Unrelated And Partially Matched Related Donor PSCT w/ TCR αβ Depletion for Patients With BMF

This is a single arm pilot study using TCR alpha/beta+ T cell-depleted peripheral blood stem
cells (PBSC) from closely matched unrelated donors or partially matched/haploidentical
related donors for hematopoietic stem cell transplant (HSCT) in patients with acquired and
inherited bone marrow failure (BMF) syndromes. Previously established, disease-specific
transplant preparative regimens will be administered based on the specific underlying BMF
condition. Mobilized PBSC will be processed using the CliniMACS system for TCR alpha/beta+ T
cell depletion plus CD19+ B cell depletion. The study will determine efficacy of this
strategy in terms of engraftment, rates of acute and chronic Graft versus Host Disease
(GvHD), and one year overall and event-free survival.

Inclusion Criteria:

- Acquired and Inherited Bone Marrow Failure Conditions Associated with Trilinear Bone
Marrow Failure

- Acquired Aplastic Anemia

- Paroxysmal Nocturnal Hemoglobinuria

- Fanconi Anemia

- Dyskeratosis Congenita and related telomere disorders

- Shwachman-Diamond Syndrome

- Inherited Bone Marrow Failure Conditions Associated with Predominant Single Lineage
Failure

- Severe Congenital Neutropenia

- Isolated disorders of erythropoiesis

- Congenital Thrombocytopenia Syndromes

- Organ function status

- Renal: Serum creatinine <1.5x upper limit of normal for age

- Hepatic: Transaminases <5x upper limit of normal. Bilirubin <2.0 mg/dL, (unless
elevation due to Gilberts disease or known hemolytic anemia).

- Cardiac: shortening fraction >27%

- Pulmonary: Diffusing Capacity (DLCO) >50% predicted in patients old enough to
comply with pulmonary function testing (PFTs) or no baseline oxygen requirement
for younger patients.

- Lansky or Karnofsky performance >60

- Infectious disease criteria

- No active, untreated infections

- Patients with likely bacterial infections must be receiving appropriate
antibacterial therapy and demonstrating therapy response

- Patients with likely fungal infections must have had at least 2 weeks of
appropriate anti-fungal antibiotics and be asymptomatic.

- Patients with symptoms consistent with active viral infection will be deferred
until viral symptoms resolve. Patients with evidence of cytomegalovirus (CMV),
Epstein-Barr virus (EBV) or other known viremia must receive appropriate therapy
to clear viremia prior to initiating study therapy.

- Signed consent by parent/guardian or able to give consent if >18 years

Exclusion Criteria:

- Patients who do not meet disease, organ or infectious criteria.

- Patients with a clinical diagnosis of myelodysplastic syndrome (MDS) defined by
combination of bone marrow dysplasia and classic cytogenetic lesion (Monosomy 7,
Trisomy 8 eg.), with or without excess blasts.

- Patients with no suitable closely Human leukocyte antigen (HLA)-matched unrelated or
related haploidentical matched donor available. Patients with suitable fully matched
related donor are also not eligible.

- Pregnant females. All females of childbearing potential must have negative pregnancy
test.

Donor selection and eligibility:

• Donor selection will comply with 21 CFR 1271* of the U.S. Food and Drug Administration's
Code of Federal Regulations

Donor testing:

- Unrelated donor meets National Marrow Donor Program criteria for donation

- For partially matched related donors, Children's Hospital of Philadelphia (CHOP) bone
marrow transplant (BMT) standard procedures apply for determining donor eligibility,
including donor screening and testing for relevant communicable disease agents and
diseases. The donor collection program accredited.

- For partially matched related donors, if subject has genetically confirmed iBMF
syndrome, related donor must be evaluated for this disorder and testing must be
negative

- Infectious disease testing of donor will be per current Blood and Marrow Transplant
Program Standards of Practice as per 21 CFR Part 1271. Donor medical records and
history are reviewed to confirm that the donor is free of infectious risk factors and
meets donor eligibility criteria as defined by 21 CFR 127.