Atorvastatin for the Prophylaxis of Acute Graft-versus-host Disease in Patients Undergoing Matched Sibling Allogeneic Transplantation

Graft vs Host Disease Clinical Trial

Official title:

Phase II Study Evaluating the Safety and Efficacy of Atorvastatin for the Prophylaxis of Acute Graft-versus-host Disease in Patients Undergoing Matched Sibling Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01175148
• Other study ID #: WVU11010
• Status: Active, not recruiting
• Phase: Phase 2
• First received: August 2, 2010
• Last updated: January 11, 2013
• Start date: July 2010
• Est. completion date: December 2014

Study information

• Verified date: January 2013
• Source: West Virginia University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Atorvastatin for prevention of acute GVHD

Description:

This is a phase II study of atorvastatin for the prophylaxis of acute GVHD in patients undergoing matched-sibling allogeneic HSCT. This study will explore a two-pronged acute GVHD prophylaxis strategy, consisting of pre-treating consenting sibling donors with atorvastatin before stem cell collection, followed by the addition of atorvastatin to methotrexate/tacrolimus-based GVHD prophylaxis.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Graft vs Host Disease

Intervention

Drug:
• Atorvastatin calcium (Lipitor)
40 mg PO daily

Locations

Country	Name	City	State
United States	West Virginia University Hospitals Mary Babb Randolph Cancer Center	Morgantown	West Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Mehdi Hamadani

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

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. Epub 2007 Sep 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Determine the efficacy of an atorvastatin/tacrolimus/methotrexate regimen in preventing grade II-IV acute GVHD in patients undergoing matched-sibling allogeneic hematopoietic stem cell transplantation (HSCT)		100 days	No
Primary	Assess the safety of an atorvastatin/tacrolimus/methotrexate regimen in patients undergoing matched-sibling allogeneic HSCT.		One year	Yes
Primary	Assess the safety of an atorvastatin in sibling HSCT donors.		30 days	Yes
Secondary	To assess rates of chronic GVHD.		One year	No
Secondary	To assess non-relapse mortality at 100 days post-HSCT.		100 days post-HSCT	Yes