Atorvastatin as GVHD Prophylaxis for Allogeneic Hematopoietic Cell Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Medical College of Wisconsin
Sponsor:
Collaborator:
West Virginia University
Information provided by (Responsible Party):
Mehdi Hamadani, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01665677
First received: August 13, 2012
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

Hematopoietic stem cell transplantation is a procedure in which a person receives blood forming stem cells from a person called a "donor". The stem cells can be obtained from the hollow part of the hip bone or from blood.

A serious problem with this treatment is Graft Versus Host Disease (GVHD). This happens when stem cells from the donor attack normal cells of the recipient. Currently, there is no universal standard of care in the United STates to prevent GVHD.

This study is being done to see if a medicine that is used to lower cholesterol can also help in reducing GVHD.

Patients will receive atorvastatin daily by mouth starting 14 days before stem cell transplant. They will continue to take atorvastatin until 180 days after transplant. This medicine may be stopped earlier if there is a bad side effect or a severe GVHD. Patients will also receive standard treatment to prevent GVHD. Patients will undergo many tests that are standard for their treatment at West Virginia University (WVU), including blood tests to check blood counts, kidney function and HIV status; blood test to check for pregnancy; Multi Gated Acquisition Scan (MUGA scan)or echocardiogram to test heart function; lung function testing; and bone marrow aspirate or biopsy. Patients will also have the option to provide blood samples for optional research related to the study.


Condition Intervention Phase
Graft vs Host Disease
Drug: Atorvastatin calcium
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 of Atorvastatin, Micro-dose Methotrexate and Tacrolimus Administered Only to Transplant Recipients for the Prophylaxis of Acute Graft-versus-host Disease Following Allogeneic Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Medical College of Wisconsin:

Primary Outcome Measures:
  • Determine efficacy of atorvastatin/tacrolimus/methotrexate in preventing GVHD [ Time Frame: One year ] [ Designated as safety issue: Yes ]
    Determine the efficacy of an atorvastatin/tacrolimus/methotrexate regimen in preventing grade II-IV acute GVHD in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT)

  • Assess the safety of an atorvastatin/tacrolimus methotrexate regimen in patients undergoing allogeneic HSCT [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Assess the safety of an atorvastatin/tacrolimus methotrexate regimen in patients undergoing allogeneic HSCT


Secondary Outcome Measures:
  • To assess rates of chronic GVHD [ Time Frame: One year ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Atorvastatin calcium (Lipitor)

Atorvastatin will be administered at a dose of 40 mg 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 until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.

Drug: Atorvastatin calcium
40 mg PO daily
Other Name: Lipitor
Experimental: Unrelated Donor

Atorvastatin will be administered at a dose of 40 mg 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 until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.

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

Detailed Description:

Acute graft-versus-host disease (GVHD) is one of the most frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT) (1). It develops in 30-75% of recipients of allogeneic HSCT depending on the degree of histocompatibility between the donor and the recipient, number of T-cells in the graft, recipient's age and GVHD prophylactic regimen used (2-4). Novel strategies designed to effectively prevent the development of this life threatening complication of allogeneic transplantation are urgently needed.

  Eligibility

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

Patient Eligibility Criteria:

  • Patients with a history of a hematological malignancy or bone marrow failure syndrome suitable for allogeneic stem cell transplantation in the opinion of treating transplant physician.
  • 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).
  • All patients must have at least one suitable human leukocyte antigen (HLA)-matched sibling or unrelated donor according to transplant center's guidelines (for selection of appropriate sibling donor).
  • Patient must provide informed consent.
  • Left ventricular ejection fraction ≥ 40%. No uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart failure.
  • Bilirubin ≤ 2 x the upper limit of normal (ULN) and aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 3 x ULN; and absence of hepatic cirrhosis. For patients with Gilbert's syndrome, bilirubin ≤ 3 x ULN is permitted.
  • Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation.
  • DLCOcor (carbon monoxide diffusing capacity; corrected for hemoglobin) or forced expiratory volume at one second (FEV1) or DL/VA ≥ 40% of predicted (a pulmonary function test).
  • Karnofsky performance status > 70.
  • A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
  • Patients with positive HIV serology are eligible.
  • No evidence of active bacterial, viral or fungal infection at the time of transplant conditioning.
  • Patients with history of intolerance or allergic reactions with atorvastatin will not be eligible.
  • 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.
  • Patients undergoing a T-cell depleted allogeneic transplantation will not be eligible.
  • Patients receiving conditioning regimens containing antithymocyte globulin, and/or campath will not be eligible.
  • 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 Granulocyte colony-stimulating factor(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.
  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: NCT01665677

Locations
United States, West Virginia
West Virginia University Hospitals Mary Babb Randolph Cancer Center Recruiting
Morgantown, West Virginia, United States, 26506
Contact: Pam Bunner, MT    304-598-4511    bunnerp@wvuhealthcare.com   
Contact: Crystal Street, MT    304-598-4512    streetc@wvuhealthcare.com   
Principal Investigator: Michael Craig, MD         
Sub-Investigator: William Tse, MD         
Sub-Investigator: Soumit Basu, MD, PhD         
Sub-Investigator: Laura Gibson, PhD         
Sub-Investigator: Jame Abraham, MD         
Sub-Investigator: William Petros, PharmD         
Sub-Investigator: Aaron Cumpston, PharmD         
Sub-Investigator: Scot C Remick, MD         
Sub-Investigator: Jeffrey Vos, MD         
Sub-Investigator: Abraham Kanate, MD         
United States, Wisconsin
Froedtert Hospital and the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Cancer Center Clinical Trials Office    866-680-0505 ext 8900    cccto@mcw.edu   
Contact: Cancer Center Clinical Trials Office    414-805-8900    cccto@mcw.edu   
Principal Investigator: Mehdi Hamadani, MD         
Sponsors and Collaborators
Mehdi Hamadani
West Virginia University
Investigators
Principal Investigator: Michael Craig, MD West Virginia University
Principal Investigator: Mehdi Hamadani, MD Medical College of Wisconsin
  More Information

Publications:
Responsible Party: Mehdi Hamadani, Associate Professor (Principal Investigator), Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01665677     History of Changes
Other Study ID Numbers: PRO00021090, WVU 011012
Study First Received: August 13, 2012
Last Updated: April 2, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Medical College of Wisconsin:
Graft vs Host Disease
GVHD
Allogeneic hematopoietic stem cell transplantation
HSCT
Atorvastatin

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 October 22, 2014