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

Phase 2

Completed

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

Brief 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.

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.

Recruitment & 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

Arm && Interventions

Group	Intervention	Description
Supportive care (donor statin treatment)	Allogeneic Hematopoietic Stem Cell Transplantation	Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection.
Supportive care (donor statin treatment)	Peripheral Blood Stem Cell Transplantation	Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection.
Supportive care (donor statin treatment)	Atorvastatin Calcium	Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection.

Primary Outcome Measures

Name	Time	Method
Grade 3-4 Acute GVHD	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

Name	Time	Method
Chronic Extensive GVHD	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.
Proportion of Donors Who Have to Discontinue Atorvastatin Because of Toxicity	Until completion of stem cell collection (on average 14 days)
Grades II-IV Acute GVHD	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.
Recurrent or Progressive Malignancy	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.
Disease-free Survival	1 year after transplant	Evaluated as Kaplan-Meier estimate in the patients/recipients.
Overall Survival	1 year after transplant	Determined and presented as Kaplan-Meier estimates, assessed at 1 year in the patients/recipients.
Non-relapse Mortality	At 1 year after HCT	Cumulative incidence rate of non-relapse mortalities, assessed at one year in the patients/recipients.
Proportion of Patients Requiring Secondary Systemic Immunosuppressive Therapy	First 100 days after transplant

Locations (3): Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
🇺🇸
Seattle, Washington, United States
Stanford University Hospitals and Clinics
🇺🇸
Stanford, California, United States
Colorado Blood Cancer Institute
🇺🇸
Denver, Colorado, United States