Atorvastatin as GVHD Prophylaxis for Allogeneic Hematopoietic Cell Transplantation

This study is currently recruiting participants.
Verified April 2014 by Medical College of Wisconsin
Sponsor:
Collaborator:
West Virginia University
Information provided by (Responsible Party):
Mehdi Hamadani, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT01665677
First received: August 13, 2012
Last updated: April 2, 2014
Last verified: April 2014

August 13, 2012
April 2, 2014
September 2012
December 2015   (final data collection date for primary outcome measure)
  • Determine efficacy of atorvastatin/tacrolimus/methotrexate in preventing GVHD [ Time Frame: One year ] [ Designated as safety issue: Yes ]
    Determine the efficacy of an atorvastatin/tacrolimus/methotrexate regimen in preventing grade II-IV acute GVHD in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT)
  • Assess the safety of an atorvastatin/tacrolimus methotrexate regimen in patients undergoing allogeneic HSCT [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Assess the safety of an atorvastatin/tacrolimus methotrexate regimen in patients undergoing allogeneic HSCT
  • Determine efficacy of atorvastatin/tacrolimus/methotrexate in preventing GVHD [ Time Frame: One year ] [ Designated as safety issue: Yes ]
    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)
  • Assess the safety of an atorvastatin/tacrolimus methotrexate regimen in patients undergoing matched-sibling allogeneic HSCT [ Time Frame: 30 days ] [ Designated as safety issue: Yes ]
    Assess the safety of an atorvastatin/tacrolimus methotrexate regimen in patients undergoing matched-sibling allogeneic HSCT
Complete list of historical versions of study NCT01665677 on ClinicalTrials.gov Archive Site
To assess rates of chronic GVHD [ Time Frame: One year ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Atorvastatin as GVHD Prophylaxis for Allogeneic Hematopoietic Cell Transplantation
Phase II Study of Atorvastatin, Micro-dose Methotrexate and Tacrolimus Administered Only to Transplant Recipients for the Prophylaxis of Acute Graft-versus-host Disease Following Allogeneic Hematopoietic Cell Transplantation

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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Graft vs Host Disease
Drug: Atorvastatin calcium
40 mg PO daily
Other Name: Lipitor
  • Experimental: Atorvastatin calcium (Lipitor)

    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.

    Intervention: Drug: Atorvastatin calcium
  • Experimental: Unrelated Donor

    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.

    Intervention: Drug: Atorvastatin calcium

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
60
December 2015
December 2015   (final data collection date for primary outcome measure)

Patient Eligibility 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%. No uncontrolled arrhythmias or uncontrolled New York Heart Association class III-IV heart failure.
  • 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.
  • DLCOcor (carbon monoxide diffusing capacity; 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.
  • No evidence of active bacterial, viral or fungal infection at the time of transplant conditioning.
  • Patients with history of intolerance or allergic reactions with atorvastatin will not be 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.
  • Patients undergoing a T-cell depleted allogeneic transplantation will not be eligible.
  • Patients receiving conditioning regimens containing antithymocyte globulin, and/or campath will not be eligible.
  • 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.
Both
18 Years to 75 Years
No
Not Provided
United States
 
NCT01665677
PRO00021090, WVU 011012
Yes
Mehdi Hamadani, Medical College of Wisconsin
Mehdi Hamadani
West Virginia University
Principal Investigator: Michael Craig, MD West Virginia University
Principal Investigator: Mehdi Hamadani, MD Medical College of Wisconsin
Medical College of Wisconsin
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP