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

• Status: Completed
• Trial end date: 2016-06-27
• Target enrollment: 0
• Participant gender: All

Summary

Phase II trial evaluating the safety & efficacy of Atorvastatin for prophylaxis of Acute Graft Versus Host Disease (GVHD) in patients with hematological malignances undergoing human leukocyte antigen (HLA)-Matched Related Donor Hematopoietic Stem Cell Transplant (HSCT).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Ohio State University Comprehensive Cancer Center
• Treatments: Atorvastatin; Atorvastatin Calcium; Methotrexate; Tacrolimus

Criteria

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.