Visilizumab for the Prevention of Graft-versus-Host Disease After Allogeneic Hematopoietic Cell Transplantation
Condition: Graft Versus Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Visilizumab; Tacrolimus; Methotrexate; Antithymocyte globulin (ATG); Tacrolimus; Methotrexate
Intervention description: 3 mg/m^3, IV (in the vein) on day 0, prior to hematopoietic cell infusion (transplant).; 0.02 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 4 after transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.; 15 mg/m^2 intravenously (IV) on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.; 1 mg/kg IV over 6 hours on Day 3 before transplant; 3.25 mg/kg IV over 4 hours on days 2 and 1 before transplant.; 0.03 mg/kg/24h (based on ideal body weight) continuous infusion (over 24 hours) beginning on day 3 before transplant up to approximately day 180 after transplant. Switch to oral tacrolimus as able. Dose adjusted based on levels. In the absence of GVHD, the dose to be tapered beginning 100 days after transplant.; 15 mg/m^2 IV on Day 1 after transplant; 10 mg/m^2 IV on Days 3, 6 and 11 after transplant.
Intervention MeSH terms: Methotrexate; Tacrolimus; Thymoglobulin; Antilymphocyte Serum; Visilizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: graft versus host disease; GVHD; allogeneic transplant; GVHD prevention; unrelated donors; mismatched unrelated donors; hematological malignancies; Leukemia; Lymphoma; Myelodysplastic Syndrome; Myelofibrosis; Aplastic Anemia; Multiple Myeloma

Summary:

      The purpose of this study was to test whether a new drug named visilizumab would decrease the
      severity of graft-versus-host disease in patients treated with a mismatched donor.
      Investigators planned to use visilizumab in combination with tacrolimus and methotrexate as
      the "study treatment".
    

Eligibility criteria:

        Inclusion Criteria:

          -  One of the following diagnoses with histological confirmation by the Pathology
             Department at H. Lee Moffitt Cancer Center:

          -  Acute Lymphocytic Leukemia (ALL) in complete remission 1 (CR1) with t(9:22) or
             t(4:11), or any ALL beyond CR1

          -  Acute Myelogenous Leukemia (AML) with high risk cytogenetics in CR1 as defined by
             Bloomfield any AML beyond CR1

          -  Myelodysplastic Syndrome (MDS) with International Prognostic Scoring System (IPSS)
             score > 1

          -  Chronic myelomonocytic leukemia (CMML)

          -  Chronic Myelogenous Leukemia (CML) with Imatinib-refractory chronic phase, or beyond
             chronic phase by morphology or cytogenetics

          -  Myelofibrosis

          -  Severe aplastic anemia

          -  Chemosensitive Non-Hodgkin's lymphoma and Hodgkin's disease that are not candidate to
             autologous transplant due to prior autologous transplantation

          -  Multiple Myeloma patient not candidate for autologous stem cell transplantation

          -  Karnofsky performance status ≥ 70% (adult)

          -  Normal organ and marrow function as defined below:

          -  Hepatic: Total bilirubin must be less than or equal to 2mg/dL (Gilbert and other
             syndromes with increased indirect bilirubin are allowed); serum transaminases must be
             less than two times the upper limit of normal

          -  Pulmonary: diffusing capacity of lung for carbon monoxide (DLCO) (corrected for Hgb),
             forced expiratory volume-one second (FEV1), forced vital capacity (FVC) must be
             greater than 50% predicted

          -  Cardiac: Left ventricular ejection fraction at rest must be greater than 50%

          -  Renal: Creatinine clearance (measured or calculated) must be equal or greater than 50
             ml/min/1.73m^2

        Exclusion Criteria:

          -  Anti thymocyte globulin (ATG) or anti T cell therapy in prior 45 days

          -  Splenectomized patients;

          -  A positive pregnancy test administered to all females of childbearing potential prior
             to allogeneic stem cell transplant

          -  Inability to comply with follow up as determined by the patient's physician

          -  HIV-I/II infection prior to hematopoietic stem cell (HSC) transplantation, confirmed
             by nucleic acid test (NAT)

          -  Uncontrolled bacterial or fungal infection

          -  History of documented invasive aspergillosis or cytomegalovirus (CMV) pneumonia

          -  Presence of any of the following comorbid conditions:

          -  History of myocardial infarction

          -  Congestive heart failure (even if symptomatically controlled)

          -  Peripheral vascular disease (including intermittent claudication or history of bypass
             for arterial insufficiency)

          -  Untreated thoracic or abdominal aneurysm (6cm or more)

          -  History of any cerebrovascular accident including transient ischemic attacks

          -  Dementia

          -  History of peptic ulcer disease requiring treatment

          -  Connective tissue/rheumatologic disorders

          -  Diabetes unless being managed with dietary changes only

          -  Hemiplegia/paraplegia

          -  History of solid tumor excluding skin or cervical carcinoma after curative resection