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

Malignant Neoplasm Clinical Trial

Official title:

Donor Statin Treatment for Prevention of Severe Acute GVHD After Myeloablative Hematopoietic Cell Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01525407
• Other study ID #: 2545.00
• Secondary ID: NCI-2011-0382725
• Status: Completed
• Phase: Phase 2
• First received: January 31, 2012
• Last updated: February 26, 2016
• Start date: May 2012

Study information

• Verified date: November 2015
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Malignant Neoplasm
• Neoplasms

Intervention

Procedure:
• Allogeneic Hematopoietic Stem Cell Transplantation
Undergo myeloablative allogeneic PBSC transplant

Drug:
• Atorvastatin Calcium
Given PO

Procedure:
• Peripheral Blood Stem Cell Transplantation
Undergo myeloablative allogeneic PBSC transplant

Locations

Country	Name	City	State
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington
United States	Stanford University Hospitals and Clinics	Stanford	California

Sponsors (3)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Grade 3-4 acute GVHD	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.	First 100 days after transplant	No
Secondary	Chronic extensive GVHD	Will be assessed with the use of cumulative incidence plots. Will be assessed with the use of cumulative incidence plots.	Up to 3 years after transplant	No
Secondary	Disease-free survival	Evaluated as Kaplan-Meier estimate.	1 year after transplant	No
Secondary	Grades II-IV acute GVHD	Will be assessed with the use of cumulative incidence plots.	First 100 days after transplant	No
Secondary	Grades II-IV chronic GVHD	Will be assessed with the use of cumulative incidence plots. Will be assessed with the use of cumulative incidence plots.	Up to 3 years after transplant	No
Secondary	Non-relapse mortality	Will be assessed with the use of cumulative incidence plots.	At day 100	No
Secondary	Non-relapse mortality	Will be assessed with the use of cumulative incidence plots.	At 1 year after HCT	No
Secondary	Overall survival	Determined and presented as Kaplan-Meier estimates.	1 year after transplant	No
Secondary	Proportion of donors who have to discontinue atorvastatin because of toxicity		Up to stem cell collection	No
Secondary	Proportion of patients requiring secondary systemic immunosuppressive therapy	Will be assessed with the use of cumulative incidence plots.	First 100 days after transplant	No
Secondary	Recurrent or progressive malignancy	Will be assessed with the use of cumulative incidence plots.	Up to 3 years	No