Randomized Study: Standard of Care With or Without Atorvastatin for Prevention of GVHD for Matched Unrelated Donor BMT

Sponsor

Loyola University (Other)

Overall Status

Withdrawn

CT.gov ID

NCT03066466

Collaborator

(none)

Enrollment

Location

Arms

14.7

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Chronic Graft Versus Host Disease (GVHD) is one of the most challenging complications in long term survivors of allogeneic stem cell transplantation. As the number of allogeneic stem cell transplantations rises annually, the incidence of chronic GVHD rates have also increased due to a variety of factors including but not limited to increasing use of peripheral blood stem cell (PBSC) grafts, increasing age of both donors and recipients, and increased use of matched unrelated donors. One study showed much lower than traditional acute GHVD rate and chronic GHVD which is similar with historical rates when atorvastatin was administered prophylactically to both the donors as well as recipients of matched related allogeneic stem cell transplantation, lead to the interest in further examining the role of Atorvastatin in relation to the development of GVHD. The investigator hypothesize that the administration of atorvastatin in recipients of matched unrelated allogeneic stem cell transplantation, a group with known higher incidence of chronic GHVD, would be a safe and effective method to reduce the incidence of chronic GVHD. Matched related allogeneic stem cell transplantation recipients will not be included in this study due to their significantly lower GVHD rates. The definition and monitoring of our primary endpoint of GVHD is well established in clinical trials in allogeneic stem cell transplantations and the investiagor will utilize the National Institutes of Health (NIH) Staging System for the diagnosis and severity assessment of chronic GVHD as well the recommendations from the NIH Consensus Conference for the conduct of clinical trials in chronic GVHD.

Several secondary endpoints will be examined as defined below and include standard complementary data in the examination of clinical trials in chronic GVHD again as laid out by the NIH Consensus Conference for conduct of clinical trials in chronic GHVD.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia Acute Lymphocytic Leukemia Myelodysplastic Syndrome	Drug: Atorvastatin Drug: Methotrexate Drug: Tacrolimus	Phase 3

Detailed Description

This is a randomized, open label phase III trial in patients with Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, and Myelodysplastic Syndrome undergoing matched unrelated donor transplant.

Patients randomized to the treatment arm (atorvastatin):

The prophylaxis atorvastatin treatment (taken by mouth) for GVHD will start at 14 days prior to transplant and continue until 365 days post-transplant or until development of significant adverse events or desire of the primary treating physician to stop the administration.

The patients will also receive our institution's standard graft versus host disease prophylactic regimen which consists of two drugs. It has been shown that immunosuppression with two drugs is better than a single agent thus our institution utilizes a combination of Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate will be administered intravenously (IV) post-transplant on Days 1, 3 and 6. Tacrolimus will be administered 2 days prior to transplant and continue approximately 180 days post-transplant. Tacrolimus will be administered IV until patient can take it by mouth.

Patients randomized to standard of care:

Patients will receive our institution's standard graft versus host disease prophylactic regimen which consists of two drugs. It has been shown that immunosuppression with two drugs is better than a single agent thus our institution utilizes a combination of Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate will be administered intravenously (IV) post-transplant on Days 1, 3 and 6. Tacrolimus will be administered 2 days prior to transplant and continue approximately 180 days post-transplant. Tacrolimus will be administered IV until patient can take it by mouth.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, two armsRandomized, two arms

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Randomized Study of Atorvastatin Prophylaxis as a Supplement to Standard of Care Prophylaxis to Prevent Chronic Graft Versus Host Disease Allogeneic Stem Cell Transplantation From Matched Unrelated Donors

Anticipated Study Start Date :

Dec 10, 2019

Anticipated Primary Completion Date :

Feb 28, 2020

Anticipated Study Completion Date :

Feb 28, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A: Atorvastatin The preventative atorvastatin treatment 40mg daily by mouth for GVHD will start at 14 days prior to transplant & continue until 365 days post-transplant or if significant adverse events occur. Patients will also receive our standard of care for graft versus host disease prevention which consists of two drugs, Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate 5mg/metered square will be administered IV post-transplant on Days 1, 3 & 6. Tacrolimus will be administered 2 days prior to transplant & continue approximately 180 days post-transplant. Tacrolimus 0.03 mg/kg daily will be administered IV until patient can take it by mouth.	Drug: Atorvastatin Oral medication given to prevent graft versus host disease in bone marrow transplant. Other Names: Lipitor Drug: Methotrexate IV medication given to prevent graft versus host disease in bone marrow transplant. Other Names: Trexall Drug: Tacrolimus IV or Oral medication given to prevent graft versus host disease in bone marrow transplant. Other Names: Prograft
Active Comparator: Arm B: Standard of Care Patients will receive our standard of care for graft versus host disease prevention which consists of two drugs, Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate 5mg/metered square will be administered IV post-transplant on Days 1, 3 & 6. Tacrolimus will be administered 2 days prior to transplant & continue approximately 180 days post-transplant. Tacrolimus 0.03 mg/kg daily will be administered IV until patient can take it by mouth.	Drug: Methotrexate IV medication given to prevent graft versus host disease in bone marrow transplant. Other Names: Trexall Drug: Tacrolimus IV or Oral medication given to prevent graft versus host disease in bone marrow transplant. Other Names: Prograft

Arm

Intervention/Treatment

Experimental: Arm A: Atorvastatin

The preventative atorvastatin treatment 40mg daily by mouth for GVHD will start at 14 days prior to transplant & continue until 365 days post-transplant or if significant adverse events occur. Patients will also receive our standard of care for graft versus host disease prevention which consists of two drugs, Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate 5mg/metered square will be administered IV post-transplant on Days 1, 3 & 6. Tacrolimus will be administered 2 days prior to transplant & continue approximately 180 days post-transplant. Tacrolimus 0.03 mg/kg daily will be administered IV until patient can take it by mouth.

Drug: Atorvastatin

Oral medication given to prevent graft versus host disease in bone marrow transplant.

Other Names:

Lipitor

Drug: Methotrexate

IV medication given to prevent graft versus host disease in bone marrow transplant.

Other Names:

Trexall

Drug: Tacrolimus

IV or Oral medication given to prevent graft versus host disease in bone marrow transplant.

Other Names:

Prograft

Active Comparator: Arm B: Standard of Care

Patients will receive our standard of care for graft versus host disease prevention which consists of two drugs, Methotrexate and Tacrolimus. For all matched unrelated donor allogeneic transplantation patients, the following schedule of Methotrexate 5mg/metered square will be administered IV post-transplant on Days 1, 3 & 6. Tacrolimus will be administered 2 days prior to transplant & continue approximately 180 days post-transplant. Tacrolimus 0.03 mg/kg daily will be administered IV until patient can take it by mouth.

Drug: Methotrexate

IV medication given to prevent graft versus host disease in bone marrow transplant.

Other Names:

Trexall

Drug: Tacrolimus

IV or Oral medication given to prevent graft versus host disease in bone marrow transplant.

Other Names:

Prograft

Outcome Measures

Primary Outcome Measures

The primary objective is to determine the cumulative incidence of chronic GVHD at one year after stem cell transplantation and treatment with atorvastatin [2 years]
National Institutes of Health Chronic Graft-Versus-Host Disease Grading and Form

Secondary Outcome Measures

To determine the cumulative incidence of grade 3 to 4 acute GVHD [100 days]
National Institutes of Health Acute Graft-Versus-Host Disease Grading and Form
To determine rate of disease relapse [2 years]
Blood work and/or bone marrow biopsy will be used
To determine non-relapse mortality (NRM) [2 years]
Blood work and/or bone marrow biopsy will be used
To determine progression-free survival (PFS) [2 years]
Blood work and/or bone marrow biopsy will be used
To determine overall survival (OS) [2 years]
Blood work and/or bone marrow biopsy will be used
Number of participants with Grade 4 through 5 Adverse Events that are related to study treatment, grading according to NCI CTCAE Version 4 [30 days of the last dose of protocol treatment]
Toxicities that are possibly, probably, and definitely related
Determine the frequency and severity of chronic GVHD [2 years]
National Institutes of Health Chronic Graft-Versus-Host Disease Grading and Form

Other Outcome Measures

To determine the effect of atorvastatin on immune reconstitution [2 years]
Blood work will be used to evaluate recovery of white blood cells, red blood cells and platelets plus T and B cell count subset.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria

Men or women between 18-65 years of age
Patients designated to undergo allogeneic peripheral blood or bone marrow stem cell transplantation from matched unrelated donor following the diagnosis of one of the following primary diseases in early or intermediate disease status:
AML at the following stages at time of screening: 1st remission, 2nd remission, and 3rd or subsequent remission
ALL at the following stages at time of screening: 1st remission, 2nd remission, and 3rd or subsequent remission
MDS
Patients must have Performance Score (PS) greater than 70 percent

Exclusion Criteria

Cardiac: ejection fraction less than 40 percent or other significant cardiac disease
Pulmonary: FEV1 or DLCO less than 45 percent
Renal: creatinine greater than the upper limit of normal
Hepatic: bilirubin greater than 2.0 times the upper limit of normal
CNS: documented active CNS disease
Patients who are known to be positive for Hepatitis B surface antigen or Hepatitis C antibody, or who have tested positive for HIV