Safety & Efficacy of Atorvastatin for Prophylaxis of Acute Graft Versus Host Disease in Patients With Hematological Malignancies HLA- Donor Hematopoietic Stem Cell Transplantation
Condition: Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Hematologic Neoplasms; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Graft vs Host Disease
Intervention: atorvastatin; Tacrolimus; methotrexate
Intervention description: donors-will receive atorvastatin 40 mg/day orally at least 14 days before anticipated first day of stem cell leukapheresis (LP) until successful completion of leukapheresis according to institutional guidelines.
Patients-will receive atorvastatin 40 mg starting at least 7 days before initiation of transplant conditioning regimen, to permit a 1 week observation period to rule out any atorvastatin-induced side effects before initiation of transplant conditioning. Patients will continue on atorvastatin with standard GVHD prophylaxis with tacrolimus and methotrexate until end of GVHD prophylaxis according to institutional standard guidelines, or until development of endpoint, which ever should occur first.; beginning on Day -2 through approximately Day +180 (that is, approximately 6 months after Day 0); Day +1, +3, and +6 and +11
Intervention MeSH terms: Methotrexate; Atorvastatin; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Leukemia; AML; ALL; MDS

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).
    

Eligibility 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.