Cord Blood Transplant for Blood Diseases

Recruiting in Palo Alto (17 mi)

Overseen by Omar Aljitawi, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Rochester

Disqualifiers: Pregnancy, HIV, Uncontrolled infection, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial uses stem cells from a baby's umbilical cord to treat patients who need new healthy stem cells. Patients first get strong medicine to clear out unhealthy cells, then receive the new stem cells, and take medications to prevent complications. Umbilical cord blood has been used in the treatment of various diseases, including leukemias, lymphomas, and immune system disorders.

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 Diseases?

The study on high-dose busulfan/melphalan for autologous transplantation in children with solid tumors showed that this combination is feasible and well-tolerated, with an acceptable mortality rate and proven antitumor activity, suggesting potential effectiveness in similar transplant settings. ^{1 2 3 4 5}

Is cord blood transplant generally safe for treating blood diseases?

Research shows that using busulfan, fludarabine, and melphalan in cord blood transplants is generally well-tolerated, with acceptable safety profiles in both children and adults. Some studies report manageable side effects like gastrointestinal issues and rare serious complications, but overall, these regimens have been used safely in various conditions. ^{2 3 5 6 7}

How does the cord blood transplant treatment differ from other treatments for blood diseases?

This treatment is unique because it combines multiple chemotherapy drugs and total body irradiation to prepare the body for a cord blood transplant, which can be an alternative for patients without a matched donor. The combination of drugs like busulfan, fludarabine, and melphalan, along with total body irradiation, aims to reduce the risk of graft failure and relapse, although it may have higher toxicity compared to other regimens. ^{3 5 8 9 10}

Research Team

Omar Aljitawi, MD

Principal Investigator

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

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Busulfan (Alkylating agents)
• Cord Blood Infusion (Procedure)
• Cyclophosphamide (Alkylating agents)
• Fludarabine (Antimetabolites)
• Melphalan (Alkylating agents)
• Mesna (Antidotes)
• Total Body Irradiation 1200 cGy (Radiation)
• Total Body Irradiation 200 cGy (Radiation)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Kevin Koch

University of Rochester

Chief Executive Officer since 2020

PhD in Organic Chemistry from the University of Rochester

Brian Druker

University of Rochester

Chief Medical Officer since 2015

MD from Harvard Medical School

Findings from Research

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]

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]

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 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]

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 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]

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 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]

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]

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]

References

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

Total body irradiation-based versus busulfan-based myeloablative conditioning for single-unit cord blood transplantation in adults. [2022]

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

High-dose busulfan/melphalan as conditioning for autologous PBPC transplantation in pediatric patients with solid tumors. [2013]

3. England 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. [2023]

4. England 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. [2013]

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

Myeloablative intravenous busulfan/fludarabine conditioning does not facilitate reliable engraftment of dual umbilical cord blood grafts in adult recipients. [2021]

6. United States 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. [2014]

7. United States 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. [2022]

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

Fludarabine, melphalan, thiotepa and anti-thymocyte globulin conditioning for unrelated cord blood transplant. [2021]

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

The development of a myeloablative, reduced-toxicity, conditioning regimen for cord blood transplantation. [2021]

10. England 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. [2021]