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

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 2

Conditions: Malignant Neoplasm

Treatments: Drug: Atorvastatin Calcium; Procedure: Peripheral Blood Stem Cell Transplantation; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01525407

R01HL108307 (U.S. NIH Grant/Contract)

NCI-2011-03827 (Registry Identifier)

2545.00 (Other Identifier)

P30CA015704 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 83 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Supportive Care

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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83 participants in 1 patient group

Supportive care (donor statin treatment)

Experimental group

Description:

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

Treatment:

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation

Procedure: Peripheral Blood Stem Cell Transplantation

Drug: Atorvastatin Calcium