Bone Marrow Transplant for Aplastic Anemia

(BMT CTN CureAA Trial)

Recruiting at 25 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores bone marrow transplants as a treatment for severe aplastic anemia, a condition where the bone marrow fails to produce enough blood cells, in patients who have not received prior treatment. It compares two types of transplants: one from an unrelated donor and another from a partially matched family member (haploidentical donor). Individuals diagnosed with severe aplastic anemia who have not yet received treatment may be suitable candidates for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both haploidentical and unrelated donor bone marrow transplants are promisingly safe for treating severe aplastic anemia.

For haploidentical transplants, one study found that about 94% of patients lived for at least four years after treatment. However, some patients experienced mild chronic graft-versus-host disease (GVHD), where the donated cells attack the body. Another study indicated a survival rate of about 65%, showing that results can vary.

Unrelated donor transplants also demonstrate strong survival rates. One study reported that 85% of patients survived for eight years, while another showed a 100% survival rate, with only mild cases of chronic GVHD. This suggests that most patients handled the treatment well.

While these findings are encouraging, individual experiences may differ. Discuss potential risks and benefits with healthcare providers before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these bone marrow transplants for aplastic anemia because they offer more donor options and potentially improve outcomes. Unlike traditional transplants that require a fully matched sibling donor, haploidentical transplants allow for donations from partially matched family members, making it easier to find a suitable donor. Meanwhile, unrelated donor transplants increase the donor pool by including non-family members. This flexibility can help patients receive transplants more quickly, which is crucial for treating this serious condition.

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

Research has shown that bone marrow transplants from a partially matched family donor (haploidentical donor), one of the treatment options in this trial, yield promising results for severe aplastic anemia. Studies found that about 94% of patients survived at least four years after this type of transplant, a notably high rate. Another option in this trial is bone marrow transplants from unrelated donors, with survival rates varying from 28% to 94% over five years. Some recent studies suggest that transplants from unrelated donors can achieve success similar to those from fully matched donors. Both types of transplants offer hope for people with severe aplastic anemia. ^{2 3 6 7 8}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

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astctjournal.org

astctjournal.org/article/S2666-6367(25)01363-6/abstract

Outcomes of Haploidentical Stem Cell Transplantation in ...

During a median follow-up of 54 mo, the 4-yr overall survival (OS) and failure-free survival were 93.9% and 92.4%, respectively. Four-year OS ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9713560/

Comparable long-term outcomes between upfront ...

Transplantation from identical sibling donors (ISD) has produced a long-term survival of approximately 90% and has been recommended as a first-line choice among ...

3.

sciencedirect.com

sciencedirect.com/science/article/abs/pii/S2666636725013636

Outcomes of haploidentical stem cell transplantation in ...

Four-year OS after upfront and salvage Haplo-SCT was 93.8% and 94.2%, respectively (P = 0.874). Four-year GFFS was 78.9%, and it did not differ ...

4.

ashpublications.org

ashpublications.org/bloodadvances/article/9/17/4448/537898/Up-front-alternative-donor-HCT-in-severe-aplastic

Up-front alternative donor HCT in severe aplastic anemia

Several studies in the contemporary era using alternative donor HCT for SAA show promising overall and failure-free survival rates, but less- ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9444987/

Haploidentical bone marrow transplantation in patients ...

Allogeneic bone marrow transplantation produces long-term survival approaching 90% at 5 years in patients younger than 20 years, and more than 75% for patients ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8820587/

Comparable Outcomes in Acquired Severe Aplastic ...

The OS rate for the patients of SAA received allo-HSCT has been above 70% (6), but only 50% in patients whose age over 40 years (18). Zeng et al. (16) ...

7.

astctjournal.org

astctjournal.org/article/S1083-8791(13)00059-1/fulltext

Excellent Outcome of Haploidentical Hematopoietic Stem ...

The overall survival rate was 64.5%. By contrast, in the present study, HHCT was successful in 12 children and adolescents with acquired SAA, none of whom had a ...

8.

link.springer.com

link.springer.com/article/10.1007/s00277-025-06440-9

The outcomes of second haploidentical donor ...

The 5-year overall survival (OS) rate was 47.1% ± 11.0%, with a median follow-up of 2037.5 days (range, 863–3488 days) among survivors.