Vorinostat for Graft vs Host Disease Prevention in Children, Adolescents and Young Adults Undergoing Unrelated Donor Blood and Marrow Transplantation

All subjects will undergo unrelated donor allogeneic blood and marrow transplant (BMT)
according to local site institutional practice. The preparative regimen will depend upon the
subject's underlying disease, previous therapy, and comorbidities. GVHD prophylaxis will
consist of standard post-transplant immunosuppression, including tacrolimus and methotrexate.
Vorinostat will be administered at 30, 45 or 60 mg/m2 BID PO from 10 days prior to transplant
(day -10), until day +100 post-transplant (110 total days of dosing).

Inclusion Criteria:

- A prospective patient for allogeneic BMT for hematologic conditions, both malignant
and nonmalignant. Donor must be unrelated marrow or peripheral blood cells. A patient
with history of CNS involvement is eligible if CNS disease is in remission at time of
study consideration.

- The donor and recipient must have an HLA-8/8 allelic match at the HLA-A, -B, -C, and
-DRB1. High resolution typing is required for all alleles.

- Diagnoses to be included:

1. Acute Myeloid Leukemia (AML) or Acute Lymphoblastic Leukemia (ALL) in first or
second remission. Remission is defined as the absence of blasts in the peripheral
circulation at the time of enrollment, < 5% blasts in the bone marrow and absence
of extramedullary disease including CNS involvement.

2. Chronic Myeologenous Leukemia (CML) in first or subsequent chronic phase failing
to respond (or intolerant) to at least two different tyrosine kinase inhibitors.
CML in accelerated or blast phase (CML-AP/BP) are eligible without requirement to
fail tyrosine kinase inhibitor therapy, but must be in remission at time of
enrollment. Remission is defined as the absence of blasts in the peripheral
circulation at the time of enrollment, <5% blasts in the bone marrow and absence
of extramedullary disease including CNS involvement.

3. Myelodysplastic syndrome (MDS) with intermediate or high-risk IPSS or equivalent
IPSSR score with < 10% blasts in the bone marrow.

4. Mature B Cell Malignancies (including Mantle Cell Lymphoma, Follicular Lymphoma.
Diffuse Large B Cell Lymphoma, Non-Hodgkin Lymphoma not otherwise
specified).Subjects should have extinguished standard of care options prior to
being considered eligible for this trial

- Subjects aged 3 to 21 years

- Karnofsky Performance Scale score of 70% or higher

- Life expectancy of greater than 6 months

- Subjects must have normal organ and marrow function (as defined in protocol)

- Ability to take oral medication and be willing to adhere to the vorinostat regimen

- For females of reproductive potential and men: The effects of vorinostat on the
developing human fetus are unknown. For this reason and because histone deacetylase
inhibitor agents as well as other therapeutic agents used in this trial (e.g.,
tacrolimus and methotrexate) are known to be teratogenic, women of child-bearing
potential and men must agree to use adequate contraception (hormonal or barrier method
of birth control; abstinence) prior to study entry, for the duration of study
participation and for 4 months after completion of vorinostat administration.

- Ability to understand and the willingness to sign a written informed consent document

- Stated willingness to comply with all study procedures and availability for the
duration of the Study

- For the cognitive assessment and patient-reported QOL exploratory correlative portion
of the study, subjects must speak, read and understand English. Subjects who do not
speak, read and understand English but satisfy all other inclusion criteria may still
participate in the study but will not complete the cognitive and QOL portions.

Exclusion Criteria:

- Subjects who are not a candidate for an unrelated donor allogeneic BMT based on the
current local site institutional BMT program clinical practice guidelines. Organ
function criteria will be utilized per the current local site institutional BMT
program clinical practice guidelines. There will be no restriction to study entry
based on hematological parameters.

- Subjects who are enrolled on another GVHD treatment or prevention trial.

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to vorinostat.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements. Subjects still under therapy for presumed or proven infection are
eligible provided there is clear evidence (radiographic findings and/or culture
results) that the infection is well-controlled. Subjects under treatment for infection
will be enrolled only after clearance from the PI.

- Pregnant women are excluded from this study because vorinostat is a histone
deacetylase inhibitor agent with the potential for teratogenic or abortifacient
effects. Because there is an unknown but potential risk for adverse events in nursing
infants secondary to treatment of the mother with vorinostat, breastfeeding should be
discontinued if the mother is treated with vorinostat. Should a woman become pregnant
or suspect she is pregnant while she or her partner is participating in this study,
she should inform her treating physician immediately.

- Subjects with evidence of HIV seropositivity and/or positive PCR assay, HTLV1/HTLV2
seropositivity. The safety of allogeneic HSCT is not yet well-established for this
population.

- Subjects with evidence of Hepatitis B or Hepatitis C PCR positivity. Hepatitis
reactivation following myelosuppressive therapy can lead to fatal complications.

- Subjects with a history of prolonged QTc syndrome.

- Subjects who have had prior treatment with a drug like vorinostat (i.e., valproic
acid) within the last 30 days.

- Subjects with documented evidence of cognitive impairment prior to enrollment on this
study (diagnosis of dementia, mild cognitive impairment, or other neurological
illnesses that impacts cognition) are excluded from the cognitive assessment portion
of the study only.