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

This study has been completed.
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Marco Mielcarek, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01525407
First received: January 31, 2012
Last updated: July 18, 2017
Last verified: July 2017
  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 Procedure: Allogeneic Hematopoietic Stem Cell Transplantation Drug: Atorvastatin Calcium Procedure: Peripheral Blood Stem Cell Transplantation Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (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 Marco Mielcarek, Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Grade 3-4 Acute GVHD [ Time Frame: First 100 days after transplant ]
    Cumulative incidence rate of grade 3-4 acute GVHD with death as a completing risk, assessed at day 100 in the patients/recipients.


Secondary Outcome Measures:
  • Chronic Extensive GVHD [ Time Frame: 2 years post transplant ]
    Cumulative incidence rate of chronic extensive GVHD with death as a competing risk, assessed at 2 years in the patients/recipients.

  • Disease-free Survival [ Time Frame: 1 year after transplant ]
    Evaluated as Kaplan-Meier estimate in the patients/recipients.

  • Grades II-IV Acute GVHD [ Time Frame: First 100 days after transplant ]
    Cumulative incidence rate of grades II-IV acute GVHD with death as a competing risk, assessed at 100 days in the patients/recipients.

  • Non-relapse Mortality [ Time Frame: At day 100 ]
    Cumulative incidence rate of non-relapse mortalities, assessed at day 100 in the patients/recipients.

  • Non-relapse Mortality [ Time Frame: At 1 year after HCT ]
    Cumulative incidence rate of non-relapse mortalities, assessed at one year in the patients/recipients.

  • Overall Survival [ Time Frame: 1 year after transplant ]
    Determined and presented as Kaplan-Meier estimates, assessed at 1 year in the patients/recipients.

  • Proportion of Donors Who Have to Discontinue Atorvastatin Because of Toxicity [ Time Frame: Until completion of stem cell collection (on average 14 days) ]
  • Proportion of Patients Requiring Secondary Systemic Immunosuppressive Therapy [ Time Frame: First 100 days after transplant ]
  • Recurrent or Progressive Malignancy [ Time Frame: Up to 3 years ]
    Cumulative incidence rate of recurrent or progressive malignancy with death as a competing risk, assessed at 3 years in the patients/recipients.


Enrollment: 83
Study Start Date: May 2012
Study Completion Date: February 2016
Primary Completion Date: September 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.
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo myeloablative allogeneic PBSC transplant
Other Names:
  • allogeneic stem cell transplantation
  • HSC
  • HSCT
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
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplantation

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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
  • DONOR: Total creatinine kinase > 2 times the ULN
  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
Stanford, California, United States, 94305
United States, Colorado
Colorado Blood Cancer Institute
Denver, Colorado, United States, 80907
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Marco Mielcarek Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Responsible Party: Marco Mielcarek, Principal Investigator, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01525407     History of Changes
Other Study ID Numbers: 2545.00
NCI-2011-03827 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2545.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium )
P30CA015704 ( U.S. NIH Grant/Contract )
R01HL108307 ( U.S. NIH Grant/Contract )
Study First Received: January 31, 2012
Results First Received: April 11, 2017
Last Updated: July 18, 2017

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

ClinicalTrials.gov processed this record on September 21, 2017