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

West Virginia University

Status and phase: Completed; Phase 2

Conditions: Graft vs Host Disease

Treatments: Drug: Atorvastatin calcium (Lipitor)

Study type: Interventional

Funder types: Other

Identifiers

NCT01175148

WVU11010

Details and patient eligibility

About

Atorvastatin for prevention of acute GVHD

Full 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.

Enrollment: 60 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Recipient - Atorvastatin to prevent GVHD

Experimental group

Description:

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.

Treatment:

Drug: Atorvastatin calcium (Lipitor)

Donor - Atorvastatin conditioning for donors

Other group

Description:

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.

Treatment:

Drug: Atorvastatin calcium (Lipitor)