Stem Cell Transplant for Infant Leukemia

Overseen By Christen Ebens, MD

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Active infection, HIV, Myeloablative transplant, others

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a combination of chemotherapy followed by a donor umbilical cord blood transplant can effectively treat infants with high-risk leukemia or myelodysplastic syndromes. Researchers aim to determine if this approach can help the patient's body produce healthy blood cells and combat the disease. The trial also examines how well medications like cyclosporine (an immunosuppressant) prevent the immune system from attacking the body's own cells after the transplant. Infants younger than 3 years diagnosed with certain aggressive blood cancers may be eligible to join. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people, offering a promising opportunity for eligible patients.

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 using umbilical cord blood for leukemia transplants is generally safe. Studies comparing transplants with one or two units of cord blood have found both methods potentially effective and safe. Early data on transplants using two units suggest safety and might even provide a higher dose of cells needed for the transplant.

Patients who received these transplants experienced different survival rates based on various factors, but overall, the treatments were well-tolerated. No clear evidence indicates that using two units improves survival over one, but both options consistently demonstrate safety.

While these treatments are in a phase II trial, earlier studies have already shown promise for safety. This suggests researchers are confident that the treatment is safe enough for further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using umbilical cord blood transplantation (UCBT) for infant leukemia because it offers a unique approach compared to traditional bone marrow transplants. Unlike the standard treatments, which usually rely on matched bone marrow donors, UCBT can be done with less stringent matching, making it more accessible for infants. Moreover, umbilical cord blood is rich in stem cells, which can help rebuild a healthy immune system more quickly and effectively. This could potentially lead to better outcomes and quicker recovery times for infants battling leukemia.

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

Research has shown that umbilical cord blood transplants can help treat acute leukemia in children. In this trial, participants will receive either a single or double unit umbilical cord blood transplant. Studies indicate that both single and double unit transplants can lead to high survival rates. Double unit transplants might offer better protection against leukemia recurrence. Specifically, one study found that children with acute leukemia had a 59% chance of remaining disease-free after receiving a cord blood transplant. Both single and double unit transplants have successfully cured many children with leukemia, even when the donor is not a perfect match. ^{1 2 3 6 7}

Who Is on the Research Team?

Christen Ebens, MD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Are You a Good Fit for This Trial?

This trial is for infants under 3 years old with high-risk acute leukemia or myelodysplastic syndromes. They must be in complete remission or early relapse, have a matched donor for stem cell transplant, and good organ function. Infants can't join if they have an active infection, HIV, extramedullary disease, or had a myeloablative transplant within the last 6 months.

Inclusion Criteria

My leukemia has high-risk features and is either in remission or early relapse.

My leukemia is high risk, in remission, and my bone marrow shows less than 5% blasts.

My liver tests are within 5 times the normal range.

Exclusion Criteria

I have a history of HIV or tested positive for it.

I do not have an active infection, including mold infections, at the time of transplantation.

I had a bone marrow transplant less than 6 months ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive a myeloablative conditioning regimen comprising busulfan, fludarabine, and melphalan to prepare for stem cell transplantation

2-3 weeks

Transplantation

Participants undergo umbilical cord blood transplantation (UCBT) with one or two units, depending on availability

1 day

1 visit (in-patient)

Post-Transplant Monitoring

Participants are monitored for engraftment and acute graft-versus-host disease (GVHD) up to day 100 post-transplant

100 days

Follow-up

Participants are monitored for chronic GVHD, survival, and developmental outcomes

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Busulfan
• Cyclosporine
• Fludarabine Phosphate
• Melphalan
• Umbilical Cord Blood Transplantation

Trial Overview The study tests how well chemotherapy (busulfan, fludarabine, melphalan) followed by umbilical cord blood stem cell transplant works in treating infant leukemia. It also looks at preventing immune reactions against normal cells using cyclosporine and mycophenolate mofetil after the transplant.

How Is the Trial Designed?

Group I: Single Unit UCB Transplantation Experimental Treatment 7 Interventions

Patients that receive one unit of umbilical cord blood transplantation (only if 2 adequate size and matched units are not available).

Group II: Double Unit UCB Transplantation Experimental Treatment 7 Interventions

Patients that receive 2 units of umbilical cord blood transplantation (UCBT).

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?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

Published Research Related to This Trial

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]

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 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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7101701/

Double umbilical cord blood transplantation for children ... The event-free survival (EFS) of leukemia and other hematologic disease were 59% and 53%, respectively, and the EFS of acute leukemia patients who received ...

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

Single vs double umbilical cord blood transplantation in ... The study concludes that both single and double UCBT are potentially effective treatments for acute leukemia, but the treatment choice should consider various ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00412360

NCT00412360 | Single vs Double Umbilical Cord Blood ... Pilot data suggest that infusion of two partially human leukocyte antigen (HLA)-matched UCB units, which always augments the graft cell dose, is safe and may ...

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

Single-Unit versus Double-Unit Umbilical Cord Blood ... Double UCBT may have a better graft-versus-leukemia effect in patients with MRD. ABSTRACT. We previously reported in a French prospective randomized study that ...

5. ashpublications.org ashpublications.org/blood/article/114/19/4293/26811/Relapse-risk-after-umbilical-cord-blood

enhanced graft-versus-leukemia effect in recipients of 2 units This analysis reveals an enhanced graft-versus-leukemia effect in acute leukemia patients after transplantation with 2 partially HLA-matched UCB units.

6. haematologica.org haematologica.org/article/view/6049

An overview of the progress on double umbilical cord ... We present here a brief overview of the clinical experience on double umbilical cord blood transplantation and its underlying biology.

7. ashpublications.org ashpublications.org/blood/article/120/21/359/86010/No-Survival-Advantage-After-Double-Umbilical-Cord

No Survival Advantage After Double Umbilical Cord Blood ... In children with hematological malignancies, outcomes were similar with no survival advantage in recipients of a double UCB transplant as ...