Study of Itacitinib for the Prophylaxis of Graft-Versus-Host Disease and Cytokine Release Syndrome After T-cell Replete Haploidentical Peripheral Blood Hematopoietic Cell Transplantation

Inclusion Criteria:

Patients must meet the following criteria within 30 days prior to Day 0 unless otherwise
noted.

- Diagnosis of a hematological malignancy listed below:

- Acute myelogenous leukemia (AML) in complete morphological remission (MRD
negative, based on International Working Group (IWG) Criteria)

- Acute lymphocytic leukemia (ALL) in complete morphological remission (MRD
negative, based on IWG Criteria)

- Myelodysplastic syndrome with less than 5% blasts in bone marrow.

- Non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) in 2nd or greater complete
or partial remission.

- Planned treatment is myeloablative or reduced intensity conditioning followed by T
Cell-replete peripheral blood haploidentical donor transplantation

- Available human leukocyte antigen (HLA)-haploidentical donor who meets the following
criteria:

- Blood-related family member who is either a sibling (full or half) or offspring).

**Other donors will be excluded, including: parent, cousin, niece or nephew, aunt
or uncle, and grandparent.

- At least 18 years of age

- HLA-haploidentical donor/recipient match by at least low-resolution typing per
institutional standards.

- In the investigator's opinion, is in general good health, and medically able to
tolerate leukapheresis required for harvesting hematopoietic stem cells (HSC).

- No active hepatitis.

- Negative for human T-cell lymphotrophic virus (HTLV) and human immunodeficiency
virus (HIV).

- Not pregnant.

- Safety Lead-In Phase: For the first three patients, the donor must consent to a
second product collection should it prove necessary.

- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

- Adequate organ function as defined below:

- Total bilirubin ≤ 2.5 mg/dl (unless the patient has a history of Gilbert's
syndrome).

- Aspartate aminotransferase (AST)(SGOT) and alanine aminotransferase (ALT) (SGPT)
≤ 3.0 x institutional upper limit of normal (IULN).

- Creatinine ≤ 2.0 x IULN OR estimated creatinine clearance ≥ 30 mL/min/1.73 m^2 by
Cockcroft-Gault Formula.

- Oxygen saturation ≥ 90% on room air.

- Left ventricular ejection fraction (LVEF) ≥ 40%.

- Forced expiratory volume (FEV1) and forced vital capacity (FVC) ≥ 40% predicted,
diffusing capacity of the lung for carbon monoxide (DLCOc) ≥ 40% predicted. If
DLCO is < 40%, patients will still be considered eligible if deemed safe after a
pulmonary evaluation.

- At least 18 years of age at the time of study registration

- Able to understand and willing to sign an Institutional Review Board (IRB) approved
written informed consent document (or that of legally authorized representative, if
applicable).

- Must be able to receive GVHD prophylaxis with tacrolimus, mycophenolate mofetil, and
cyclophosphamide

Exclusion Criteria:

- Must not have undergone a prior allogeneic donor (related, unrelated, or cord)
transplant. Prior autologous transplant is not exclusionary.

- Presence of donor-specific anti-HLA antibodies.

- Known HIV or active hepatitis B or C infection.

- Known hypersensitivity to one or more of the study agents, including Ruxolitinib and
Itacitinib.

- Must not have myelofibrosis or other disease known to prolong neutrophil engraftment
to > 35 days after transplant.

- Must not receive antithymocyte globulin as part of pre-transplant conditioning
regimens.

- Currently receiving or has received any investigational drugs within the 14 days prior
to the first dose of study drug (Day -3).

- Pregnant and/or breastfeeding.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, autoimmune disease, symptomatic congestive heart failure, unstable angina
pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that
would limit compliance with study requirements.

- Immunosuppressive doses of steroids. Subjects with steroids for adrenal insufficiency
will not be excluded.