Hematopoietic Cell Transplant for Aplastic Anemia

Overseen By Christen Ebens, MD, MPH

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Masonic Cancer Center, University of Minnesota

Disqualifiers: Pregnancy, Uncontrolled infection, Advanced 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

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 tests a new approach for treating certain blood disorders using a hematopoietic cell transplant, which replaces damaged blood-forming cells with healthy ones. It targets conditions like severe aplastic anemia and paroxysmal nocturnal hemoglobinuria, using a gentler transplant preparation followed by a specific drug to aid in accepting new cells. The trial includes two groups: one for individuals with clonal hematopoiesis (abnormal blood cell growth) and one for those without it. Ideal participants have severe blood disorders that have not responded to treatment or have experienced transplant failure. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group of people.

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 study team or your doctor.

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

Research has shown that blood stem cell transplants, especially with a gentler preparation process, offer promising treatment for severe aplastic anemia and similar conditions. These transplants replace unhealthy blood-forming cells with healthy ones from a donor. Studies have demonstrated that this procedure can be quite effective for certain patients.

Regarding safety, the transplant method used in this trial, along with cyclophosphamide to help prevent complications, remains under study. Previous patients have generally tolerated the treatment well, but information on its long-term safety is limited. Common risks include infections and the possibility of graft-versus-host disease, where donor cells attack the body. Medications and careful monitoring usually manage these risks.

Overall, while this treatment has potential, participants should be aware of the possible risks and discuss them thoroughly with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about using Hematopoietic Cell Transplant (HCT) with Reduced Intensity Conditioning (RIC) and post-transplant Cyclophosphamide for treating aplastic anemia because it offers a potentially safer and more effective alternative to traditional high-dose conditioning regimens. Unlike standard treatments that often involve aggressive chemotherapy, this approach uses reduced intensity conditioning, which might lessen side effects and make the treatment more accessible to older and more vulnerable patients. Additionally, the use of Cyclophosphamide after the transplant helps prevent graft-versus-host disease (GvHD), a common complication, by selectively targeting immune cells that may attack the donor stem cells. This combination could enhance patient recovery and improve overall outcomes, making it a promising option for those battling aplastic anemia.

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

Research has shown that hematopoietic stem cell transplantation (HSCT) can effectively treat severe aplastic anemia (SAA), with studies indicating a success rate of nearly 90%. In this trial, participants will receive HSCT with a gentler treatment approach known as reduced intensity conditioning (RIC), which is easier on the body. The trial also includes post-transplant cyclophosphamide (PTCy) to help prevent complications like graft-versus-host disease (GvHD) and improve outcomes. This method has succeeded even with donors who are not fully matched or are unrelated. Overall, this approach offers promising results for people with conditions like SAA, paroxysmal nocturnal hemoglobinuria (PNH), and similar disorders. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people with severe bone marrow failure conditions like aplastic anemia or paroxysmal nocturnal hemoglobinuria. Participants must have specific blood and bone marrow characteristics, such as low reticulocyte count or evidence of one to three-lineage aplasia, and adequate organ function. Those who've had a previous transplant that didn't work may also qualify.

Inclusion Criteria

My bone marrow has less than 5% blasts and I've never had MDS/AML.

My bone marrow has less than 5% blasts and I've never had MDS/AML.

My platelet count is below 20,000/uL or I need regular transfusions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning and Transplantation

Participants undergo reduced intensity conditioning followed by hematopoietic cell transplant and post-transplant cyclophosphamide

Up to 180 days

Multiple visits for conditioning and transplantation procedures

GvHD Prophylaxis

Participants receive GvHD prophylaxis through day +180 post-transplant

180 days

Follow-up

Participants are monitored for safety and effectiveness, including incidence of GvHD and survival outcomes

2 years

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Hematopoietic Cell Transplant With Reduced Intensity Conditioning and Post-transplant Cyclophosphamide

Trial Overview The study tests a less intense cell transplant method combined with post-transplant cyclophosphamide medication in patients with certain bone marrow failures. It includes individualized dosing based on pharmacokinetics and varying radiation doses by age and disease features.

How Is the Trial Designed?

Group I: Arm B: Clonal hematopoiesis Experimental Treatment 9 Interventions

Participants 25-75 years old and/or with clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.

Group II: Arm A: No clonal hematopoiesis Experimental Treatment 9 Interventions

Participants 25 years of age and younger with no clonal hematopoiesis. Active study treatment includes the conditioning regimen followed by the stem cell infusion and GvHD prophylaxis through day +180. Supportive care and follow up activities continue through two years post HCT.

Hematopoietic Cell Transplant With Reduced Intensity Conditioning and Post-transplant Cyclophosphamide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Allogeneic Hematopoietic Cell Transplantation for:

• Severe aplastic anemia
• Paroxysmal nocturnal hemoglobinuria
• Acquired pure red cell aplasia
• Acquired amegakaryocytic thrombocytopenia
• Diamond-Blackfan anemia
• Fanconi's anemia

Approved in United States as Allogeneic Hematopoietic Cell Transplantation for:

• Severe aplastic anemia
• Paroxysmal nocturnal hemoglobinuria
• Acquired pure red cell aplasia
• Acquired amegakaryocytic thrombocytopenia
• Diamond-Blackfan anemia
• Fanconi's anemia

Approved in Canada as Allogeneic Hematopoietic Cell Transplantation for:

• Severe aplastic anemia
• Paroxysmal nocturnal hemoglobinuria
• Acquired pure red cell aplasia
• Acquired amegakaryocytic thrombocytopenia
• Diamond-Blackfan anemia
• Fanconi's anemia

Approved in Japan as Allogeneic Hematopoietic Cell Transplantation for:

• Severe aplastic anemia
• Paroxysmal nocturnal hemoglobinuria
• Acquired pure red cell aplasia
• Acquired amegakaryocytic thrombocytopenia
• Diamond-Blackfan anemia
• Fanconi's anemia

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

In a study of 16 patients with refractory severe aplastic anemia, haploidentical stem cell transplantation (HSCT) using reduced-intensity conditioning and post-transplant cyclophosphamide resulted in a high neutrophil engraftment rate of 94% and a platelet engraftment rate of 75%.

The approach demonstrated a 1-year overall survival rate of 67.1% and a low incidence of acute graft-versus-host disease (GVHD), suggesting it is a promising therapeutic option for patients lacking matched donors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haploidentical BMT and post-transplant Cy for severe aplastic anemia: a multicenter retrospective study. Esteves, I., Bonfim, C., Pasquini, R., et al.[2018]

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is recommended as the first-line treatment for patients under 40 with stage 3-5 aplastic anemia who have HLA-matched sibling donors, but alternative donor options should be considered for those not responding to immunosuppressive therapy.

The use of a reduced dose of cyclophosphamide combined with fludarabine is becoming the preferred conditioning regimen to minimize cardiotoxicity, while HLA-haploidentical SCT from related donors is gaining attention for its low transplant-related mortality and reduced risk of chronic graft-versus-host disease (GVHD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hematopoietic stem cell transplantation for acquired aplastic anemia]. Yamazaki, H.[2015]

In a study of 23 patients with severe aplastic anemia, a conditioning regimen of cyclophosphamide and low-dose total body irradiation resulted in only one case of graft rejection, suggesting this approach significantly reduces the risk of rejection compared to traditional methods.

The regimen did not increase the incidence of graft-versus-host disease or interstitial pneumonitis, and the survival rates were 61% at one year and 49% at 2.5 years, indicating it is a safe and effective treatment option for patients lacking predictive tests for graft rejection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevention of graft rejection following bone marrow transplantation. Gale, RP., Ho, W., Feig, S., et al.[2021]

Hematopoietic stem-cell transplantation (BMT) is the preferred treatment for young patients with acquired aplastic anemia who have a matched sibling donor, while immunosuppressive therapies are effective alternatives for older patients or those without suitable donors.

Current advancements in BMT from unrelated and mismatched donors are promising, but this option is mainly for patients who do not respond to or relapse after immunosuppressive therapy, highlighting the need for improved treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical management of aplastic anemia. Dezern, AE., Brodsky, RA.[2022]

In a study of 43 Fanconi anemia patients undergoing marrow transplantation with a reduced cyclophosphamide (CY) conditioning regimen (15 mg/kg/day for 4 days), 93% of patients are alive after a median follow-up of 3.7 years, indicating high efficacy and safety of this approach.

The study shows that using lower doses of CY results in low incidences of acute and chronic graft-versus-host disease (17% and 28.5%, respectively), confirming that this conditioning method minimizes toxicities while achieving successful engraftment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HLA-matched related donor hematopoietic cell transplantation in 43 patients with Fanconi anemia conditioned with 60 mg/kg of cyclophosphamide. Bonfim, CM., de Medeiros, CR., Bitencourt, MA., et al.[2021]

Early intervention with bone marrow transplantation can cure up to 80% of patients with severe aplastic anemia, highlighting the importance of timely treatment.

Intensive immunosuppression can also effectively rescue many patients, but both treatment options must be initiated before complications like infection and bleeding arise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Severe aplastic anemia]. Hinterberger, W.[2021]

In a study involving 65 patients with severe aplastic anemia, a new conditioning regimen using Cyclophosphamide and total body irradiation significantly reduced the risk of bone marrow graft rejection compared to previous regimens.

Despite challenges like graft versus host disease and infections, 50% of the patients achieved long-term survival and appeared cured of their disease, highlighting the efficacy of the new treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation in 65 patients with severe aplastic anemia. Gluckman, E., Devergie, A., Gerotta, I., et al.[2013]

In a study of 203 patients with aplastic anemia undergoing allogeneic stem cell transplantation, a low-dose cyclophosphamide (less than 100 mg/kg) regimen showed a trend towards higher five-year overall survival (93.0%) compared to high-dose (84.2%) and reduced-dose (83.8%) regimens.

The findings suggest that reducing the dose of cyclophosphamide does not compromise engraftment success and may improve survival outcomes, indicating a safer approach when combined with fludarabine in HLA-identical sibling transplants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of cyclophosphamide dose of conditioning on the outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia from human leukocyte antigen-identical sibling. Mori, T., Koh, H., Onishi, Y., et al.[2022]

A reduced-intensity conditioning regimen for severe aplastic anemia patients resulted in a promising 2-year survival rate of 73%, particularly among younger patients (84% survival for those 14 years or younger).

However, there was a notable 18% graft failure rate, especially in patients aged 15 and older, suggesting that the conditioning regimen may need adjustments for older adults to improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party. Bacigalupo, A., Locatelli, F., Lanino, E., et al.[2013]

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]

In a study of 17 patients with severe aplastic anemia who received bone marrow transplants (BMT) after a conditioning regimen of cyclophosphamide and total lymphoid irradiation, the long-term survival rate was 76% with a median follow-up of 11 years.

The conditioning regimen led to sustained engraftment in all patients, with manageable rates of graft-versus-host disease (24% for acute and 35% for chronic), and no patients developed malignancies post-transplant, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bone marrow transplantation for transfused patients with severe aplastic anemia using cyclophosphamide and total lymphoid irradiation as conditioning therapy: long-term follow-up from a single center. Gaziev, D., Giardini, C., Galimberti, M., et al.[2013]

Citations

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Allogeneic Hematopoietic Stem Cell Transplantation in ... Hematopoietic stem cell transplantation (HSCT) provides curative therapy in almost 90% of patients with severe aplastic anemia (SAA).

2. astctjournal.org astctjournal.org/article/S2666-6367(24)00682-1/fulltext

Evidence-Based Guidelines From the American Society for ... Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for severe aplastic anemia (SAA).

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2110/529736/Successful-Allogenic-Stem-Cell-Transplantation

Successful Allogenic Stem Cell Transplantation Using ... Recently, unrelated donor (URD) and haploidentical (HI) transplants have gained favor due to better outcomes with reduced intensity regimens ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2666636725014496

Excellent Outcomes in Feasibility Study of Radiation-free ... Radiation-free low-intensity conditioning was successful in pediatric aplastic anemia · Sustained donor cell engraftment with low graft-versus- ...

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1378432/full

The state of the art in the treatment of severe aplastic anemia In this paper, we present the state of the art in the management of severe AA for pediatric and adult patients based on the available guidelines and recently ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39307421/

Allogeneic Hematopoietic Cell Transplantation for the ... Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative treatment for severe aplastic anemia (SAA).

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/595/531265/Role-of-Age-and-Donor-Type-in-3646-Severe-Aplastic

Role of Age and Donor Type in 3646 Severe Aplastic Anemia ... Allogeneic hematopoietic stem cell transplantation (HSCT) is a standard treatment option for patients with acquired aplastic anemia (AA).

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666636725014472

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell ... While these therapies show great potential, they remain largely experimental, with limited long-term data on their safety, efficacy, and ...

9. aetna.com aetna.com/cpb/medical/data/600_699/0627.html

Hematopoietic Cell Transplantation for Aplastic Anemia ... This Clinical Policy Bulletin addresses hematopoietic cell transplantation for aplastic anemia and other bone marrow failure syndromes.