Adding Itacitinib to Cyclophosphamide and Tacrolimus for the Prevention of Graft Versus Host Disease in Patients Undergoing Hematopoietic Stem Cell Transplants

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorizedrepresentative

• Assent, when appropriate, will be obtained per institutional guidelines

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

• If unavailable, exceptions may be granted with study principal investigator (PI) approval

• Age: =< 80 years

• Note: Patients > 70 years of age must have Karnofsky performance status >= 80and HCT-comorbidity index (CI) =< 2

• Karnofsky performance status >= 70%

• Patients with the following diagnosis, eligible to undergo allogeneic HCT from an 8/8 match related/unrelated donor (A, B, C, DR by high resolution typing)

• Acute leukemias (acute myeloid leukemia [AML] or acute lymphoblastic leukemia [ALL]) in complete remission with bone marrow (BM) blast of < 5%

• Myelofibrosis (MF): Primary or secondary with high- or intermediate-2 risk perDynamic International Prognostic Scoring System (DIPSS)

• Myelodysplastic syndrome (blast < 10%)

• Myeloproliferative neoplasm (MPN) other than MF needing HCT

• Chronic myelomonocytic leukemia (CMML)

• Total bilirubin =< 2 x upper limit of normal (ULN) (unless has Gilbert's disease) (within 30 days prior to day 1 of protocol therapy unless otherwise stated)

• Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvatetransaminase (SGPT) < 5 x ULN (within 30 days prior to day 1 of protocol therapyunless otherwise stated)

• Creatinine clearance of >= 60 mL/min per 24 hour urine test or the Cockcroft-Gaultformula (within 30 days prior to day 1 of protocol therapy unless otherwise stated)

• Left ventricular ejection fraction (LVEF) >= 50%

• Note: To be performed within 30 days prior to day 1 of protocol therapy

• If able to perform pulmonary function tests: forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and diffusion capacity of the lungs for carbonmonoxide (DLCO) (diffusion capacity) >= 50% of predicted (corrected for hemoglobin) (within 30 days prior to day 1 of protocol therapy)

• If unable to perform pulmonary function tests: O2 saturation > 92% on room air (within 30 days prior to day 1 of protocol therapy)

• Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab)combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigennegative), and syphilis rapid plasma reagin (RPR) (within 30 days prior to day 1 ofprotocol therapy)

• If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performedOR

• If seropositive for HIV, HCV or HBV, nucleic acid quantitation must beperformed. Viral load must be undetectable

• Meets other institutional and federal requirements for infectious disease titerrequirements

• Note: Infectious disease testing to be performed within 28 days prior to day 1of protocol therapy

• Women of childbearing potential (WOCBP): negative urine or serum pregnancy test (within 30 days prior to day 1 of protocol therapy)

• If the urine test is positive or cannot be confirmed as negative, a serumpregnancy test will be required

• Agreement by females and males of childbearing potential to use an effective methodof birth control or abstain from heterosexual activity for the course of the studythrough at least 6 months after the last dose of protocol therapy

• Childbearing potential defined as not being surgically sterilized (men andwomen) or have not been free from menses for > 1 year (women only)

Exclusion Criteria:

• Prior allogeneic HCT

• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 daysprior to day 1 of protocol therapy

• Note: Conditioning regimen within 21 days prior to day 1 of protocol therapy isnot considered as an exclusion criterion. Patients on maintenance chemotherapyare not excluded

• Other investigational drugs for treatment of GVHD

• History of allergic reactions attributed to compounds of similar chemical orbiologic composition to study agents

• Psychological issues, no appropriate caregivers identified, or non-compliant tomedication

• Clinically significant uncontrolled illness

• Uncontrolled infection (bacterial, viral, fungal)

• Other active malignancy

• Females only: Pregnant or breastfeeding

• Any other condition that would, in the investigator's judgment, contraindicate thepatient's participation in the clinical study due to safety concerns with clinicalstudy procedures

• Prospective participants who, in the opinion of the investigator, may not be able tocomply with all study procedures (including compliance issues related tofeasibility/logistics)