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

33 Participants Needed

Trial Summary

What is the purpose of this trial?

RATIONALE: Giving chemotherapy, such as busulfan, fludarabine, and melphalan, before a donor umbilical cord blood stem cell transplant helps stop the growth of abnormal or cancer cells and prepares the patient's bone marrow for the stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil may stop this from happening. PURPOSE: This phase II trial is studying how well combination chemotherapy followed by a donor umbilical cord blood transplant works in treating infants with high-risk acute leukemia or myelodysplastic syndromes.

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 for infant leukemia?

Research shows that a combination of busulfan, fludarabine, and melphalan is effective in treating high-risk myeloid malignancies in children, with patients remaining in remission and without severe side effects. This suggests potential effectiveness for infant leukemia as well. ^{1 2 3 4 5}

Is stem cell transplant using busulfan, fludarabine, and melphalan safe for infants with leukemia?

Research shows that using busulfan, fludarabine, and melphalan in stem cell transplants has an acceptable safety profile in children and young adults with high-risk conditions. While some side effects like gastrointestinal issues and rare serious complications can occur, the treatment is generally well-tolerated with careful monitoring. ^{1 2 4 6 7}

How is the treatment for infant leukemia using stem cell transplant with busulfan, fludarabine, and melphalan different from other treatments?

This treatment is unique because it combines busulfan, fludarabine, and melphalan as a conditioning regimen before umbilical cord blood transplantation, which is well-tolerated and effective in achieving remission without severe complications like graft-versus-host disease. It offers a promising alternative for high-risk infant leukemia, especially when conventional chemotherapy is not effective. ^{1 2 5 8 9}

Research Team

Christen Ebens, MD

Principal Investigator

Masonic Cancer Center, University of Minnesota

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. 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]

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

Allogeneic bone marrow transplantation for children with acute lymphoblastic leukemia conditioned with busulfan, cyclophosphamide and melphalan. [2013]

4. 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]

5. Denmark pubmed.ncbi.nlm.nih.gov

A conditioning regimen of busulfan, fludarabine, and melphalan for allogeneic stem cell transplantation in children with juvenile myelomonocytic leukemia. [2013]

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

Association between busulfan exposure and outcome in children receiving intravenous busulfan before hematologic stem cell transplantation. [2013]

8. England pubmed.ncbi.nlm.nih.gov

Treatment of infant leukemia with busulfan, cyclophosphamide +/- etoposide and bone marrow transplantation. [2013]

9. England pubmed.ncbi.nlm.nih.gov

Allogeneic bone marrow transplantation for childhood leukemia following a busulfan and melphalan preparative regimen. [2013]