A Study of Tacrolimus/Methotrexate and Tocilizumab to Prevent Acute Graft-Versus-Host Disease (AGVD) After Allogeneic Hematopoietic Stem Cell Transplant
Condition: Hematopoietic Stem Cell Transplantation
MeSH terms: Graft vs Host Disease
Intervention: Tacrolimus; Methotrexate; Tocilizumab
Intervention description: Patients enrolled in the clinical trial will receive tacrolimus per institutional guidelines at doses to maintain therapeutic levels and continued until at least Day 90 posttransplant.; Methotrexate will be dosed at 15 mg/m2 Day +1 and 10mg/m^2 Days +3, +6 and +11.; Tocilizumab will be administered intravenously at a dose of 8 mg/kg at Day -1.
Intervention MeSH terms: Methotrexate; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a phase II open label trial designed to evaluate the efficacy of Tac/MTX/Toc in
      preventing graft versus host disease (GVHD). Outcomes of patients on this clinical trial will
      be compared to those of contemporary controls from the CIBMTR.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age ≥18 years

          2. Patients with acute leukemia, chronic myelogenous leukemia, myeloproliferative disease
             and myelodysplasia with less than 5% of blasts in the bone marrow

          3. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, Non-Hodgkin
             Lymphoma or Hodgkin Disease with chemosensitive disease at time of transplant

          4. Planned conditioning regimens including combination of busulfan and fludarabine or
             busulfan and cyclophosphamide

          5. Transplantation with T-cell-replete grafts

          6. Bone marrow or mobilized peripheral blood cell grafts

          7. Patients must have either a sibling donor (6/6 match at human leukocyte antigens
             (HLA-A, -B and -DRB1) or a unrelated donor (8/8 match at HLA-A, -B, -C and -DRB1)

          8. Cardiac function: Ejection fraction at rest >45% for myeloablative conditioning or
             >40% for reduced intensity conditioning

          9. Estimated creatinine clearance greater than 50 mL/minute (using the Cockcroft-Gault
             formula and actual body weight)

         10. Pulmonary function: Diffusing Capacity of Lung for Carbon Monoxide (DLCO) ≥40%
             (adjusted for hemoglobin) and FEV1≥50%

         11. Liver function: total bilirubin < 1.5 x the upper limit of normal and alanine
             aminotransferase (ALT) / aspartate aminotransferase (AST) < 2.5x the upper normal
             limit

         12. Signed informed consent

        Exclusion Criteria:

          1. Prior allogeneic hematopoietic cell transplant (HCT)

          2. Karnofsky Performance Score <70%

          3. Patients with uncontrolled bacterial, viral or fungal infections (currently taking
             medication and with progression of infectious disease or no clinical improvement) at
             time of enrollment

          4. Prior intolerance or allergy to Tocilizumab

          5. Use of rituximab, alemtuzumab, anti-thymocyte globulin (ATG) or other monoclonal
             antibody at time of conditioning regimen

          6. History of diverticulitis, Crohn's disease or ulcerative colitis

          7. History of demyelinating disorder

          8. Pregnant and lactating women

          9. Patients with a history of rheumatologic disorders who have previously received
             Tocilizumab

        Eligibility for the Control Arm

        Patients in the control arm will be identified from patients reported to the CIBMTR from
        U.S centers. Control patients will be required to satisfy similar eligibility requirements
        as patients being enrolled in the clinical trial. Patients will need to fulfill the same
        inclusion criteria for the clinical trial according to Section 2.4.1, plus the following:

          1. Receive Tac/MTX as the sole GVHD prophylaxis approach

          2. Receive the same regimens as specified in Table 2.5

          3. Year of transplant from 2010 to 2013

        Exclusion criteria for the controls:

        1. Karnofsky Performance Score < 70%

        Data for all eligible patients will be used to constitute the control database for this
        study