TransIT3: Study of Immune Therapy vs. Unrelated Donor Transplant for Severe Aplastic Anemia in Children

Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder characterized by pancytopenia with hypocellular marrow due to the attack of autoreactive T cells against hematopoietic stem and progenitor cells. Treatment options include immunosuppressive therapy (IST) or a bone marrow transplant (BMT). For patients with a matched sibling donor, BMT is the standard upfront treatment. Patients without a matched sibling typically receive first-line IST with horse antithymocyte globulin (hATG) and cyclosporine. 

BMT with an unrelated donor is a secondary treatment option for patients who are refractory to IST, who relapsed after IST, or who progressed to myelodysplastic syndrome (MDS). Some studies suggest comparable overall survival between upfront unrelated donor BMT and IST. However, the optimal upfront treatment approach remains unknown.

This prospective, randomized Phase 3 trial will compare MUD BMT to IST as the initial treatment for pediatric patients with SAA. Patients will be randomized 1:1 and will receive either matched, unrelated donor BMT or IST with hATG and cyclosporine. Participants will be followed for 5 years with clinical assessments, quality of life assessment, correlative studies on blood and bone marrow, and monitoring for treatment outcome. 

The study aims to determine the optimal first-line treatment for children with SAA in the absence of a matched sibling donor. Correlative studies will provide insights into disease biology and treatment effects. Results may help guide upfront treatment recommendations for this rare condition.

Primary Objectives

• Determine the optimal, upfront therapy for pediatric SAA in the absence of a matched sibling donor. 
• Compare time to treatment failure or death from any cause in both IST and unrelated donor BMT 
• Compare engraftment rates, acute and chronic graft-versus-host disease, immune reconstitution, quality of life, and risk of secondary MDS or acute myeloid leukemia 
• Gain a greater understanding of disease biology through collaborative research

Eligibility Criteria

Inclusion criteria include:

• Idiopathic SAA
• Up to 25 years old
• No fully matched sibling donor available
• Has at least 2 matched, unrelated donors

Exclusion criteria include: 

• Inherited bone marrow failure syndromes 
• Clonal cytogenetic abnormalities, pre-MDS, or MDS 
• Severe allergy to anti-thymocyte globulin 
• Prior allogeneic or autologous stem cell transplant or solid organ transplant
• Prior cancer
• Disease-modifying treatment 

Study Sites

St. Jude Children’s Research Hospital, Memphis, Tennessee
Collaborating sites in the U.S.

About this study

Severe aplastic anemia (SAA) is a rare disease where the body stops making enough new blood cells. The patient’s immune system attacks their bone marrow. This makes it difficult for the bone marrow to make healthy blood cells.

If the patient has a sibling (brother or sister), or other family member whose bone marrow fully matches, they are usually treated with a bone marrow transplant (BMT), which is also known as a hematopoietic cell transplant or HCT. This transplant helps the patient make new, healthy cells.

If no family member is a match, the patient may get a treatment known as immunosuppressive therapy (IST). IST consists of 2 drugs (horse antithymocyte globulin and cyclosporine) that slow the immune system's attack on the bone marrow. 

Another treatment approach is a BMT from a matched unrelated donor. This is typically used for patients who do not respond to IST or have disease relapse. But in recent years we have learned that BMT from matched unrelated donors given as upfront therapy offers excellent cure rates. 

This clinical trial studies SAA patients who have no matched sibling donors. Some patients will be chosen at random to receive IST as their first treatment. The other group will get a matched unrelated donor HCT as their first treatment. Our aim is to see how well these treatments work and which gives fewer side effects.

Scientists will follow study participants for 5 years from the time they start the trial. Patients will have medical visits, lab tests, and be asked about any side effects and their quality of life. 

Purpose of this clinical trial

• Find out whether IST or matched unrelated donor BMT leads to better survival and fewer problems 
• Help scientists better understand the disease

Eligibility overview

• Severe aplastic anemia
• Up to 25 years old
• Does not have a fully matched sibling donor
• Has at least 2 matched, unrelated donors