Haploidentical Transplant for Severe Aplastic Anemia

Overseen By Amr Qudeimat, MD

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Alemtuzumab, ATG

Disqualifiers: Fanconi anemia, Dyskeratosis congenita, 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

21 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for treating Severe Aplastic Anemia (SAA) using a type of stem cell transplant from a partially matched family member, known as Haploidentical Hematopoietic Cell Transplantation (Haploidentical HCT). The goal is to determine if this approach can help patients recover blood cell production and improve survival without serious side effects. The trial seeks participants with severe aplastic anemia who have tried other treatments without success and lack a fully matched donor. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the trial involves a complex medical procedure like a haploidentical transplant, it's important to discuss your current medications with the trial team to ensure safety and compatibility.

What prior data suggests that this haploidentical transplantation method is safe for patients with severe aplastic anemia?

Research has shown that haploidentical hematopoietic stem cell transplantation (Haplo-HCT) has been studied in patients with severe aplastic anemia. This transplant uses a family donor who is a partial match instead of a full match. Studies have found that patients receiving this treatment often experience outcomes similar to those with fully matched donor transplants, suggesting it could be a safe option when a fully matched donor isn't available.

The treatment is generally well-tolerated. Patients have demonstrated good rates of engraftment, meaning the new cells start to grow and produce healthy blood cells. However, like any medical treatment, side effects can occur. Some studies report a risk of developing graft-versus-host disease (GVHD), where the donor's cells attack the patient's body, but this is often manageable with medication.

Overall, existing research provides promising evidence about the safety of haplo-HCT for severe aplastic anemia, with outcomes supporting its use when fully matched donors are not an option. However, discussing potential risks and benefits with healthcare providers before joining a trial is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about haploidentical hematopoietic cell transplantation (HCT) for severe aplastic anemia because it offers a novel approach for patients who don't have an HLA-matched donor. Unlike traditional treatments that often require perfectly matched donors, this method uses haploidentical, or half-matched, donors, making transplants more accessible. The treatment also aims to minimize post-transplant complications by eliminating the need for post-transplant pharmacologic immunosuppression, which is typically necessary to prevent graft-versus-host disease (GVHD). This could reduce toxicity and enhance recovery, providing a promising alternative to conventional therapies.

What evidence suggests that haploidentical HCT could be an effective treatment for severe aplastic anemia?

Research has shown that haploidentical hematopoietic cell transplantation (HCT), which participants in this trial will receive, can benefit patients with severe aplastic anemia lacking a perfectly matched donor. Studies have found that this treatment can achieve survival rates similar to those of transplants from fully matched donors. Specifically, patients have experienced better long-term outcomes with this method. The treatment is considered safe and effective, even when other options are unavailable, making it a promising choice for those needing a transplant without a perfect donor match. ^{1 2 6 7 8}

Who Is on the Research Team?

Amr Qudeimat, MD

Principal Investigator

St. Jude Children's Research Hospital

Akshay Sharma, MBBS

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for patients under 21 with Severe Aplastic Anemia who have failed at least one immunosuppressive therapy, lack a fully matched donor, and have good organ function. Donors must be family members partially matching the patient (≥3 of 6 HLA types), willing to donate stem cells, and HIV negative. Pregnant or breastfeeding women can't participate.

Inclusion Criteria

I don't have a matching family or unrelated donor for a cell transplant.

My potential donor is ready and can donate stem cells.

You are not currently breastfeeding a baby.

Exclusion Criteria

You had a life-threatening reaction (like anaphylaxis) to ATG in the past, which means you cannot use it again.

I do not have an ongoing infection that isn't getting better with treatment.

I have been diagnosed with dyskeratosis congenita.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Participants receive chemotherapy, antibodies, and radiation to prepare the body for donor cell infusion

2-3 weeks

Transplantation

Participants receive a progenitor blood cell infusion followed by a donor lymphocyte infusion

1 week

Engraftment

Monitoring of engraftment and initial immune reconstitution

4 weeks

Follow-up

Participants are monitored for safety, effectiveness, and immune reconstitution post-transplant

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Haploidentical HCT

Trial Overview The study tests haploidentical hematopoietic cell transplantation (HCT) in SAA patients using chemotherapy, radiation, transplanted cells from half-matched family donors, and additional white blood cell infusions. It aims to assess engraftment success at 30 days post-transplantation and survival rates after one year.

How Is the Trial Designed?

Group I: Haploidentical HCT Experimental Treatment 9 Interventions

To assess the safety and efficacy of haploidentical donor transplantation for patients with severe aplastic anemia who lack an available HLA-matched donor. The goal of this study is to develop a novel, reduced-toxicity, post-transplant pharmacologic immunosuppression (GVHD prophylaxis)- free, highly tolerogenic haploidentical transplant regimen that is associated with few post- transplant complications or late toxicities and is available promptly to all patients, irrespective of matched donor availability. Cells for infusion are prepared using the CliniMACS System.

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

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 189 patients with severe aplastic anemia (SAA) who underwent either HLA-haploidentical or HLA-identical hematopoietic stem cell transplantation (HSCT), the 5-year overall survival rate was 72.0% for the HLA-haploidentical group, which is slightly lower than the 76.5% for the HLA-identical group.

The study suggests that HLA-haploidentical HSCT is a viable option for SAA patients under 40 years old who do not have a matched sibling donor, as older patients showed poorer outcomes in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal donor for severe aplastic anemia patient requiring allogeneic hematopoietic stem cell transplantation: A large-sample study from China. Zeng, Y., Wang, S., Wang, J., et al.[2018]

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]

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) showed a survival rate of 71.4% in 21 patients with severe aplastic anemia (SAA) over a follow-up period of 16 months, indicating its therapeutic efficacy.

While the treatment was effective, 66.7% of patients experienced graft versus host disease (GVHD), with some cases being severe, highlighting the need for careful monitoring and management of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Retrospective analysis of therapeutic efficacy of haploidentical allogeneic hematopoietic stem cell transplantation for severe aplastic anemia]. Zhang, Y., Liu, XD., He, XP., et al.[2018]

In a study of 26 adult patients with severe aplastic anemia (SAA) who underwent HLA-haploidentical hematopoietic stem cell transplantation (HSCT), the engraftment rate was high at 92.3%, with most patients achieving engraftment within 13 days after the procedure.

The overall survival rate was 84.6% over an average follow-up of about 1313 days, indicating that HLA-haploidentical HSCT is a promising treatment option for adults with SAA when a fully matched donor is not available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcome of HLA-haploidentical hematopoietic SCT without in vitro T-cell depletion for adult severe aplastic anemia after modified conditioning and supportive therapy. Gao, L., Li, Y., Zhang, Y., et al.[2022]

Haploidentical stem cell transplantation (haplo-HSCT) has emerged as a promising treatment for severe aplastic anemia (SAA), providing a viable option when matched donors are not available, with improved survival outcomes due to advancements in treatment regimens.

The most successful regimen involves granulocyte colony-stimulating factor (G-CSF) combined with antithymocyte globulin (ATG), which has been widely adopted in China, while other regimens like posttransplantation cyclophosphamide (PT-Cy) and T-cell depletion (TCD) are also effective but have smaller sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical stem cell transplantation for aplastic anemia: the current advances and future challenges. Xu, ZL., Huang, XJ.[2021]

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 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]

In a study of 216 severe aplastic anemia patients undergoing haploidentical transplantation, 5.6% experienced severe cardiac toxicity, which significantly worsened their overall survival rates (12.5% vs. 89.6% for those without toxicity).

Four key predictors of severe cardiotoxicity were identified: a pre-transplant ECOG score of 2 or higher, abnormal ST-T waves on ECG, hyperlipaemia, and a high dose of cyclophosphamide (≥1.8 g/m2/d), indicating that patients with more risk factors had much poorer outcomes and should be monitored closely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and predictors of severe cardiotoxicity in patients with severe aplastic anaemia after haploidentical haematopoietic stem cell transplantation. Xu, ZL., Xu, LP., Zhang, YY., 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]

Citations

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

Outcomes of Haploidentical Stem Cell Transplantation in ... Our results suggest that Haplo-SCT can be an effective option in both upfront and salvage settings when fully matched donors are not available.

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

Comparable Outcomes in Acquired Severe Aplastic ... We suggest that HID-HSCT might be a safety and effective option for SAA patients without a matched donor.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0304383525001582

Comparable survival outcomes in HLA-Matched and ... Our study includes 278 patients aged between 40 and 50 years from 29 centers who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) from ...

4. hematologyadvisor.com hematologyadvisor.com/news/aplastic-anemia-hct-ci-predicts-outcomes-hsct-stem-cell-treatment-risk/

HCT-CI Predicts Outcomes After Haplo-HSCT for Severe ... Researchers determined the HCT-CI was able to predict clinical outcomes among patients with severe aplastic anemia who underwent haplo-HSCT.

5. 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 Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option with significantly improved outcomes over the long term, ...

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

Outcomes of haploidentical stem cell transplantation in ... Our results suggest that Haplo-SCT can be an effective option in both upfront and salvage settings when fully matched donors are not available.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04558736

Haploidentical HCT for Severe Aplastic Anemia The primary objective is to assess the rate of engraftment at 30 days and overall survival (OS) and event free survival (EFS) at 1 year post-hematopoietic cell ...

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

The outcomes of second haploidentical donor ... This study aimed to evaluate the outcomes of second haploidentical hematopoietic stem cell transplantation (HID-HSCT) for patients with severe aplastic anaemia ...