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Trial record 1 of 1 for:    NCT01665677
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Atorvastatin as GVHD Prophylaxis for Allogeneic Hematopoietic Cell Transplantation

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ClinicalTrials.gov Identifier: NCT01665677
Recruitment Status : Completed
First Posted : August 15, 2012
Last Update Posted : September 16, 2021
Sponsor:
Collaborator:
West Virginia University
Information provided by (Responsible Party):
Mehdi Hamadani, Medical College of Wisconsin

Brief Summary:

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 or disease Intervention/treatment Phase
Graft vs Host Disease Drug: Atorvastatin calcium Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 75 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (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
Actual Study Start Date : January 20, 2014
Actual Primary Completion Date : July 9, 2021
Actual Study Completion Date : July 9, 2021


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Matched sibling transplants who develop grade II-IV acute GVHD. [ Time Frame: Up until Year 5 ]
    The number of subjects who develop grades II-IV acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets.

  2. Matched unrelated donors transplants who develop grade II-IV acute GVHD. [ Time Frame: Up until Year 5 ]
    The number of subjects who develop grade II-IV acute GVHD. Acute GVHD will be assessed by consensus criteria and graded on Bone Marrow Transplant Clinical Trials Network Manual of Procedures suggested grading sheets.


Secondary Outcome Measures :
  1. Matched sibling transplants who develop grade II-IV chronic GVHD. [ Time Frame: Up until Year 5 ]
    The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading will be according to National Institutes of Health (NIH) Criteria.

  2. Matched unrelated donors transplants who develop grade II-IV chronic GVHD. [ Time Frame: Up until Year 5 ]
    The number of subjects who develop grade II-IV chronic GVHD. Chronic GVHD diagnosis and grading will be according to NIH Criteria.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion 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%.
  • 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.
  • Carbon monoxide diffusing capacity (DLCOcor) 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.
  • 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.
  • 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.

Exclusion Criteria:

  • Uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart failure.
  • Evidence of active bacterial, viral or fungal infection at the time of transplant conditioning.
  • History of intolerance or allergic reactions with atorvastatin will not be eligible.
  • Undergoing a T-cell depleted allogeneic transplantation
  • Receiving conditioning regimens containing anti-thymocyte globulin, and/or campath

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01665677


Locations
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United States, West Virginia
West Virginia University Hospitals Mary Babb Randolph Cancer Center
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Mehdi Hamadani
West Virginia University
Investigators
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Principal Investigator: Michael Craig, MD West Virginia University
Principal Investigator: Mehdi Hamadani, MD Medical College of Wisconsin
Publications:
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Responsible Party: Mehdi Hamadani, Professor, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT01665677    
Other Study ID Numbers: PRO00021090
WVU 011012 ( Other Identifier: West Virginia )
First Posted: August 15, 2012    Key Record Dates
Last Update Posted: September 16, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Mehdi Hamadani, Medical College of Wisconsin:
Graft vs Host Disease
GVHD
Allogeneic hematopoietic stem cell transplantation
HSCT
Atorvastatin
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Atorvastatin
Calcium
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors