Vorinostat for Graft-versus-host Disease (GVHD) Prevention in Non-Malignant Adolescent and Young Adults (AYA) Population

Inclusion Criteria:

* Non-malignant condition amenable to transplantation, including but not limited to:

  1. Primary Immunodeficiency/Primary Immune regulatory disorders
  2. Inborn errors of metabolism
  3. Red blood cell disorders including hemoglobinopathies per protocol.
  4. Inherited bone marrow failure syndromes
* Available donor per protocol (matched siblings and matched unrelated donors, haploidentical donors). The use of mismatched unrelated donors will not be allowed for this study.
* Patient and/or legal guardian have signed the informed consent document
* Adequate organ function and performance status for allogeneic hematopoietic stem cell transplantation as defined by institutional practice:

  1. Pulmonary Function: diffusing capacity of the lungs for carbon monoxide (DLCO), forced expiratory volume in the first second (FEV1), Forced vital capacity (FVC) ≥50% predicted.
  2. Renal Function: Estimated or actual glomerular filtration rate (GFR) of ≥50 milliliters per minute (mL/min)/1.72 square meter (m2)
  3. Liver Function: aspartate aminotransferase (AST), alanine aminotransferase (ALT) \<3x upper limit of normal; total bilirubin ≤2.5 milligrams per deciliter (mg/dL) unless related to disease or Gilbert syndrome. There is no upper limit for bilirubin in patients with confirmed Gilbert syndrome.
  4. Cardiac Function: Ejection fraction (EF) ≥50% or fractional shortening (FS) ≥26%
  5. Performance Status: Karnofsky/Lansky score ≥70%(HIV) and Human T-lymphotropic virus type (HTLV) I/II negative
  6. Infectious Disease testing: human immunodeficiency virus
* Patients with transfusion-dependent anemias (per protocol) should have a liver MRI to document hepatic iron content (certain values will be excluded)
* All patients of childbearing age must agree to practice 2 effective methods of contraception at the same time or agree to abstinence for 6 months after the last dose for females. Males with female sexual partners of reproductive potential should use contraception during treatment and for at least 3 months after the last dose.
* Patients treated with other investigational therapies for underlying disorder must discontinue these therapies prior to enrollment on the study unless, in the opinion of the treating physician, discontinuing these therapies prior to transplant would place the patient at undue risk of morbidity or mortality. In this case, patients must discontinue investigational therapies prior to initiation of the conditioning regimen.

Exclusion Criteria:

\- Previous diagnosis of Fanconi anemia, dyskeratosis congenita or other telomere biology disorders, inherited genetic conditions known to adversely affect DNA-repair, or other disorders with known chemo- or radiosensitivity.

Additional testing may be conducted per investigator discretion but is not required for enrollment.

* Diagnosis of idiopathic severe aplastic anemia
* Diagnosis of severe combined immunodeficiency syndrome
* Diagnosis of malignancy within the last 5 years.
* Diagnosis of Epstein-Barr virus (EBV)-driven lymphoproliferative disorder within the last 5 years
* Uncontrolled bacterial, viral, or fungal infection at the time of enrollment
* Seropositive for HIV or HTLV
* Active hepatitis B or C
* Female patients that are pregnant or breast-feeding
* Inability to take oral medications.
* History of allergy to Vorinostat, related compounds, or any drugs used as part of the conditioning regimen or GVHD prophylaxis.
* Patients with transfusion-dependent anemia (≥8 packed red blood cell (PRBC) transfusions/year or ≥20 lifetime transfusions) that have a liver iron content of \>8 milligram (mg) Iron(Fe)/Gram dry weight or evidence of bridging fibrosis or cirrhosis on biopsy.
* Patients enrolled on another GVHD-prevention clinical trial.
* Patients receiving an ex-vivo T cell-depleted or cluster of differentiation (CD34)-selected stem cell graft.
* Subjects that have had prior treatment with a histone deacetylase inhibitor (e.g. vorinostat, valproic acid) within the last 30 days.
* History of prolonged corrected QT interval (QTc) syndrome.
* Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements