Phase II Trial Evaluating the Safety and Efficacy of Atorvastatin for the Prophylaxis of Acute Graft Versus Host Disease(GVHD) in Patients With Hematological Malignancies Undergoing HLA-Matched Related Donor Hematopoietic Stem Cell Transplantation (HSCT)
Donor Eligibility Criteria
- The donor must be at least 18 years of age, and willing/able to provide informed
consent. Complete medication list will be reviewed for potential negative interaction
- The donor must be an HLA-matched sibling or relative.
- Syngeneic donors are not eligible.
- Female donors of child-bearing potential should have a negative pregnancy test, and
must not be breast feeding.
- Bilirubin, AST and ALT must be < 2 x normal; and absence of hepatic
- Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal
calculated by Cockcroft-Gault equation.
- Adequate cardiac function with no history of congestive heart failure, uncontrolled
atrial fibrillation or ventricular tachyarrhythmias.
Patient Eligibility Criteria
- Have hematologic malignancy requiring allogeneic HSCT, have adequate organ function,
a serologic (or higher resolution) 6/6 class I human leukocyte antigen (HLA)-A and B
and molecular class II DRB1 matched related donor, and are able to give informed
- Patients > 18 and ≤ 65 years with comorbidity score ≤ 3 will be eligible for
myeloablative conditioning (MAC), while patients > 65 years of age, those with
previous history of autologous transplantation, or high comorbidity index (>3) will
be eligible for reduced intensity conditioning (RIC) transplantation .
- All patients must have at least one 6/6 HLA-matched sibling donor.
- Patient must provide informed consent
- Patients must have left ventricular ejection fraction > 30%, no uncontrolled
arrhythmias or New York Heart Association class III-IV heart failure.
- Bilirubin must be < 2 x normal; and absence of hepatic fibrosis/cirrhosis.
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be <2 x
normal; and absence of hepatic fibrosis/cirrhosis.
- Serum creatinine clearance of ≥40% of normal calculated by Cockcroft-Gault equation.
- Forced expiratory volume in one second (FEV1)and diffusion capacity; corrected for
hemoglobin(DLCO) ≥ 50% and 40% of predicted respectively.
- Karnofsky performance status > 70.
- A negative pregnancy test will be required for all women of child bearing potential.
Breast feeding is not permitted.
- No HIV infection. Patients with immune dysfunction are at a significantly higher risk
of toxicities from intensive immunosuppressive therapies.
- No evidence of active bacterial, viral or fungal infection at the time of transplant
- No active alcohol or substance abuse within 6 months of study entry.
- Prior allogeneic transplant is acceptable.
- No history of intolerance or allergic reactions with atorvastatin or other statins.
- Patients who have previously been taking atorvastatin or any other statin will be
eligible as long as there is no contraindication to switch to atorvastatin 40mg/day
in the opinion of the treating physician.
- Patients undergoing a T-cell depleted allogeneic transplantation will not be
- Patients receiving another investigational drug are not eligible unless cleared by
Principal Investigator. Patients with prior malignancies except resected basal cell
carcinoma, treated carcinoma in-situ, or other hematologic diseases for which
allogeneic HSCT is a treatment strategy, are not eligible. Cancer treated with
curative intent < 5 years previously will not be allowed unless approved by the