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
Overview
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 donory are treated with immune suppressive therapy (IST). Match unrelated donor (URD) bonew 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 trial will compare time from randomization to failure of treatment or death from anyuse of IST versus URD BMT when used as initial therapy to treat SAA.
The trial will also assess whether health-related quality of life and early markers ofy differ between those randomized to URD BMT or IST, as well as assess the presencew failure-related genes and presence of gene mutations associated with MDS orukemia and the change in gene signatures after treatment in both study arms.
This study treatment does not include any investigational drugs. The medicines and procedureshis study are standard for treatment of SAA.
Description
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 addressd outcomes and gonadal function in each arm and explore critical biologicaluding assessing germline genetic mutations associated with pediatric SAA thaty 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.
This clinical trial will randomize 234 children/AYA over 3.3-4.7 years at a 1:1 ratio betweenwith immune suppression therapy (IST) with horse ATG (hATG)/cyclosporine
(CsA) versus well- matched (9-10/10 allele) unrelated donor (URD) bone marrow transplantation
(BMT) using a regimen of rabbit ATG (rATG)/fludarabine/cyclophosphamide and 200 cGy TBI.
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 tow patients for specific protocol defined late effects and survival.
Eligibility
You may be eligible for this study if you meet the following criteria:
-
Conditions:
Severe Aplastic Anemia
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Age: - 25 Years
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Gender: All
Inclusion Criteria:
To be eligible to participate in the randomized trial, an individual must meet all thewing criteria:1. Provision of signed and dated informed consent form for the randomized trial byd/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,<20 x 10^9/L, absolute reticulocyte count <60 x 10^9/L or hemoglobin <8g/dL.. No suitable fully matched related donor available (minimum 6/6 match for HLA-A and Bdiate or high resolution and DRB1 at high resolution using DNA basedyping).5. At least 2 unrelated donors noted on NMDP search who are well matched (9/10 or 10/10HLA-A, B, C, DRB1, and DQB1 using high resolution).6. In the treating physician's opinion, no obvious contraindications precluding them fromBMT or IST.usion Criteria:1. Presence of Inherited bone marrow failure syndromes (IBMFS). The diagnosis of Fanconiust be excluded by diepoxybutane (DEB) or equivalent testing on peripheralblood or marrow. Telomere length testing should be sent on all patients to excludeDyskeratosis Congenita (DC), but if results are delayed or unavailable and there areDC, patients may enroll. If patients have clinicalharacteristics suspicious for Shwachman-Diamond syndrome, this disorder should beuded by pancreatic isoamylase testing or gene mutation analysis (note: pancreaticylase testing is not useful in children <3). Other testing per center may bed to exclude IBMFS.2. Clonal cytogenetic abnormalities or Fluorescence In-Situ Hybridization (FISH) patternwith pre- myelodysplastic syndrome (pre-MDS) or MDS on marrow examination.3. Known severe allergy to ATG.. 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 isuspicion 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 carcinomau.10. Disease modifying treatment prior to study enrollment, including but not limited touse of androgens, eltrombopag, romiplostim, or immune suppression. Note: Supportiveures such as G-CSF, blood transfusion support and antibiotics are allowable
Updated on
05 May 2024.
Study ID: IRB-2020-0438
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