Cord Blood Transplant for Blood Diseases

Overseen By Omar Aljitawi, MD

Age: Any Age

Sex: Any

Trial Phase: Academic

Sponsor: University of Rochester

Disqualifiers: Pregnancy, HIV, Uncontrolled infection, others

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

Compensation: Varies

Number of Visits: 30

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of umbilical cord blood transplants in treating various blood diseases. Researchers aim to determine how quickly the transplanted stem cells aid in blood cell count recovery and the frequency of transplant failure. They also study the likelihood of remaining disease-free, the risk of disease recurrence, and complications such as graft versus host disease, where transplanted white blood cells attack the body. This trial may suit individuals with certain blood diseases or immune disorders who have not found success with other treatments. As a Phase 3 trial, this treatment represents the final step before FDA approval, offering participants access to potentially groundbreaking therapy.

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 trial's treatments are likely to be safe?

Research has shown that each treatment in this study has been tested before, providing information about their safety.

For the Busulfan-Cyclophosphamide-Cord Blood Infusion regimen, studies have examined side effects. While some side effects are expected, they are typical for stem cell transplants. Monitoring for complications is important, but this combination has been used in similar treatments, indicating some understanding of its safety.

The TBI-Cyclophosphamide-Cord Blood Infusion treatment has also undergone study. Total body irradiation (TBI), part of this regimen, can increase the risk of future cancers, but it is generally well-tolerated when combined with drugs like cyclophosphamide.

Research has shown that the Fludarabine-Cyclophosphamide-TBI-Cord Blood Infusion is well-tolerated in patients with mismatched donors. This suggests the treatment is relatively safe, though monitoring remains necessary.

Lastly, the Fludarabine-Melphalan-Cord Blood Infusion has been studied for safety and practicality. It is considered a practical option, with earlier studies noting manageable side effects.

Overall, these treatments are not new in clinical settings, and previous studies provide insight into potential risks. However, individual responses can vary, and participants receive close monitoring for safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for blood diseases because they explore the potential of cord blood transplants with various conditioning regimens that could offer new hope to patients. Unlike traditional bone marrow transplants that require finding a perfect donor match, cord blood transplants can be more accessible due to less stringent matching requirements. The various regimens, like full intensity chemo-based, TBI-based conditioning, and non-myeloablative conditioning, allow for tailored approaches depending on the patient's needs and health status, potentially reducing side effects and improving outcomes. Additionally, the inclusion of drugs like Busulfan, Cyclophosphamide, Fludarabine, and Melphalan, and the use of Total Body Irradiation provide flexibility in preparing the body to accept the transplant, which could lead to better long-term success rates compared to current standards.

What evidence suggests that this trial's treatments could be effective for blood diseases?

Research has shown that umbilical cord blood transplants can effectively treat blood diseases. In this trial, participants may receive different treatment regimens. One arm uses busulfan and cyclophosphamide with cord blood; studies have indicated that 88% of patients survive at least five years after treatment. Another arm includes total body irradiation (TBI) and cyclophosphamide with cord blood, which has been well-tolerated and suggests potential effectiveness. Additionally, some participants will receive fludarabine and melphalan with cord blood, which improved survival rates in older patients. Overall, these treatments show promise in helping patients with blood diseases live longer. ^{3 6 7 8 9}

Who Is on the Research Team?

Omar Aljitawi, MD

Principal Investigator

Professor - Department of Medicine, Hematology/Oncology (SMD)

Are You a Good Fit for This Trial?

This trial is for patients with various blood diseases, immune disorders, and cancers like leukemia, lymphoma, and solid tumors. Participants need to have a certain level of physical fitness (Karnofsky or Lansky score ≥ 70%) and good heart, lung, kidney, and liver function. They must not be pregnant or breastfeeding, HIV positive, or have had a recent autologous HSCT. A suitable HLA-matched donor should not be available.

Inclusion Criteria

My condition is one of the listed blood disorders or cancers.

I am mostly able to care for myself but may not be able to do active work.

My heart, lungs, kidneys, and liver are all working well.

Exclusion Criteria

I had a stem cell transplant using my own cells less than 6 months ago.

Pregnant or breast feeding

You have been diagnosed with HIV or tested positive for HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-transplant Conditioning

Participants receive chemotherapy +/- total body radiation as a pre-transplant conditioning regimen

8 days

Daily visits for treatment administration

Transplantation

Participants receive cord blood stem cells followed by GvHD prophylaxis

1 day

Inpatient stay for transplantation

Follow-up

Participants are monitored for safety and effectiveness after transplantation

120 months

Regular visits at 30 days, 100 days, 6 months, and yearly

What Are the Treatments Tested in This Trial?

Interventions

• Busulfan
• Cord Blood Infusion
• Cyclophosphamide
• Fludarabine
• Melphalan
• Mesna
• Total Body Irradiation 1200 cGy
• Total Body Irradiation 200 cGy

Trial Overview The study tests umbilical cord blood stem cell transplantation using one of four preparative regimens that include Melphalan, Mesna, Fludarabine among others. It aims to validate the transplantation process at the institution conducting the research.

How Is the Trial Designed?

Group I: Reduced Intensity Chemotherapy Experimental Treatment 3 Interventions

Reduced Intensity Chemotherapy Fludarabine 30 mg/m2/day x 5 doses days -6 to -2 Melphalan 140 mg/m2/day x 1 dose day -2 Cord Blood Infusion Other names: Flu/Mel

Group II: Non-Myeloablative Conditioning Experimental Treatment 4 Interventions

Fludarabine 40 mg/m2/day x 5 doses days -6 to -2 Cyclophosphamide 50 mg/kg/day x 1 dose day -6 Mesna 50 mg/kg/day with 20% loading dose with Cyclophosphamide dose followed by continuous infusion over 24 hours x 1 dose \[to be completed 24 hours after Cyclophosphamide dose\] Total Body Irradiation 200 cGy in a single fraction day -1 Cord Blood Infusion Other names: Flu/Cy/TBI

Group III: Full Intensity, TBI-based Conditioning Experimental Treatment 4 Interventions

Full Intensity TBI-based Conditioning Total Body Irradiation 1200 cGy in fractions of 150 cGy days -8 or -7 to -4 Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses \[to be completed 24 hours after final Cyclophosphamide dose\] followed by Cord Blood Infusion Other names: TBI/Cy

Group IV: Full Intensity, Chemo-based Conditioning Experimental Treatment 4 Interventions

Full Intensity, Chemotherapy Conditioning Busulfan days -7 to -4 Recipients \<5 years - 1 mg/kg/dose x 16 doses every 6 hours Recipients \>/= 5 years - 0.8 mg/kg/dose x 16 doses every 6 hours Cyclophosphamide 60 mg/kg/day x 2 doses days -3 and -2 Mesna 60 mg/kg/day with 20% loading dose with first Cyclophosphamide followed by continuous infusion over 24 hours x 2 doses \[to be completed 24 hours after final Cyclophosphamide dose\] followed by Cord Blood Infusion Other names: Bu/Cy

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

Approved in United States as Busulfex for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Malignant lymphoma
• Bone marrow transplantation conditioning

Approved in European Union as Busulfan for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Approved in Canada as Busulfex for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Approved in Japan as Busulfan for:

• Chronic myeloid leukemia
• Acute myeloid leukemia
• Bone marrow transplantation conditioning

Who Is Running the Clinical Trial?

University of Rochester

Lead Sponsor

Trials

883

Recruited

555,000+

Published Research Related to This Trial

In a meta-analysis of 15 randomized controlled trials involving 10,160 pediatric patients, total body irradiation plus cyclophosphamide (TBI/CY) was found to be more effective than busulfan plus cyclophosphamide (BU/CY) in reducing transplant failure rates and improving long-term disease-free survival rates.

The TBI/CY regimen also demonstrated a lower incidence of adverse reactions compared to the BU/CY regimen, indicating it may be a safer option for pediatric hematopoietic stem cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two Different Transplant Preconditioning Regimens Combined with Irradiation and Chemotherapy in the Treatment of Childhood Leukemia: Systematic Review and Meta-Analysis. Wang, X., Mu, D., Geng, A., et al.[2023]

In a study involving 10 adult patients with myeloid malignancies, the combination of once-daily intravenous busulfan and fludarabine as a preparative regimen for umbilical cord blood transplantation resulted in donor-derived neutrophil recovery in only 2 out of 10 patients, indicating poor engraftment.

The findings suggest that this myeloablative conditioning regimen does not provide adequate immunosuppression for successful engraftment of partially matched dual umbilical cord blood grafts, leading to the premature closure of the study due to graft failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients. Horwitz, ME., Morris, A., Gasparetto, C., et al.[2021]

In a study evaluating three myeloablative regimens for cord blood transplantation in high-risk hematologic malignancies, the third regimen (busulfan, clofarabine, fludarabine, and low-dose total body irradiation) showed low engraftment failure and effective tumor control, suggesting it is a promising option.

While the first regimen led to quick engraftment, it had a high nonrelapse mortality rate, and the second regimen was well tolerated but resulted in high engraftment failure, highlighting the need for careful selection of preparative regimens in cord blood transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation. Mehta, RS., Di Stasi, A., Andersson, BS., et al.[2021]

In a study comparing two treatment regimens for children undergoing hematopoietic cell transplantation, the combination of fludarabine and busulfan (FluBu) showed similar survival rates to busulfan and cyclophosphamide (BuCy), with 2-year survival rates of 82% for FluBu and 78% for BuCy.

The FluBu regimen was associated with significantly lower toxicity, including reduced rates of lung injury, veno-occlusive disease, and infections, as well as a shorter duration of neutropenia, indicating it may be a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: maintaining efficacy with less toxicity. Bartelink, IH., van Reij, EM., Gerhardt, CE., et al.[2014]

In a study of 333 adult patients undergoing cord blood transplantation, there were no significant differences in key outcomes such as neutrophil recovery, graft-versus-host disease, or overall survival between those receiving total body irradiation (TBI)-based and busulfan-based myeloablative conditioning regimens.

However, TBI-based regimens showed better survival rates specifically for patients with acute lymphoblastic leukemia, suggesting that the choice of conditioning regimen may impact outcomes based on the type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total body irradiation-based versus busulfan-based myeloablative conditioning for single-unit cord blood transplantation in adults. Konuma, T., Ooi, J., Monna-Oiwa, M., et al.[2022]

In a study of 43 children with acute lymphoblastic leukemia (ALL) undergoing allogeneic stem cell transplant, those receiving total body irradiation (TBI) had a significantly better event-free survival (EFS) rate of 58% compared to 29% for those receiving busulfan (Bu) after a median follow-up of 43 months.

The results indicate that busulfan is less effective than TBI, particularly for patients receiving stem cells from unrelated donors, where EFS was only 20% for Bu compared to 57% for TBI, suggesting that TBI may be the preferred conditioning regimen for pediatric ALL patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized trial of busulfan vs total body irradiation containing conditioning regimens for children with acute lymphoblastic leukemia: a Pediatric Blood and Marrow Transplant Consortium study. Bunin, N., Aplenc, R., Kamani, N., et al.[2013]

A conditioning regimen using melphalan, thiotepa, fludarabine, and rabbit antithymocyte globulin (FMT) was evaluated in 47 patients with advanced hematologic malignancies, showing that 91% of patients successfully engrafted neutrophils after a median of 22 days, indicating effective hematopoietic recovery.

Despite a significant incidence of grade 3 gastrointestinal toxicity (32%) and a cumulative incidence of acute and chronic graft-versus-host disease (53% and 34%, respectively), the two-year disease-free survival rate was 31% and overall survival rate was 44%, suggesting that FMT is a feasible and potentially effective conditioning regimen for unrelated cord blood transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine, melphalan, thiotepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant. Ciurea, SO., Saliba, RM., Hamerschlak, N., et al.[2021]

This study is a multicenter, open-label, randomized phase III trial designed to evaluate the effectiveness of adding granulocyte-colony stimulating factor (G-CSF) to a conditioning regimen of high-dose cytosine arabinoside (CA) and cyclophosphamide/total body irradiation (CY/TBI) for umbilical cord blood transplantation (CBT) in patients aged 16-55 with acute myeloid leukemia or myelodysplastic syndrome, with a target sample size of 160 participants.

The primary goal is to assess the 2-year disease-free survival rate after CBT, while secondary outcomes include overall survival, relapse rates, and various complications, aiming to determine if G-CSF improves outcomes compared to standard conditioning without G-CSF.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised controlled trial of conditioning regimen for cord blood transplantation for adult myeloid malignancies comparing high-dose cytarabine/cyclophosphamide/total body irradiation with versus without G-CSF priming: G-CONCORD study protocol. Terakura, S., Konuma, T., Tanaka, M., et al.[2021]

A conditioning regimen of busulfan, fludarabine, and melphalan was safely administered to 6 patients aged 1 to 19 years with very high-risk myeloid malignancies, resulting in complete donor engraftment even with small umbilical cord blood grafts.

All patients remained in remission without experiencing acute or chronic graft-versus-host disease during a median follow-up of 24 months, suggesting strong disease control and safety of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alternative Donor Hematopoietic Cell Transplantation Conditioned With Myeloablative Busulfan, Fludarabine, and Melphalan is Well Tolerated and Effective Against High-risk Myeloid Malignancies. Katsanis, E., Sapp, LN., Pelayo-Katsanis, L., et al.[2022]

A pilot study involving 30 pediatric patients with high-risk solid tumors demonstrated that high-dose busulfan/melphalan conditioning therapy before autologous stem cell transplantation is feasible and generally well-tolerated, with a treatment-related mortality rate of 6.6%.

After a median follow-up of 18 months, 19 out of 30 patients were alive and disease-free, indicating a promising 4-year event-free survival rate of 55%, showcasing the therapy's potential antitumor efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose busulfan/melphalan as conditioning for autologous PBPC transplantation in pediatric patients with solid tumors. Diaz, MA., Vicent, MG., Madero, L.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11757842/

Comparing haploidentical transplantation with post- ... The 5-year event-free and overall survival rates were 65.8% and 54.2% (p = 0.204) and 78.0% and 65.7% (p = 0.142) for the HRD and UCB groups, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01247701

Umbilical Cord Blood Transplant for Children With Myeloid ... In this study, the investigators will use busulfan and cyclophosphamide (BuCy) backbone with the addition of fludarabine as the preparative Stem Cell ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1083879120305826

Outcome After Cord Blood Transplantation Using Busulfan ... Five-year overall survival (OS) and engrafted survival (ES) were 88% and 79%, respectively. OS was 95% in patients who received Bu/fludarabine (Flu)/ ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4261695/

Busulfan in Hematopoietic Stem Cell Transplantation - PMC In particular, their engraftment rate of more than 90% and a 10-year DFS of 60% in a subpopulation of patients who received a single cord blood transplant for ...

5. astctjournal.org astctjournal.org/article/S1083-8791(20)30582-6/pdf

Outcome After Cord Blood Transplantation Using Busulfan ... Outcomes of interest were OS, engrafted survival (ES), graft failure, graft-versus-host disease. (GVHD), latest donor chimerism, and IDUA enzyme level. OS was.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8408385/

Adverse Effects of Busulfan Plus Cyclophosphamide ... In this study, we aimed to investigate the side effect of Bu/Cy and Bu/Flu regimens on our patients who underwent allogeneic bone marrow transplantation.

7. astctjournal.org astctjournal.org/article/S2666-6367(25)01408-3/fulltext

Efficacy and Safety of Haploidentical Hematopoietic Stem ... This study aimed to evaluate the efficacy and safety of combining UCB infusion with haplo-HSCT using older (≥40 years) haploidentical donors in ...

8. ashpublications.org ashpublications.org/bloodadvances/article/3/14/2057/260113/Safety-and-feasibility-of-virus-specific-T-cells

Safety and feasibility of virus-specific T cells derived from ... Key Points. CB-VSTs can be feasibly generated and are safe.CB-VSTs persist long term after infusion in CBT recipients.

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39847190/

Comparing haploidentical transplantation with post- ... These findings indicate that HRD HSCT with post-transplant cyclophosphamide provides promising outcomes compared to UCB HSCT in pediatric patients.