Cord Blood Transplant for Leukemia

Overseen By Claudio Brunstein, MD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Pregnant, HIV positive, others

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

Compensation: Varies

Number of Visits: Unknown

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment for various blood cancers, including acute leukemias, using umbilical cord blood transplants. The goal is to determine the effectiveness of a combination of drugs and radiation in preparing the body for the transplant. These treatments, including Cyclophosphamide (a chemotherapy drug), Fludarabine (another chemotherapy drug), and Total Body Irradiation (a form of radiation therapy), aim to destroy diseased cells and promote the growth of new, healthy cells. Eligible participants have blood cancers like acute leukemia or chronic myelogenous leukemia and have undergone previous treatments but still require additional help. Participants should also have access to suitable cord blood and be willing to provide written consent. As an unphased trial, this study offers the opportunity to contribute to groundbreaking research that could improve future treatments for blood cancer patients.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since this is a transplant procedure, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

What prior data suggests that this treatment guideline is safe for umbilical cord blood transplant?

Research has shown that using cyclophosphamide, fludarabine, and total body irradiation (TBI) in umbilical cord blood transplants (UCBT) has been tested in earlier studies. These treatments are generally well-tolerated. For example, one study found that fludarabine and TBI were well-tolerated even when the donor was not a perfect match, suggesting the treatment is relatively safe for humans.

While side effects can occur, these studies provide some reassurance about its safety. Cyclophosphamide, fludarabine, and TBI are already used in other approved treatments, which adds to the confidence in their safety. It is important to consult a healthcare provider to understand the potential risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using umbilical cord blood transplants for leukemia because this treatment offers a unique approach compared to standard treatments like chemotherapy and bone marrow transplants. Unlike bone marrow transplants, which require a close donor match, umbilical cord blood transplants can be more easily matched to patients, potentially increasing accessibility for those in urgent need of a transplant. Additionally, cord blood contains young, adaptable stem cells that may lead to fewer complications and a quicker recovery. This approach combines powerful radiation and chemotherapy to prepare the body, followed by the infusion of cord blood, which is thought to be more adaptable and less likely to provoke severe immune reactions.

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

Research has shown that umbilical cord blood transplants can effectively treat blood cancers like acute leukemias. In one study, 81% of patients survived two years after receiving this treatment. Another study found that many patients remained free of leukemia for an extended period, indicating lasting benefits. This trial will evaluate the effectiveness of an umbilical cord blood transplant following a myeloablative preparative regimen consisting of Cyclophosphamide, Fludarabine, and Total Body Irradiation. This treatment works well for both children and young adults with acute leukemia and is widely accepted by doctors for these conditions. ^{2 6 7 8 9}

Who Is on the Research Team?

Claudio Brunstein, MD

Principal Investigator

University of Minnesota

Are You a Good Fit for This Trial?

This trial is for people aged 0-55 with certain blood diseases like leukemia, lymphoma, and myeloma. They should be in specific stages of the disease and have responded to initial treatments. Participants must consent to join. It's not for those who've had recent transplants, are pregnant or breastfeeding, HIV positive, or have had extensive prior therapy.

Inclusion Criteria

My initial cancer treatment has been effective.

I am between 0 and 55 years old.

I have a specific type or stage of blood cancer.

Exclusion Criteria

I am HIV positive.

My large cell or high grade NHL cancer did not respond to more than 2 treatments.

I've had extensive cancer treatment, including long-term alkylator therapy or radiation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparative Regimen

Participants undergo a myeloablative preparative regimen consisting of cyclophosphamide, fludarabine, and fractionated total body irradiation

1-2 weeks

Umbilical Cord Blood Transplantation

Participants receive an umbilical cord blood transplant followed by administration of immunosuppressive Cyclosporine and Mycophenylate Mofetil

1 week

Follow-up

Participants are monitored for survival, engraftment, and incidence of graft versus host disease

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Fludarabine
• Total Body Irradiation

Trial Overview The study tests an umbilical cord blood transplant using a strong chemotherapy regimen (cyclophosphamide and fludarabine) plus total body irradiation as treatment for various hematological diseases. The goal is to see how well this combination works in patients with these conditions.

How Is the Trial Designed?

Group I: Umbilical Cord Blood Transplant Experimental Treatment 6 Interventions

The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI)followed by umbilical cord blood transplant. Immunosuppressive Cyclosporine and Mycophenylate Mofetil (MMF) will be administered pre- and post UCBT.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Published Research Related to This Trial

In a phase I study involving 9 patients with advanced hematological malignancies, the combination of cytosine arabinoside (Ara-C) and cyclophosphamide (CY) with total body irradiation (TBI) resulted in severe toxicity, with multiple patients experiencing fatal outcomes at higher doses.

The study concluded that the concurrent administration of Ara-C and CY may not be suitable for phase I trials due to the high risk of severe, dose-independent toxicity, highlighting the need for caution in developing such treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous infusion of high-dose cytosine arabinoside with cyclophosphamide followed by total body irradiation and marrow infusion for the treatment of patients with advanced hematological malignancy. Petersen, FB., Appelbaum, FR., Buckner, CD., et al.[2016]

In a study of 26 pediatric patients with Fanconi anemia undergoing stem cell transplantation, a conditioning regimen of low-dose cyclophosphamide, fludarabine, and antithymocyte globulin was well tolerated, showing low rates of complications like graft-versus-host disease and hemorrhagic cystitis.

All patients receiving HLA-matched related donor transplants successfully engrafted and remained alive and transfusion-independent after a median follow-up of 19 months, highlighting the regimen's effectiveness, especially in matched donor scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Saudi experience in fludarabine-based conditioning regimens in patients with Fanconi anemia undergoing stem cell transplantation: excellent outcome in recipients of matched related stem cells but not in recipients of unrelated cord blood stem cells. Ayas, M., Al-Seraihi, A., El-Solh, H., et al.[2013]

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 three children with refractory severe aplastic anemia (SAA), a radiotherapy-free conditioning regimen using fludarabine and other agents was effective in preparing them for hemopoietic cell transplantation (HCT) without the development of graft-versus-host disease (GVHD).

All patients achieved normal blood counts and complete donor chimerism after the transplant, demonstrating that fludarabine-based conditioning can be a safe and effective option for children undergoing HCT from alternative donors, even after previous transplant failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-radiotherapy conditioning with stem cell transplantation from alternative donors in children with refractory severe aplastic anemia. Urban, C., Benesch, M., Sykora, KW., et al.[2013]

In a study of 38 patients with hematologic malignancies undergoing single-unit cord blood transplantation, the conditioning regimen of total-body irradiation (TBI) combined with FLAG chemotherapy resulted in a high donor engraftment rate of 97%.

The regimen was well tolerated, with a median follow-up of 46 months showing a 3-year event-free survival rate of 33.5%, significantly higher in the standard-risk group (72.7%) compared to the high-risk group (17.7%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unrelated umbilical cord blood transplantation using a TBI/FLAG conditioning regimen for adults with hematologic malignancies. Okada, M., Fujimori, Y., Misawa, M., et al.[2013]

In a study of 85 patients with hematological malignancies, adding fludarabine to a 2-Gy total body irradiation (TBI) regimen before stem cell transplantation resulted in better overall survival (65% vs. 54%) and lower relapse rates compared to TBI alone.

The combination of fludarabine and TBI led to significantly higher levels of donor T cell and NK cell chimerism, indicating improved donor engraftment and a stronger graft-versus-tumor effect, which is crucial for successful transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine and 2-Gy TBI is superior to 2 Gy TBI as conditioning for HLA-matched related hematopoietic cell transplantation: a phase III randomized trial. Kornblit, B., Maloney, DG., Storb, R., et al.[2021]

A modified myeloablative regimen using thiotepa, TBI, and fludarabine in 31 adult patients resulted in a high neutrophil engraftment rate of 90% by 60 days, indicating improved engraftment while reducing treatment-related mortality (TRM) to 30% at 3 years.

The study also reported manageable rates of acute and chronic graft-versus-host disease (GVHD), with 45% experiencing grades II to IV acute GVHD by day 100 and 40% developing chronic GVHD by 2 years, suggesting that this regimen is a promising alternative for umbilical cord blood transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult Umbilical Cord Blood Transplantation Using Myeloablative Thiotepa, Total Body Irradiation, and Fludarabine Conditioning. Anand, S., Thomas, S., Corbet, K., et al.[2018]

Fludarabine phosphate, an antimetabolite derived from adenosine arabinoside, has been found to be safe at a dose of 20 mg/m2 administered every 12 hours for 6 doses in good-risk patients during a phase I trial.

The main side effect of fludarabine phosphate is myelosuppression, which can become severe at higher doses, highlighting the need for careful dose management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of fludarabine (2-fluoro-ara-AMP). Kavanagh, JJ., Krakoff, IH., Bodey, GP.[2019]

In a study of 89 hematopoietic cell transplantation recipients, higher levels of the active metabolite of cyclophosphamide (PM AUC0-8 hr) were linked to worse nonrelapse mortality and overall survival, indicating that careful monitoring of this metabolite is crucial for patient outcomes.

Patients with low levels of the active metabolite of fludarabine (F-ara-ADay-4) and low PM AUC0-8 hr had significantly lower nonrelapse mortality, suggesting that optimizing drug exposure could improve safety and efficacy in reduced-intensity conditioning regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher Fludarabine and Cyclophosphamide Exposures Lead to Worse Outcomes in Reduced-Intensity Conditioning Hematopoietic Cell Transplantation for Adult Hematologic Malignancy. Takahashi, T., Scheibner, A., Cao, Q., et al.[2021]

The addition of 9 Gy of total body irradiation (TBI) to a reduced intensity regimen of fludarabine and melphalan in pediatric patients with advanced hematologic malignancies resulted in successful neutrophil and platelet engraftment, with 27 patients achieving neutrophil engraftment by a median of 16 days.

Despite some toxicities like oral mucositis and diarrhea, the treatment was generally well tolerated, and with a median follow-up of 52 months, 7 out of 22 patients with acute lymphoblastic leukemia (ALL) and 5 out of 6 patients with acute myeloid leukemia (AML) remained alive and in remission, indicating potential efficacy that warrants further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Total body irradiation, fludarabine, melphalan, and allogeneic hematopoietic stem cell transplantation for advanced pediatric hematologic malignancies. Petropoulos, D., Worth, LL., Mullen, CA., et al.[2013]

In a study of 2,255 adult patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic cell transplantation, conditioning with total body irradiation (TBI) plus cyclophosphamide (Cy) significantly reduced the risk of relapse compared to TBI plus fludarabine (Flu), with a relapse rate of 18% versus 30% at 2 years.

While TBI/Cy was associated with a higher risk of grade 2-4 acute graft-versus-host disease (GVHD), it did not significantly affect other transplantation outcomes, suggesting that TBI/Cy may be a preferable conditioning regimen for patients in complete remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine or cyclophosphamide in combination with total body irradiation as myeloablative conditioning prior to allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia: an analysis by the Acute Leukemia Working Party of the EBMT. Giebel, S., Labopin, M., Socié, G., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3943318/

Cost-effectiveness and clinical outcomes of double versus ... The overall survival at 2 years after single and double cord blood transplants was 42% versus 62%, respectively (P=0.03), while the leukemia-free-survival was ...

2. cancernetwork.com cancernetwork.com/view/ucbt-yields-excellent-efficacy-outcomes-in-hematologic-malignancies

UCBT Yields Excellent Efficacy Outcomes in Hematologic ... The 2-year OS rate was 81% (95% CI, 69%-89%), and the 2-year PFS rate was 78% (65%-86%). Additionally, the 2-year relapse and NRM rates were 13% ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212624000833

Single vs double umbilical cord blood transplantation in ... Single & double umbilical cord transplants showed similar rates of chronic GVHD, mortality & leukemia-free survival . The study concludes that both single and ...

4. nature.com nature.com/articles/s41409-025-02508-2

Myeloablative conditioning in cord blood transplantation for ... Umbilical cord blood transplantation (CBT) is accepted as an effective treatment for acute myeloid leukemia (AML), and reduced-intensity ...

5. astctjournal.org astctjournal.org/article/S1083-8791(18)30649-9/fulltext

Single-Unit versus Double-Unit Umbilical Cord Blood ... Umbilical cord blood transplantation (UCBT) offers high survival rates in children and young adults with acute leukemia.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00719888?cond=%22Macroglobulinemia%22&intr=%22Cyclosporine%22&viewType=Table&rank=3

Study Details | Umbilical Cord Blood Transplant ... This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide, fludarabine, and total-body irradiation (TBI) ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3673764/

A Novel Reduced Intensity Conditioning Regimen Induces a ... We used the cyclophosphamide, fludarabine, total body irradiation (TBI) 200 ... leukemia outcomes after umbilical cord blood transplantation. Biol ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-05598

Cord Blood Transplant, Cyclophosphamide, Fludarabine ... This phase II trial studies how well giving an umbilical cord blood transplant together with cyclophosphamide, fludarabine, and total-body irradiation (TBI) ...

9. astctjournal.org astctjournal.org/article/S2666-6367(24)00585-2/fulltext

Total Body Irradiation and Fludarabine with Post- ... 008). In conclusion, fludarabine/fTBI with PTCy was well-tolerated in mismatched donor HCT, regardless of donor relationship to the patient, ...