Bone Marrow Transplant for Aplastic Anemia

(BMT CTN CureAA Trial)

Recruiting at 21 trial locations

Overseen By Jennifer Romeril

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Must not be taking: Immunosuppressive therapy

Disqualifiers: Inherited bone marrow failure, MDS, 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: Unknown

60 Participants Needed

Trial Summary

What is the purpose of this trial?

BMT CTN 2207 will investigate the use of marrow transplantation for treatment of severe aplastic anemia that has not previously been treated.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you have been treated for severe aplastic anemia with certain therapies like immunosuppressive drugs, you may not be eligible to participate.

What data supports the effectiveness of the treatment Haploidentical donor bone marrow transplant for aplastic anemia?

Research shows that haploidentical bone marrow transplants for severe aplastic anemia have similar survival outcomes to transplants from matched sibling or unrelated donors, with a high rate of successful engraftment (when the new bone marrow starts to grow and make healthy blood cells). This treatment has improved over time, especially with techniques that reduce complications like graft-versus-host disease (when the new immune cells attack the patient's body). ^{1 2 3 4 5}

Is bone marrow transplant for aplastic anemia safe?

Bone marrow transplants for aplastic anemia have been studied and generally show that they can be safe, but there are risks like graft failure (when the new cells don't grow) and graft-versus-host disease (when the new cells attack the body). Safety has improved over the years, especially for younger patients, but some long-term side effects like cataracts and joint problems can occur. ^{2 6 7 8 9}

How is the bone marrow transplant treatment for aplastic anemia different from other treatments?

This treatment uses a haploidentical (partially matched) donor for bone marrow transplantation, which is an option for patients who do not have a fully matched sibling donor. It includes high-dose cyclophosphamide after the transplant to reduce the risk of graft-versus-host disease, making it a viable alternative for those with severe aplastic anemia who are refractory to other treatments. ^{2 5 10 11 12}

Eligibility Criteria

This trial is for individuals with severe aplastic anemia who haven't been treated before. It's open to those eligible for bone marrow transplants from half-matched (haploidentical) or completely unrelated donors.

Inclusion Criteria

Participant and/or legal guardian must sign informed consent

I can care for myself but may need occasional help.

I am between 3 and 75 years old.

Exclusion Criteria

I have tried treatments to reduce my body's reaction to a transplant.

I have had a stem cell transplant from a donor.

I have had a solid organ transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive a reduced-intensity preparative regimen of fludarabine, cyclophosphamide, low dose total body irradiation, and Thymoglobulin®

1-2 weeks

Transplantation

Bone marrow is collected from donors and transplanted into patients

1 day

Post-Transplant Follow-up

Participants are monitored for safety and effectiveness, including GVHD prophylaxis and hematologic response

1 year

Regular visits as per protocol

Treatment Details

Interventions

• Haploidentical donor bone marrow transplant
• Unrelated donor bone marrow transplant

Trial Overview The study compares two types of bone marrow transplants in treating severe aplastic anemia: one from a half-matched family member and another from a non-related donor.

Participant Groups

Group I: Unrelated donor transplantation Active Control 1 Intervention

Patients receiving bone marrow transplanted from an unrelated donor will be included in this arm.

Group II: Haploidentical transplantation Active Control 1 Intervention

Patients receiving bone marrow transplanted from a haploidentical related donor will be included in this arm.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Sanofi

Industry Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

A multicenter study involving 392 patients with severe aplastic anemia (SAA) found that haploidentical transplantation from various family members (fathers, mothers, siblings, and children) resulted in high engraftment rates (99.5%) and similar overall survival rates, indicating that all these donor types are effective options.

The study revealed that patients with a shorter history of SAA (less than 12 months) and better performance status had significantly better overall survival and failure-free survival, suggesting that these factors are important for optimizing transplant outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Who is the best haploidentical donor for acquired severe aplastic anemia? Experience from a multicenter study. Xu, LP., Wang, SQ., Ma, YR., et al.[2020]

HLA-haploidentical donor hematopoietic transplantation (Haplo-HSCT) for severe aplastic anemia (SAA) showed a high overall survival rate of 91.3% in a study of 50 patients, with no significant difference in outcomes compared to unrelated donor transplantation (UD-HSCT).

However, Haplo-HSCT was associated with a significantly higher incidence of acute and chronic graft-versus-host disease (aGVHD and cGVHD) and viral infections (CMV and EBV viremia) compared to UD-HSCT, indicating potential safety concerns despite its comparable efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[HLA- haploidentical donor hematopoietic transplantation for severe aplastic anemia achieved comparable outcomes with HLA- unrelated donor transplantation]. Lu, Y., Wu, T., Cao, X., et al.[2020]

In a study of 67 pediatric patients with severe aplastic anemia, haploidentical family donor transplants led to significantly faster neutrophil engraftment (10 days) compared to matched sibling (14 days) and unrelated donor transplants (12 days).

The 5-year overall survival rate was high at 93.8%, with no significant differences in survival outcomes based on donor type, indicating that haploidentical transplantation is a viable and effective option for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparable Outcome with a Faster Engraftment of Optimized Haploidentical Hematopoietic Stem Cell Transplantation Compared with Transplantations from Other Donor Types in Pediatric Acquired Aplastic Anemia. Kim, H., Im, HJ., Koh, KN., et al.[2020]

Hematopoietic stem cell transplantation (BMT) is the only curative treatment for severe aplastic anemia, with HLA-matched sibling donor transplants being the standard care for younger patients.

The use of high-dose post-transplant cyclophosphamide has significantly improved outcomes in haploidentical BMT by reducing the risks of graft rejection and graft-versus-host disease, making it a viable option for patients with refractory or relapsed disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical Donor Bone Marrow Transplantation for Severe Aplastic Anemia. DeZern, AE., Brodsky, RA.[2023]

Haploidentical allogeneic hemopoietic stem cell transplantation (allo-HSCT) was found to be safe and effective for treating severe aplastic anemia (SAA) in 8 patients, with successful hematopoietic reconstitution achieved in all cases within an average of 14.8 days for neutrophils and 15.0 days for platelets.

While complications such as acute graft versus host disease (aGVHD) occurred in 7 patients, no severe complications like veno-occlusive disease or hemorrhagic cystitis were reported, and there were no transplantation-related deaths during a median follow-up of 8.5 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications of haploidentical hematopoietic stem cell transplantation in severe aplastic anemia. Zhang, P., Feng, K., Xue, Y., et al.[2018]

Haploidentical stem cell transplantation (HSCT) is a feasible and effective upfront treatment for severe aplastic anemia (SAA) patients, showing similar overall and failure-free survival rates compared to matched related donor transplants, with 86.1% and 91.3% survival rates respectively over three years.

While haploidentical HSCT was associated with a higher incidence of acute and chronic graft-versus-host disease (GVHD), the overall safety profile remains acceptable, indicating that this method can be a viable alternative for patients without suitable donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant. Xu, LP., Jin, S., Wang, SQ., et al.[2022]

Bone marrow transplantation is a key treatment for severe aplastic anemia and acute leukemia, requiring an HLA-matched sibling donor, but does not require ABO blood type compatibility.

Survival rates after transplantation are 17% for acute leukemia and 40% for aplastic anemia, with significant complications including immune rejection and graft versus host disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Allogenic bone marrow grafts (author's transl)]. Gluckman, E., Marty, M., Boiron, M.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Who is the best haploidentical donor for acquired severe aplastic anemia? Experience from a multicenter study. [2020]

2. China pubmed.ncbi.nlm.nih.gov

[HLA- haploidentical donor hematopoietic transplantation for severe aplastic anemia achieved comparable outcomes with HLA- unrelated donor transplantation]. [2020]

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

Comparable Outcome with a Faster Engraftment of Optimized Haploidentical Hematopoietic Stem Cell Transplantation Compared with Transplantations from Other Donor Types in Pediatric Acquired Aplastic Anemia. [2020]

4. Japan pubmed.ncbi.nlm.nih.gov

Stem cell transplantation for aplastic anemia. [2019]

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

Haploidentical Donor Bone Marrow Transplantation for Severe Aplastic Anemia. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Clinical applications of haploidentical hematopoietic stem cell transplantation in severe aplastic anemia. [2018]

7. China pubmed.ncbi.nlm.nih.gov

[Clinical analysis of haploidentical or unrelated donor hematopoietic stem cell transplantation for patients with severe aplastic anemia]. [2016]

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

Current status of allogeneic bone marrow transplantation in acquired aplastic anemia. [2021]

9. Germany pubmed.ncbi.nlm.nih.gov

Donor-derived marrow mesenchymal stromal cell co-transplantation following a haploidentical hematopoietic stem cell transplantation trail to treat severe aplastic anemia in children. [2019]

10. Italy pubmed.ncbi.nlm.nih.gov

[Bone marrow transplantation in the treatment of severe aplastic anemia]. [2006]

11. England pubmed.ncbi.nlm.nih.gov

Upfront haploidentical transplant for acquired severe aplastic anemia: registry-based comparison with matched related transplant. [2022]

12. France pubmed.ncbi.nlm.nih.gov

[Allogenic bone marrow grafts (author's transl)]. [2021]