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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Malignant Neoplasm

Intervention / Treatment
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* Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
* Drug: Atorvastatin Calcium
* Procedure: Peripheral Blood Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Supportive care (donor statin treatment)<br>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<br>* Undergo myeloablative allogeneic PBSC transplant<br>* Other names: HSCT;Drug: Atorvastatin Calcium<br>* Given PO<br>* Other names: Lipitor;Procedure: Peripheral Blood Stem Cell Transplantation<br>* Undergo myeloablative allogeneic PBSC transplant<br>* Other names: Peripheral Stem Cell Transplantation;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chronic Extensive GVHD | Cumulative incidence rate of chronic extensive GVHD with death as a competing risk, assessed at 2 years in the patients/recipients. | 2 years post transplant | 
| Disease-free Survival | Evaluated as Kaplan-Meier estimate in the patients/recipients. | 1 year after transplant | 
| Grades II-IV Acute GVHD | Cumulative incidence rate of grades II-IV acute GVHD with death as a competing risk, assessed at 100 days in the patients/recipients. | First 100 days after transplant | 
| Non-relapse Mortality | Cumulative incidence rate of non-relapse mortalities, assessed at day 100 in the patients/recipients. | At day 100 | 
| Non-relapse Mortality | Cumulative incidence rate of non-relapse mortalities, assessed at one year in the patients/recipients. | At 1 year after HCT | 
| Overall Survival | Determined and presented as Kaplan-Meier estimates, assessed at 1 year in the patients/recipients. | 1 year after transplant | 
| Proportion of Donors Who Have to Discontinue Atorvastatin Because of Toxicity |  | Until completion of stem cell collection (on average 14 days) | 
| Proportion of Patients Requiring Secondary Systemic Immunosuppressive Therapy |  | First 100 days after transplant | 
| Recurrent or Progressive Malignancy | Cumulative incidence rate of recurrent or progressive malignancy with death as a competing risk, assessed at 3 years in the patients/recipients. | Up to 3 years |