Pacritinib, Sirolimus, and Tacrolimus in Preventing Graft Versus Host Disease in Patients with Blood Cancer Undergoing Donor Stem Cell Transplant

Inclusion Criteria

• Patients must have an available 8/8 HLA-A, -B, -C, and -DRB1 matched-related or unrelated donor allogeneic hematopoietic peripheral blood stem cell graft
• Signed informed consent
• Acute myeloid leukemia, myelodysplasia, acute lymphoblastic leukemia, chronic myeloid leukemia, chronic lymphocytic leukemia, myeloproliferative neoplasms, Hodgkin lymphoma, or non-Hodgkin lymphoma requiring a matched allogeneic HSCT
• Acute leukemia (acute myeloid leukemia [AML] or acute lymphoblastic leukemia [ALL]) must be in complete remission defined as: < 5% marrow blasts with no morphologic evidence of leukemia, no peripheral blasts, marrow > 20% cellular, and peripheral absolute neutrophil count > 1000/uL (platelet recovery is not required)
• Myelodysplasia (MDS) and chronic myeloid leukemia (CML): must have < 5% marrow blasts
• Myeloproliferative neoplasms (MPN): must have < 5% peripheral / marrow blasts * Note: Prior use of a Janus kinase 2 (JAK2) inhibitor is allowed up to 4 weeks before day 0 of allogeneic hematopoietic cell transplantation (alloHCT)
• Hodgkin and non-Hodgkin lymphoma: must have a complete or partial response with prior therapy
• Left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition scan (MUGA) scan or echocardiogram (ECHO)
• Forced expiratory volume 1 (FEV1), forced vital capacity (FVC), and adjusted diffusing capacity of the lungs for carbon monoxide (DLCO) >= 50% of predicted values on pulmonary function tests
• Transaminases (aspartate aminotransferase [AST], alanine aminotransferase [ALT]) < 2 times upper limit of normal values
• Creatinine clearance >= 50 cc/min
• Performance status: Karnofsky performance status score >= 80%
• DONOR ELIGIBILITY
• Eligible donors will include healthy sibling, relative or unrelated donors that are matched with the patient at HLA-A, B, C, and DRB1 by high resolution typing as defined by the Collaborative Trials Network

Exclusion Criteria

• Active infection not controlled with appropriate antimicrobial therapy
• History of human immunodeficiency virus (HIV), hepatitis B, or active hepatitis C infection
• Anti-thymocyte globulin, alemtuzumab, bortezomib, or post-transplant cyclophosphamide as part of GVHD prophylaxis
• Sorror’s co-morbidity factors with total score > 4
• Any patient anticipating or scheduled to receive a tyrosine kinase inhibitor, FLT3 inhibitor, or JAK2 inhibitor (outside of this study) post-HCT
• Corrected QT interval (QTc) > 450 ms per Fridericia’s correction
• Thrombin time (TT), prothrombin time (PT), or partial thromboplastin time (PTT) > 2 x upper limit of normal
• Grade 3 or higher recent (within the past 6 months) or ongoing cardiac dysrhythmias, family history of long QT syndrome, or serum potassium < 3.0 mEq/L that is persistent and refractory to correction
• Grade 3 or higher recent (within the past 6 months) or ongoing bleeding events
• Symptomatic or uncontrolled cardiovascular disease, myocardial infarction or severe/unstable angina within the past 6 months, or New York Heart Association class III or IV congestive heart failure