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Atorvastatin for the Prophylaxis of Acute Graft-versus-host Disease in Patients Undergoing Matched Sibling Allogeneic Transplantation

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Mehdi Hamadani, West Virginia University
ClinicalTrials.gov Identifier:
NCT01175148
First received: August 2, 2010
Last updated: January 11, 2013
Last verified: January 2013
  Purpose

Atorvastatin for prevention of acute GVHD


Condition Intervention Phase
Graft vs Host Disease
Drug: Atorvastatin calcium (Lipitor)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Phase II Study Evaluating the Safety and Efficacy of Atorvastatin for the Prophylaxis of Acute Graft-versus-host Disease in Patients Undergoing Matched Sibling Hematopoietic Stem Cell Transplantation

Resource links provided by NLM:


Further study details as provided by West Virginia University:

Primary Outcome Measures:
  • Determine the efficacy of an atorvastatin/tacrolimus/methotrexate regimen in preventing grade II-IV acute GVHD in patients undergoing matched-sibling allogeneic hematopoietic stem cell transplantation (HSCT) [ Time Frame: 100 days ] [ Designated as safety issue: No ]
  • Assess the safety of an atorvastatin/tacrolimus/methotrexate regimen in patients undergoing matched-sibling allogeneic HSCT. [ Time Frame: One year ] [ Designated as safety issue: Yes ]
  • Assess the safety of an atorvastatin in sibling HSCT donors. [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess rates of chronic GVHD. [ Time Frame: One year ] [ Designated as safety issue: No ]
  • To assess non-relapse mortality at 100 days post-HSCT. [ Time Frame: 100 days post-HSCT ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: July 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Recipient-Donor Pair

Sibling donors will start taking atorvastatin orally at 40mg once daily between 14-28 days before the anticipated first day of apheresis or bone marrow harvest.

Atorvastatin will be administered at dose of 40mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning. Patients will receive atorvastatin until +180 days or development of grade 2 GVHD.

Drug: Atorvastatin calcium (Lipitor)
40 mg PO daily
Other Name: Lipitor

Detailed Description:

This is a phase II study of atorvastatin for the prophylaxis of acute GVHD in patients undergoing matched-sibling allogeneic HSCT. This study will explore a two-pronged acute GVHD prophylaxis strategy, consisting of pre-treating consenting sibling donors with atorvastatin before stem cell collection, followed by the addition of atorvastatin to methotrexate/tacrolimus-based GVHD prophylaxis.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DONOR ELIGIBILITY CRITERIA:

  1. Donors must be ≥18 years of age, and willing/able to provide informed consent.
  2. Female donors of child-bearing potential should have a negative pregnancy test, and must be not be breast feeding.
  3. Adequate hepatic function with bilirubin, AST and ALT < 2.5 x upper limit of normal.
  4. Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation.
  5. Adequate cardiac function as per institutional guidelines.
  6. Donors with positive HIV serologies are not eligible.
  7. No clinical evidence of uncontrolled active bacterial, viral or fungal infection at the time of stem cell mobilization.
  8. Donors must have a Karnofsky performance score of ≥60.
  9. Donors with history of intolerance or allergic reactions with atorvastatin will not be eligible. Hypersensitivity to any component of atorvastatin.
  10. Method of stem-cell collection from the sibling donor will be at the discretion of the treating physician. Although it is anticipated that majority of sibling donors will undergo G-CSF induced stem cell mobilization; however donors undergoing bone marrow harvest or stem cell mobilization with experimental agents (e.g. plerixafor) will remain eligible for the study.

PATIENT ELIGIBILITY CRITERIA:

  1. Patients with a history of a hematological malignancy or bone marrow failure syndrome suitable for matched sibling allogeneic stem cell transplantation in the opinion of treating transplant physician.
  2. Patients aged 18-75 years of age are eligible. Patients with age > 18 and ≤ 50 years will be eligible for myeloablative conditioning (MAC), while patients > 50 years of age, or those with previous history of autologous transplantation, high hematopoietic cell transplant comorbidity index (HCT-CI) score (>2), and baseline diagnosis of hodgkin's lymphoma, chronic lymphocytic leukemia and follicular lymphoma will be suitable for reduced intensity conditioning (RIC) transplantation (however intensity of conditioning regimen will remain at the discretion of treating physician).
  3. All patients must have at least one suitable HLA-matched sibling donor according to transplant center's guidelines (for selection of appropriate sibling donor).
  4. Patient must provide informed consent.
  5. Left ventricular ejection fraction > 40%. No uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart failure.
  6. Bilirubin <2mg/dl and AST and ALT < 3 x normal; and absence of hepatic cirrhosis.
  7. Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation.
  8. DLCO (diffusion capacity; corrected for hemoglobin) ≥ 50% of predicted.
  9. Karnofsky performance status > 70.
  10. A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
  11. Patients with positive HIV serology are not eligible.
  12. No evidence of active uncontrolled bacterial, viral or fungal infection at the time of transplant conditioning.
  13. Patients with history of intolerance or allergic reactions with atorvastatin will not be eligible.
  14. Patients who have previously been taking atorvastatin or any other statin drug will be eligible as long as there is no contraindication to switch to atorvastatin (40mg/day) in the opinion of the treating physician.
  15. Patients undergoing a T-cell depleted allogeneic transplantation will not be eligible.
  16. Patients receiving conditioning regimens containing antithymocyte globulin, and/or campath will not be eligible.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01175148

Locations
United States, West Virginia
West Virginia University Hospitals Mary Babb Randolph Cancer Center
Morgantown, West Virginia, United States, 26506
Sponsors and Collaborators
Mehdi Hamadani
Investigators
Principal Investigator: Mehdi Hamadani, MD West Virginia University
  More Information

Publications:
Responsible Party: Mehdi Hamadani, Assistant Professor, West Virginia University
ClinicalTrials.gov Identifier: NCT01175148     History of Changes
Other Study ID Numbers: WVU11010
Study First Received: August 2, 2010
Last Updated: January 11, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by West Virginia University:
HSCT
HPC
HCT
BMT
lipitor
atorvastatin
HMG-CoA Reductase Inhibitor
Hematopoietic stem cell transplant
allogeneic transplant
GVHD
graft-versus-host-disease
Graft vs Host Disease

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Atorvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014