Atorvastatin for the Prophylaxis of Acute GVHD in Patients Undergoing Matched Sibling Allogeneic Transplantation
Condition: Graft vs Host Disease
MeSH terms: Graft vs Host Disease
Intervention: Atorvastatin calcium (Lipitor)
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: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: HSCT; HPC; HCT; BMT; lipitor; atorvastatin; HMG-CoA Reductase Inhibitor; Hematopoietic stem cell transplant; allogeneic transplant; GVHD; graft-versus-host-disease; Graft vs Host Disease

Summary:

      Atorvastatin for prevention of acute GVHD
    

Eligibility criteria:

        DONOR ELIGIBILITY CRITERIA:

          1. Donors must be ≥18 years of age, and willing/able to provide informed consent.

          2. Female donors of child-bearing potential should have a negative pregnancy test, and
             must be not be breast feeding.

          3. Adequate hepatic function with bilirubin, AST and ALT < 2.5 x upper limit of normal.

          4. Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal
             calculated by Cockcroft-Gault equation.

          5. Adequate cardiac function as per institutional guidelines.

          6. Donors with positive HIV serologies are not eligible.

          7. No clinical evidence of uncontrolled active bacterial, viral or fungal infection at
             the time of stem cell mobilization.

          8. Donors must have a Karnofsky performance score of ≥60.

          9. Donors with history of intolerance or allergic reactions with atorvastatin will not be
             eligible. Hypersensitivity to any component of atorvastatin.

         10. 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 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.

        PATIENT ELIGIBILITY CRITERIA:

          1. Patients with a history of a hematological malignancy or bone marrow failure syndrome
             suitable for matched sibling allogeneic stem cell transplantation in the opinion of
             treating transplant physician.

          2. 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).

          3. All patients must have at least one suitable HLA-matched sibling donor according to
             transplant center's guidelines (for selection of appropriate sibling donor).

          4. Patient must provide informed consent.

          5. Left ventricular ejection fraction > 40%. No uncontrolled arrhythmias or uncontrolled
             New York Heart Association class III-IV heart failure.

          6. Bilirubin <2mg/dl and AST and ALT < 3 x normal; and absence of hepatic cirrhosis.

          7. Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal
             calculated by Cockcroft-Gault equation.

          8. DLCO (diffusion capacity; corrected for hemoglobin) ≥ 50% of predicted.

          9. Karnofsky performance status > 70.

         10. A negative pregnancy test will be required for all women of child bearing potential.
             Breast feeding is not permitted.

         11. Patients with positive HIV serology are not eligible.

         12. No evidence of active uncontrolled bacterial, viral or fungal infection at the time of
             transplant conditioning.

         13. Patients with history of intolerance or allergic reactions with atorvastatin will not
             be eligible.

         14. 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.

         15. Patients undergoing a T-cell depleted allogeneic transplantation will not be eligible.

         16. Patients receiving conditioning regimens containing antithymocyte globulin, and/or
             campath will not be eligible.