Atorvastatin as GVHD Prophylaxis for Allogeneic Hematopoietic Cell Transplantation
Condition: Graft vs Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Atorvastatin calcium
Intervention description: 40 mg PO daily
Intervention MeSH terms: Atorvastatin; Calcium
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 69.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Graft vs Host Disease; GVHD; Allogeneic hematopoietic stem cell transplantation; HSCT; Atorvastatin

Summary:

      Hematopoietic stem cell transplantation is a procedure in which a person receives blood
      forming stem cells from a person called a "donor." The stem cells can be obtained from the
      hollow part of the hip bone or from blood.

      A serious problem with this treatment is graft-versus-host disease (GVHD). This happens when
      stem cells from the donor attack normal cells of the recipient. Currently, there is no
      universal standard of care in the United States to prevent GVHD.

      This study is being done to see if a medicine that is used to lower cholesterol can also help
      in reducing GVHD.

      Patients will receive atorvastatin daily by mouth starting 14 days before stem cell
      transplant. They will continue to take atorvastatin until 180 days after transplant. This
      medicine may be stopped earlier if there is a bad side effect or a severe GVHD. Patients will
      also receive standard treatment to prevent GVHD. Patients will undergo many tests that are
      standard for their treatment at West Virginia University (WVU), including blood tests to
      check blood counts, kidney function and HIV status; blood test to check for pregnancy; Multi
      Gated Acquisition Scan (MUGA scan)or echocardiogram to test heart function; lung function
      testing; and bone marrow aspirate or biopsy. Patients will also have the option to provide
      blood samples for optional research related to the study.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with a history of a hematological malignancy or bone marrow failure syndrome
             suitable for allogeneic stem cell transplantation in the opinion of treating
             transplant physician.

          -  Patients aged 18-75 years of age are eligible. Patients with age > 18 and ≤ 50 years
             will be eligible for myeloablative conditioning (MAC), while patients > 50 years of
             age, or those with previous history of autologous transplantation, high hematopoietic
             cell transplant comorbidity index (HCT-CI) score (>2), and baseline diagnosis of
             hodgkin's lymphoma, chronic lymphocytic leukemia and follicular lymphoma will be
             suitable for reduced intensity conditioning (RIC) transplantation (however intensity
             of conditioning regimen will remain at the discretion of treating physician).

          -  All patients must have at least one suitable human leukocyte antigen (HLA)-matched
             sibling or unrelated donor according to transplant center's guidelines (for selection
             of appropriate sibling donor).

          -  Patient must provide informed consent.

          -  Left ventricular ejection fraction ≥ 40%.

          -  Bilirubin ≤ 2 x the upper limit of normal (ULN) and aspartate aminotransferase (AST),
             and alanine aminotransferase (ALT) ≤ 3 x ULN; and absence of hepatic cirrhosis. For
             patients with Gilbert's syndrome, bilirubin ≤ 3 x ULN is permitted.

          -  Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal
             calculated by Cockcroft-Gault equation.

          -  Carbon monoxide diffusing capacity (DLCOcor) corrected for hemoglobin or forced
             expiratory volume at one second (FEV1) or DL/VA ≥ 40% of predicted (a pulmonary
             function test).

          -  Karnofsky performance status > 70.

          -  A negative pregnancy test will be required for all women of child bearing potential.
             Breast feeding is not permitted.

          -  Patients with positive HIV serology are eligible.

          -  Patients who have previously been taking atorvastatin or any other statin drug will be
             eligible as long as there is no contraindication to switch to atorvastatin (40mg/day)
             in the opinion of the treating physician.

          -  Method of stem-cell collection from the sibling donor will be at the discretion of the
             treating physician. Although it is anticipated that majority of sibling donors will
             undergo Granulocyte colony-stimulating factor(G-CSF) induced stem cell mobilization;
             however donors undergoing bone marrow harvest or stem cell mobilization with
             experimental agents (e.g. plerixafor) will remain eligible for the study.

        Exclusion Criteria:

          -  Uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart
             failure.

          -  Evidence of active bacterial, viral or fungal infection at the time of transplant
             conditioning.

          -  History of intolerance or allergic reactions with atorvastatin will not be eligible.

          -  Undergoing a T-cell depleted allogeneic transplantation

          -  Receiving conditioning regimens containing anti-thymocyte globulin, and/or campath