Safety & Efficacy of Atorvastatin for Prophylaxis of Acute Graft Versus Host Disease in Patients With Hematological Malignancies HLA- Donor Hematopoietic Stem Cell Transplantation

The study is a single-arm phase II single institutional trial evaluating the safety and
efficacy of atorvastatin for the prophylaxis of acute GVHD in patients with hematological
malignancies undergoing HLA matched related donor HSCT. This study will explore a two-pronged
acute GVHD prophylaxis strategy, consisting of pre-treating consenting related donors with
atorvastatin before stem cell mobilization and collection, followed by atorvastatin plus
methotrexate/tacrolimus-based GVHD prophylaxis in transplant recipient patients.

Inclusion Criteria:

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
with atorvastatin.

- 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
fibrosis/cirrhosis.

- 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 consent.

- 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
conditioning.

- 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.

Exclusion Criteria:

- Patients undergoing a T-cell depleted allogeneic transplantation will not be eligible.

- 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
Principal Investigator.