]

In a study involving 25 patients with refractory cancers, low-dose total body irradiation (100 cGy) followed by allogeneic stem cell transplantation showed promising results, particularly in hematologic malignancies, where 9 out of 11 patients achieved donor chimerism.

Among the patients with hematologic cancers, 4 achieved sustained complete remission, indicating that this approach may be effective and less toxic compared to conventional high-dose conditioning regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose total body irradiation followed by allogeneic lymphocyte infusion for refractory hematologic malignancy--an updated review. Ballen, KK., Colvin, G., Porter, D., et al.[2019]

Hematopoietic stem cell transplants have become more common and effective due to advances in technology, with peripheral blood stem cells now preferred over bone marrow for autologous transplants, and non-myeloablative conditioning regimens being explored to reduce toxicity.

Despite improvements in safety and supportive care, stem cell transplants still carry risks of complications, making proactive assessment and management of potential side effects crucial for successful outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Managing the toxicity of hematopoietic stem cell transplant. Pallera, AM., Schwartzberg, LS.[2005]

High-dose conditioning agents used before hemopoietic stem cell transplants can lead to significant procedure-related mortality (10-30%), prompting research into low-dose alternatives to reduce risks.

New low-toxicity conditioning agents, such as radiolabeled immunoglobulins, show promise in improving the safety and efficacy of stem cell transplants by targeting only the necessary tissues, potentially increasing the therapeutic index.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aims of conditioning. Vriesendorp, HM.[2019]

A new reduced-intensity conditioning regimen (Flu/MEL/LD-rATG) for umbilical cord blood transplantation achieved a 100% engraftment rate and a 5-year event-free survival rate of 90.9% in 11 children, indicating its high efficacy.

This regimen outperformed previous conditioning methods that included irradiation, which had a significantly lower 5-year event-free survival rate of 30.0%, suggesting that the new approach is safer and more effective for treating rare hematological disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children. Sawada, A., Shimizu, M., Koyama-Sato, M., et al.[2022]

Chemotherapy patients commonly face complications like neutropenia, fever, and infections, but the use of antibodies, antimycotics, and G-CSF can help manage these risks effectively.

Nausea and vomiting from chemotherapy can often be prevented with proper antiemetic treatments, while anemia can be treated with red cell concentrates and erythropoietin, highlighting the importance of supportive care in managing chemotherapy side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Patient treated with chemotherapy. Alarm signs requiring immediate intervention]. Mende, S.[2006]

The pilot study involving 17 adult patients with advanced hematologic malignancies demonstrated the feasibility of reduced-intensity cord blood transplantation (RI-CBT) using a non-total body irradiation (TBI) regimen, with 9 out of 13 evaluable patients achieving successful engraftment.

Among the patients who achieved engraftment, 6 were alive in remission at a median follow-up of 13.1 months, suggesting that RI-CBT can provide a clinically significant graft-vs-tumor effect when disease progression is managed effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan. Komatsu, T., Narimatsu, H., Yoshimi, A., et al.[2013]

In a study of 171 adults with hematologic malignancies, unrelated cord blood transplantation (CBT) showed similar overall engraftment rates compared to related donor transplants, despite a significant delay in engraftment after CBT.

CBT recipients experienced significantly lower rates of severe acute and chronic graft-versus-host disease (GVHD) and had comparable transplantation-related mortality, relapse rates, and disease-free survival compared to those receiving related bone marrow or peripheral blood stem-cell transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. Takahashi, S., Ooi, J., Tomonari, A., et al.[2021]

Cord blood stem cell transplantation (CBST) has been successfully performed in over 300 patients, showing a probability of event-free survival comparable to traditional bone marrow transplantation (BMT).

CBST may provide a solution to the challenges of finding suitable donors and reducing the risk of severe graft-versus-host disease (GVH), making it a promising alternative for treating hematologic and solid malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Present state of cord-blood stem cell transplantation]. Nishihira, H., Ohnuma, K., Toyoda, Y.[2007]

Umbilical cord blood transplantation serves as a crucial alternative for patients lacking matched adult donors, especially benefiting those from diverse ethnic backgrounds who face challenges in finding suitable donors.

This method has led to over 25,000 patients being cured, highlighting its efficacy as a curative treatment for various blood-related diseases and genetic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on umbilical cord blood transplantation. Ballen, K.[2019]

References

1. China pubmed.ncbi.nlm.nih.gov

[Unrelated umbilical cord blood transplantation with TBI/Ara-c/CY non-ATG conditioning regimen for adults with hematologic malignancies]. [2012]

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

Use of cord blood derived T-cells in cancer immunotherapy: milestones achieved and future perspectives. [2019]

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

Cord blood transplantation: evolving strategies to improve engraftment and immune reconstitution. [2019]

4. Korea (South) pubmed.ncbi.nlm.nih.gov

Conditioning with 10 Gy Total Body Irradiation, Cyclophosphamide, and Fludarabine without ATG Is Associated with Improved Outcome of Cord Blood Transplantation in Children with Acute Leukemia. [2021]

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

Umbilical cord blood transplantation: a maturing technology. [2016]

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

Low dose total body irradiation followed by allogeneic lymphocyte infusion for refractory hematologic malignancy--an updated review. [2019]

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

Managing the toxicity of hematopoietic stem cell transplant. [2005]

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

Aims of conditioning. [2019]

9. Japan pubmed.ncbi.nlm.nih.gov

Radiation-sparing reduced-intensity unrelated umbilical cord blood transplantation for rare hematological disorders in children. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

[Patient treated with chemotherapy. Alarm signs requiring immediate intervention]. [2006]

11. Germany pubmed.ncbi.nlm.nih.gov

Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan. [2013]

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

Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen. [2021]

13. Japan pubmed.ncbi.nlm.nih.gov

[Present state of cord-blood stem cell transplantation]. [2007]

14. England pubmed.ncbi.nlm.nih.gov

Update on umbilical cord blood transplantation. [2019]