Donor Atorvastatin Treatment for Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Myeloablative Peripheral Blood Stem Cell Transplantation

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01525407
First received: January 31, 2012
Last updated: May 22, 2014
Last verified: May 2014
  Purpose

This phase II trial studies donor atorvastatin treatment for the prevention of severe acute graft-versus-host disease (GVHD) in patients undergoing myeloablative peripheral blood stem cell (PBSC) transplantation. Giving chemotherapy and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also prevent the patient's immune system reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving atorvastatin to the donor before transplant may prevent this from happening.


Condition Intervention Phase
Malignant Neoplasm
Drug: atorvastatin calcium
Procedure: peripheral blood stem cell transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Donor Statin Treatment for Prevention of Severe Acute GVHD After Myeloablative Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Grade 3-4 acute GVHD [ Time Frame: First 100 days after transplant ] [ Designated as safety issue: No ]
    A reduction in the cumulative incidence of acute GVHD from 15% to < 5% would represent a reasonable goal after hematopoietic cell transplant (HCT) with filgrastim (G-CSF)-mobilized blood cells and constitute study success.


Secondary Outcome Measures:
  • Grades II-IV acute GVHD [ Time Frame: First 100 days after transplant ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots.

  • Grades II-IV chronic GVHD [ Time Frame: Up to 3 years after transplant ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots. Will be assessed with the use of cumulative incidence plots.

  • Proportion of patients requiring secondary systemic immunosuppressive therapy [ Time Frame: First 100 days after transplant ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots.

  • Chronic extensive GVHD [ Time Frame: Up to 3 years after transplant ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots. Will be assessed with the use of cumulative incidence plots.

  • Recurrent or progressive malignancy [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots.

  • Non-relapse mortality [ Time Frame: At day 100 ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots.

  • Non-relapse mortality [ Time Frame: At 1 year after HCT ] [ Designated as safety issue: No ]
    Will be assessed with the use of cumulative incidence plots.

  • Disease-free survival [ Time Frame: 1 year after transplant ] [ Designated as safety issue: No ]
    Evaluated as Kaplan-Meier estimate.

  • Overall survival [ Time Frame: 1 year after transplant ] [ Designated as safety issue: No ]
    Determined and presented as Kaplan-Meier estimates.

  • Proportion of donors who have to discontinue atorvastatin because of toxicity [ Time Frame: Up to stem cell collection ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: May 2012
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Supportive care (donor statin treatment)
Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection.
Drug: atorvastatin calcium
Given PO
Other Names:
  • CI-981
  • Lipitor
Procedure: peripheral blood stem cell transplantation
Undergo myeloablative allogeneic PBSC transplant
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo myeloablative allogeneic PBSC transplant

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess whether 2 weeks of donor statin treatment reduces the risk of severe acute GVHD.

SECONDARY OBJECTIVES:

I. To assess whether 2 weeks of statin treatment of normal PBSC donors is feasible, tolerable and safe.

OUTLINE:

Donors receive atorvastatin orally (PO) beginning on day -14 and continuing until the last day of stem cell collection.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Human leukocyte antigen (HLA)-identical sibling donor
  • Myeloablative preparative regimen (i.e., >= TBI 12.0 Gy, >= busulfan (BU) 8.0 mg/kg PO, >= BU 6.4 mg/kg intravenously (IV), >= treosulfan 42 g/m^2 IV) according to investigational study or standard treatment plan; other "myeloablative" preparative regimens are acceptable as long as they are approved by the principal investigator or designee
  • Transplantation of PBSC
  • Cyclosporine (CSP)-based postgrafting immunosuppression
  • Willingness to give informed consent
  • DONOR: Age >= 18 years
  • DONOR: HLA genotypically identical sibling
  • DONOR: Willingness to give informed consent

Exclusion Criteria:

  • Nonmyeloablative preparative regimen
  • Participation in an investigational study that has acute GVHD as the primary endpoint
  • The allogeneic PBSC donor has a contraindication to statin treatment
  • DONOR: Age < 18 years
  • DONOR: Active liver disease (alanine aminotransferase [ALT] or aspartate aminotransferase [AST] levels > 2 times the upper limit of normal [ULN])
  • DONOR: History of myopathy
  • DONOR: Hypersensitivity to atorvastatin
  • DONOR: Pregnancy
  • DONOR: Nursing mother
  • DONOR: Current serious systemic illness
  • DONOR: Concurrent treatment with strong inhibitors of hepatic cytochrome P450 (CYP) 3A4 (i.e. clarithromycin, erythromycin, protease inhibitors, azole antifungals)
  • DONOR: Current use of statin drug
  • DONOR: Failure to meet Fred Hutchinson Cancer Research Center (FHCRC) or local criteria for stem cell donation
  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: NCT01525407

Locations
United States, California
Stanford University Hospitals and Clinics Not yet recruiting
Stanford, California, United States, 94305
Contact: Andrew Rezvani         
Principal Investigator: Andrew Rezvani         
United States, Colorado
Colorado Blood Cancer Institute Not yet recruiting
Denver, Colorado, United States, 80907
Contact: Juli Murphy    720-754-4890      
Principal Investigator: Richard A. Nash         
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Marco B. Mielcarek    206-667-2827      
Principal Investigator: Marco B. Mielcarek         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Marco Mielcarek Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01525407     History of Changes
Other Study ID Numbers: 2545.00, NCI-2011-03827, 2545.00, R01HL108307, P30CA015704
Study First Received: January 31, 2012
Last Updated: May 22, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Neoplasms
Atorvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on October 16, 2014