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

Information source: Ohio State University Comprehensive Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Acute Myelogenous Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome

Intervention: atorvastatin (Drug); Tacrolimus (Drug); methotrexate (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Ohio State University Comprehensive Cancer Center

Official(s) and/or principal investigator(s):
Yvonne Efebera, MD, Principal Investigator, Affiliation: Ohio State University

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).

Clinical Details

Official title: 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)

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Primary outcome: Efficacy of atorvastatin added to standard GVHD prophylaxis regimen with tacrolimus and methotrexate, in reducing the incidence of grade II-IV acute GVHD.

Secondary outcome:

Safety of atorvastatin in healthy sibling donors and transplant recipients in terms of adverse events and toxicities.

Neutrophil and platelet engraftment

chronic GVHD

NRM

Detailed description: 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.

Eligibility

Minimum age: 18 Years. Maximum age: 75 Years. Gender(s): Both.

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.

Locations and Contacts

Ohio State University, Columbus, Ohio 43210, United States
Additional Information

Jamesline

Starting date: December 2011
Last updated: March 31, 2015

Page last updated: August 23, 2015

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