Ensayos clínicos

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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Eligibility last updated 4/10/23. Questions regarding updates should be directed to the study team contact.