In Vivo Treg Expansion and Graft-Versus-Host Disease Prophylaxis
Condition: Graft-Versus-Host-Disease
MeSH terms: Graft vs Host Disease
Intervention: IL-2; Tacrolimus; Sirolimus
Intervention description: A subcutaneous injection will be administered 3 times a week (separated by at least 1 day between injections), from day 0 to +90 (+/- 7 days).; Will be administered at 0.01 mg/kg/day (based on ideal body weight) continuous IV infusion or equivalent oral dosing starting on day -3; Orally on day -1. The dose for loading is 12 mg by mouth (PO)
Intervention MeSH terms: Sirolimus; Aldesleukin; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 20.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: GVHD; Allogeneic; Hematopoietic Cell Transplant

Summary:

      IL-2 add-back post allogeneic hematopoietic stem cell transplant (HSCT), combined with
      Sirolimus (SIR), Tacrolimus (TAC) will optimize Treg reconstitution and prevent graft versus
      host disease (GVHD).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have an available 8/8 human leukocyte antigen (HLA)-A, -B, -C, and -DRB1
             matched-related or unrelated donor allogeneic hematopoietic peripheral blood stem cell
             graft.

          -  Acute myeloid leukemia, myelodysplasia, acute lymphoblastic leukemia, chronic myeloid
             leukemia, or myeloproliferative neoplasms requiring a matched allogeneic HSCT.

               -  Acute Leukemia (AML or 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/µL (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.

          -  Adequate vital organ function:

               1. Left ventricular ejection fraction (LVEF) ≥ 45% by multi gated acquisition (MUGA)
                  scan or ECHO

               2. Forced expiratory volume at one second (FEV1), forced vital capacity (FVC), and
                  adjusted diffusing lung capacity oxygenation (DLCO) ≥ 50% of predicted values on
                  pulmonary function tests

               3. Transaminases (AST, ALT) < 2 times upper limit of normal values

               4. 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.

        Exclusion Criteria:

          -  Active infection not controlled with appropriate antimicrobial therapy

          -  History of HIV, hepatitis B, or hepatitis C infection

          -  Anti-thymocyte globulin, alemtuzumab, bortezomib, or cyclophosphamide administered
             within 14 days before or planned to receive with HCT conditioning or as part of GVHD
             prophylaxis in the 14 days after HCT.

          -  Hypersensitivity to recombinant human IL-2

          -  Chronic lymphocytic leukemia, Hodgkin lymphoma, and non-hodgkin lymphoma are excluded
             as these malignancies may express the IL-2 receptor and pose a potential growth signal
             to any present disease.

          -  Sorror's co-morbidity factors with total score >4