Atorvastatin as GVHD Prophylaxis for Allogeneic Hematopoietic Cell Transplantation

Mehdi Hamadani

Status and phase

Completed

Phase 2

Conditions

Graft vs Host Disease

Treatments

Drug: Atorvastatin calcium

Study type

Interventional

Funder types

Other

Identifiers

NCT01665677

PRO00021090

116837-IRG-09-061-01 (Other Grant/Funding Number)

WVU 011012 (Other Identifier)

Details and patient eligibility

About

Hematopoietic stem cell transplantation is a procedure in which a person receives blood forming stem cells from a person called a "donor." The stem cells can be obtained from the hollow part of the hip bone or from blood.

A serious problem with this treatment is graft-versus-host disease (GVHD). This happens when stem cells from the donor attack normal cells of the recipient. Currently, there is no universal standard of care in the United States to prevent GVHD.

This study is being done to see if a medicine that is used to lower cholesterol can also help in reducing GVHD.

Patients will receive atorvastatin daily by mouth starting 14 days before stem cell transplant. They will continue to take atorvastatin until 180 days after transplant. This medicine may be stopped earlier if there is a bad side effect or a severe GVHD. Patients will also receive standard treatment to prevent GVHD. Patients will undergo many tests that are standard for their treatment at West Virginia University (WVU), including blood tests to check blood counts, kidney function and HIV status; blood test to check for pregnancy; Multi Gated Acquisition Scan (MUGA scan)or echocardiogram to test heart function; lung function testing; and bone marrow aspirate or biopsy. Patients will also have the option to provide blood samples for optional research related to the study.

Full description

Acute graft-versus-host disease (GVHD) is one of the most frequent complications after allogeneic hematopoietic stem cell transplantation (HSCT).(1) It develops in 30-75% of recipients of allogeneic HSCT depending on the degree of histocompatibility between the donor and the recipient, number of T-cells in the graft, recipient's age and GVHD prophylactic regimen used. (2-4) Novel strategies designed to effectively prevent the development of this life threatening complication of allogeneic transplantation are urgently needed.

Enrollment

69 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients with a history of a hematological malignancy or bone marrow failure syndrome suitable for allogeneic stem cell transplantation in the opinion of treating transplant physician.
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).
All patients must have at least one suitable human leukocyte antigen (HLA)-matched sibling or unrelated donor according to transplant center's guidelines (for selection of appropriate sibling donor).
Patient must provide informed consent.
Left ventricular ejection fraction ≥ 40%.
Bilirubin ≤ 2 x the upper limit of normal (ULN) and aspartate aminotransferase (AST), and alanine aminotransferase (ALT) ≤ 3 x ULN; and absence of hepatic cirrhosis. For patients with Gilbert's syndrome, bilirubin ≤ 3 x ULN is permitted.
Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation.
Carbon monoxide diffusing capacity (DLCOcor) corrected for hemoglobin or forced expiratory volume at one second (FEV1) or DL/VA ≥ 40% of predicted (a pulmonary function test).
Karnofsky performance status > 70.
A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
Patients with positive HIV serology are eligible.
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.
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 Granulocyte colony-stimulating factor(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.

Exclusion criteria

Uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart failure.
Evidence of active bacterial, viral or fungal infection at the time of transplant conditioning.
History of intolerance or allergic reactions with atorvastatin will not be eligible.
Undergoing a T-cell depleted allogeneic transplantation
Receiving conditioning regimens containing anti-thymocyte globulin, and/or campath

Trial design

Primary purpose

Prevention

Allocation

Non-Randomized

Interventional model

Single Group Assignment

Masking

None (Open label)

69 participants in 2 patient groups

Atorvastatin calcium (Lipitor)

Experimental group

Description:

Atorvastatin will be administered at a dose of 40 mg 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 until the patient develops grade II-IV acute GVHD, extensive chronic GVHD, or any grade 3-4 toxicity related to atorvastatin.

Treatment:

Drug: Atorvastatin calcium

Unrelated Donor

Experimental group

Description:

Treatment:

Drug: Atorvastatin calcium

Trial documents