Clinical trial NCT01525407: Donor Atorvastatin Treatment for Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Myeloablative Peripheral Blood Stem Cell Transplantation
Official title: Donor Statin Treatment for Prevention of Severe Acute GVHD After Myeloablative Hematopoietic Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Neoplasm
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-02-03
Enrollment: 83
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility 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

Primary outcomes:
measure: Grade 3-4 Acute GVHD
timeFrame: First 100 days after transplant
Secondary outcomes:
measure: Chronic Extensive GVHD
timeFrame: 2 years post transplant
measure: Disease-free Survival
timeFrame: 1 year after transplant
measure: Grades II-IV Acute GVHD
timeFrame: First 100 days after transplant
measure: Non-relapse Mortality
timeFrame: At day 100
measure: Non-relapse Mortality
timeFrame: At 1 year after HCT
measure: Overall Survival
timeFrame: 1 year after transplant
measure: Proportion of Donors Who Have to Discontinue Atorvastatin Because of Toxicity
timeFrame: Until completion of stem cell collection (on average 14 days)
measure: Proportion of Patients Requiring Secondary Systemic Immunosuppressive Therapy
timeFrame: First 100 days after transplant
measure: Recurrent or Progressive Malignancy
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University Hospitals and Clinics
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
name: Marco Mielcarek
role: PRINCIPAL_INVESTIGATOR
References: