Sitagliptin for Prevention of Acute Graft Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation

INCLUSION CRITERIA

A. Patients with any of the following hematologic malignancies:

• Acute myeloid leukemia (AML) with any of the following:
• In first remission (CR1) with intermediate risk or high-risk cytogenetic and/or molecular features.
• Patients in second or subsequent complete remission (CR2, CR3, etc.).
• Primary refractory or relapsed AML with no more than any one of the following adverse additional features according to modified CIBMTR criteria:49
• Duration of first CR 25% at time of enrollment
• Age >40 years
• Myelodysplasia with any of the following features:
• Refractory anemia with excess blasts type I (5-10% blasts) or II (11-20% blasts) in the bone marrow (RAEB I and II)
• Refractory cytopenia with multilineage dysplasia (RCMD) and poor risk cytogenetics (i.e., chromosome 7 abnormalities or complex karyotype with at least 3 abnormalities per clone)
• Chronic myelogenous leukemia (CML) with one of the following criteria:
• Accelerated phase, defined by any of the following:
• Blasts 10-19% in peripheral blood white cells or bone marrow
• Peripheral blood basophils at least 20%
• Persistent thrombocytopenia ( 1000 x 109/l) unresponsive to therapy
• Increasing spleen size and increasing white blood cell (WBC) count unresponsive to therapy
• Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase)
• Chronic phase provided a complete hematologic remission was not achieved by 3 months or a complete cytogenetic remission by 18 months and the patient had received at least 2 tyrosine kinase inhibitors
• Patients with aggressive non-Hodgkin's lymphoma (NHL), including diffuse large cell lymphoma, mediastinal B-cell lymphoma, transformed lymphoma, mantle cell lymphoma, and peripheral T cell lymphoma, who also have one of the following criteria:
• Failure to achieve complete remission to primary induction therapy
• Relapsed and refractory to at least one line of salvage systemic therapy
• Failed stem cell collection
• Patients with Hodgkin's lymphoma meeting one of the following criteria:
• Primary refractory (failure to achieve complete remission to primary induction therapy)
• Relapsed and refractory to at least one line of salvage systemic therapy
• Failed stem cell collection

B. Patient age ≥ 18 to ≤ 60 years

C. Karnofsky Performance status ≥ 70%

D. Patients must also receive a full myeloablative preparative regimen (Patients treated with either total body irradiation (TBI)-based or high-dose chemotherapy only regimens are eligible other than high-dose busulfan containing regimens or regimens that include anti-thymocyte globulin or other T cell depleting antibodies)

E. Patients receiving allogeneic peripheral blood stem cell (PBSC) grafts from HLA-matched (5/6 and 6/6 matches) siblings or from well matched unrelated donors (9/10 or 10/10 matches at HLA-A, B, C, DRB1 and DQB1 by high resolution typing) are included. All grafts will be unmanipulated (i.e., no T cell depleted or CD34 selected grafts).

F. No uncontrolled bacterial, viral or fungal infection at time of enrollment defined as currently taking medication and progression of clinical symptoms

G. No HIV disease (Patients with immune dysfunction are at a significantly higher risk of infection from intensive immunosuppressive therapies)

H. Non-pregnant and non-nursing

I. Required baseline values within 60 days prior to admission:

• LVEF ≥ 45%
• DLCO ≥ 50% of predicted (corrected for hemoglobin)

J. Required baseline laboratory values within 16 days prior to admission:

• Estimated creatinine clearance ≥60 ml/min
• Serum total bilirubin ≤ 2 x upper limit of normal value (ULN)
• AST and ALT ≤ 2 x ULN (unless determined by treating physician to be related to underlying malignancy)

K. Signed written informed consent (Patient must be capable of understanding the investigational nature, potential