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

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

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.

Study Overview

• Status: Completed
• Conditions: Malignant Neoplasm
• Intervention / Treatment: Drug: Atorvastatin Calcium; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Procedure: Peripheral Blood Stem Cell Transplantation

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.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Hospitals and Clinics
  • Colorado
    • Denver, Colorado, United States, 80907
      • Colorado Blood Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Supportive care (donor statin treatment); Donors receive atorvastatin calcium PO beginning on day -14 and continuing until the last day of stem cell collection.

Drug: Atorvastatin Calcium; Given PO; Other Names: Lipitor; CI-981; Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Undergo myeloablative allogeneic PBSC transplant; Other Names: HSC; HSCT; allogeneic stem cell transplantation; Procedure: Peripheral Blood Stem Cell Transplantation; Undergo myeloablative allogeneic PBSC transplant; Other Names: PBPC transplantation; Peripheral Blood Progenitor Cell Transplantation; Peripheral Stem Cell Support; Peripheral Stem Cell Transplantation

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fred Hutchinson Cancer Center
• Collaborators: National Cancer Institute (NCI); National Heart, Lung, and Blood Institute (NHLBI)

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): February 1, 2016

Study Registration Dates

• First Submitted: January 31, 2012
• First Submitted That Met QC Criteria: February 2, 2012
• First Posted (Estimate): February 3, 2012

Study Record Updates

• Last Update Posted (Actual): August 17, 2017
• Last Update Submitted That Met QC Criteria: July 18, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Calcium-Regulating Hormones and Agents; Atorvastatin; Calcium
• Other Study ID Numbers: 2545.00 (Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); NCI-2011-03827 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); R01HL108307 (U.S. NIH Grant/Contract)