A Trial Comparing Unrelated Donor BMT With IST for Pediatric and Young Adult Patients With Severe Aplastic Anemia (TransIT, BMT CTN 2202) (TransIT)

K
Kathleen Overholt, MD

Primary Investigator

Enrolling By Invitation
25 years or below
All
Phase 3
234 participants needed
1 Location

Brief description of study

Severe Aplastic Anemia (SAA) is a rare condition in which the body stops producing enough new blood cells. SAA can be cured with immune suppressive therapy or a bone marrow transplant. Regular treatment for patients with aplastic anemia who have a matched sibling (brother or), or family donor is a bone marrow transplant. 
 
Patients without a matched family donor are treated with immune suppressive therapy (IST). Match unrelated donor (URD) bone marrow transplant (BMT) is used as a secondary treatment in patients who did not get better with IST, had their disease come back, or a new worse disease replaced it (like leukemia).
 
This study treatment does not include any investigational drugs. The medicines and procedures of this study are standard for treatment of SAA.

Detailed description of study

This study is a multi-center randomized phase III trial to compare the failure free survival between those randomized to IST vs 9-10/10 HLA matched URD BMT. The study will also address outcomes and gonadal function in each arm and explore critical biologicals including assessing germline genetic mutations associated with pediatric SAA that lead to a predisposition to the disease and the risk of development of clonal hematopoiesis following IST vs BMT in pediatric and young adult SAA.
 
Duration of subject participation for all study procedures in this study will be up to 2 years after treatment; a single later timepoint between 3 and 5 years will be collected to follow patients for specific protocol defined late effects and survival.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Severe Aplastic Anemia, Riley
  • Age: 25 years or below
  • Gender: All

Inclusion Criteria:

To be eligible to participate in the randomized trial, an individual must meet all the following criteria:

  1. Provision of signed and dated informed consent form for the randomized trial by patient and/or legal guardian.
  2. Age ≤25 years old at time of randomized trial consent.
  3. Confirmed diagnosis of idiopathic SAA, defined as:

    1. Bone marrow cellularity <25%, or <30% hematopoietic cells.
    2. Two of three of the following (in peripheral blood): neutrophils <0.5 x 10^9/L, platelets <20 x 10^9/L, absolute reticulocyte count <60 x 10^9/L or hemoglobin <8 g/dL.
  4. No suitable fully matched related donor available (minimum 6/6 match for HLA-A and B at intermediate or high resolution and DRB1 at high resolution using DNA based typing).
  5. At least 2 unrelated donors noted on NMDP search who are well matched (9/10 or 10/10 for HLA-A, B, C, DRB1, and DQB1 using high resolution).
  6. In the treating physician's opinion, no obvious contraindications precluding them from BMT or IST.

Exclusion Criteria:

  1. Presence of Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconi anemia must be excluded by diepoxybutane (DEB) or equivalent testing on peripheral blood or marrow. Telomere length testing should be sent on all patients to exclude Dyskeratosis Congenita (DC), but if results are delayed or unavailable and there are no clinical manifestations of DC, patients may enroll. If patients have clinical characteristics suspicious for Shwachman-Diamond syndrome, this disorder should be excluded by pancreatic isoamylase testing or gene mutation analysis (note: pancreatic isoamylase testing is not useful in children <3). Other testing per center may be performed to exclude IBMFS.
  2. Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) pattern consistent with pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination.
  3. Known severe allergy to ATG.
  4. Prior allogeneic or autologous stem cell transplant.
  5. Prior solid organ transplant.
  6. Infection with human immunodeficiency virus (HIV).
  7. Active Hepatitis B or C. This only needs to be excluded in patients where there is clinical suspicion of hepatitis (e.g., elevated LFTs).
  8. Female patients who are pregnant or breast-feeding.
  9. Prior malignancies except resected basal cell carcinoma or treated cervical carcinoma in situ.
  10. Disease modifying treatment prior to study enrollment, including but not limited to use of androgens, eltrombopag, romiplostim, or immune suppression. Note: Supportive care measures such as G-CSF, blood transfusion support and antibiotics are allowable

Updated on 27 May 2025. Study ID: PHO-PTCTC-TRANSIT, 16968, IRB-2020-0438
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Interested in the study?

This study is accepting only persons who receive care at a certain clinic or doctor or who are part of an invited group. Questions about this study can be directed to the study team listed in the description or contact your doctor to see if you are eligible.

Accepting referrals by invitation only