Atorvastatin for the Prophylaxis of Acute GVHD in Patients Undergoing Matched Sibling Allogeneic Transplantation

NCT01175148 | Completed Phase 2 Results DMC

• 1 other identifier: WVU11010
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Atorvastatin for prevention of acute GVHD

Conditions

Graft vs Host Disease

Keywords

HSCT; HPC; HCT; BMT; lipitor; atorvastatin; HMG-CoA Reductase Inhibitor; Hematopoietic stem cell transplant; allogeneic transplant; GVHD; graft-versus-host-disease; Graft vs Host Disease

Outcome Measures

Primary Outcomes (1)

• Cummalative Incidence of Grade 2 to 4 Acute Graft vs Host Diesease (GVHD) at Day 100 Post Transplant in HSCT Recipients

  Cummalative incidence of grade 2 to 4 acute Graft vs Host Diesease (GVHD) at day 100 post transplant will be will be histologically confirmed and graded in Hematopoietic Stem Cell Transplantation Recipients

  100 days post transplant

Study Arms (2)

Recipient - Atorvastatin to prevent GVHD

EXPERIMENTAL

Atorvastatin calcium (Lipitor) will be administered at dose of 40mg orally daily starting on day -14, to permit an approximately 1-week observation period to rule out any acute atorvastatin-induced side effects before the initiation of transplant conditioning. Patients will receive atorvastatin until +180 days or development of grade 2 GVHD. This is the experimental arm for outcome measures.

Drug: Atorvastatin calcium (Lipitor)

Donor - Atorvastatin conditioning for donors

OTHER

Sibling donors will start taking Atorvastatin calcium (Lipitor) orally at 40mg once daily between 14-28 days before the anticipated first day of apheresis or bone marrow harvest.

Drug: Atorvastatin calcium (Lipitor)

Interventions

Atorvastatin calcium (Lipitor) DRUG

40 mg PO daily

Also known as: Lipitor

Donor - Atorvastatin conditioning for donors; Recipient - Atorvastatin to prevent GVHD

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DONOR ELIGIBILITY CRITERIA: 1. Donors must be ≥18 years of age, and willing/able to provide informed consent. 2. Female donors of child-bearing potential should have a negative pregnancy test, and must be not be breast feeding. 3. Adequate hepatic function with bilirubin, AST and ALT \< 2.5 x upper limit of normal. 4. Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation. 5. Adequate cardiac function as per institutional guidelines. 6. Donors with positive HIV serologies are not eligible. 7. No clinical evidence of uncontrolled active bacterial, viral or fungal infection at the time of stem cell mobilization. 8. Donors must have a Karnofsky performance score of ≥60. 9. Donors with history of intolerance or allergic reactions with atorvastatin will not be eligible. Hypersensitivity to any component of atorvastatin. 10. Method of stem-cell collection from the sibling donor will be at the discretion of the treating physician. Although it is anticipated that majority of sibling donors will undergo G-CSF induced stem cell mobilization; however donors undergoing bone marrow harvest or stem cell mobilization with experimental agents (e.g. plerixafor) will remain eligible for the study. PATIENT ELIGIBILITY CRITERIA: 1. Patients with a history of a hematological malignancy or bone marrow failure syndrome suitable for matched sibling allogeneic stem cell transplantation in the opinion of treating transplant physician. 2. Patients aged 18-75 years of age are eligible. Patients with age \> 18 and ≤ 50 years will be eligible for myeloablative conditioning (MAC), while patients \> 50 years of age, or those with previous history of autologous transplantation, high hematopoietic cell transplant comorbidity index (HCT-CI) score (\>2), and baseline diagnosis of hodgkin's lymphoma, chronic lymphocytic leukemia and follicular lymphoma will be suitable for reduced intensity conditioning (RIC) transplantation (however intensity of conditioning regimen will remain at the discretion of treating physician). 3. All patients must have at least one suitable HLA-matched sibling donor according to transplant center's guidelines (for selection of appropriate sibling donor). 4. Patient must provide informed consent. 5. Left ventricular ejection fraction \> 40%. No uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart failure. 6. Bilirubin \<2mg/dl and AST and ALT \< 3 x normal; and absence of hepatic cirrhosis. 7. Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation. 8. DLCO (diffusion capacity; corrected for hemoglobin) ≥ 50% of predicted. 9. Karnofsky performance status \> 70. 10. A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted. 11. Patients with positive HIV serology are not eligible. 12. No evidence of active uncontrolled bacterial, viral or fungal infection at the time of transplant conditioning. 13. Patients with history of intolerance or allergic reactions with atorvastatin will not be eligible. 14. Patients who have previously been taking atorvastatin or any other statin drug will be eligible as long as there is no contraindication to switch to atorvastatin (40mg/day) in the opinion of the treating physician. 15. Patients undergoing a T-cell depleted allogeneic transplantation will not be eligible. 16. Patients receiving conditioning regimens containing antithymocyte globulin, and/or campath will not be eligible.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• West Virginia University: lead

Study Sites (1)

West Virginia University Hospitals Mary Babb Randolph Cancer Center

Morgantown, West Virginia, 26506, United States

Location

Related Publications (2)

• Hamadani M, Awan FT, Devine SM. The impact of HMG-CoA reductase inhibition on the incidence and severity of graft-versus-host disease in patients with acute leukemia undergoing allogeneic transplantation. Blood. 2008 Apr 1;111(7):3901-2. doi: 10.1182/blood-2008-01-132050. No abstract available.

  PMID: 18362217 BACKGROUND

• Zeiser R, Youssef S, Baker J, Kambham N, Steinman L, Negrin RS. Preemptive HMG-CoA reductase inhibition provides graft-versus-host disease protection by Th-2 polarization while sparing graft-versus-leukemia activity. Blood. 2007 Dec 15;110(13):4588-98. doi: 10.1182/blood-2007-08-106005. Epub 2007 Sep 7.

  PMID: 17827390 BACKGROUND

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Results Point of Contact

• Title: Pam Bunner, Clinical Research Specialist
• Organization: Mary Babb Randolph Cancer Center

bunnerp@wvuhealthcare.com

304-598-4511

Study Officials

• Mehdi Hamadani, MD

  West Virginia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 2, 2010
• First Posted: August 4, 2010
• Study Start: July 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 7, 2017
• Results First Posted: June 7, 2017

Record last verified: 2017-05

Locations

US (1)