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

NCT ID: NCT03066466

Last Updated: 2021-04-27

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-10
• Study Completion Date: 2021-02-28

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.

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.

Conditions

Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Atorvastatin

Intervention Type: DRUG

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

Methotrexate

Intervention Type: DRUG

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

Tacrolimus

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Methotrexate

Intervention Type: DRUG

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

Tacrolimus

Intervention Type: DRUG

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

Interventions

Atorvastatin

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

Intervention Type: DRUG

Methotrexate

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

Intervention Type: DRUG

Tacrolimus

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

Intervention Type: DRUG

Other Intervention Names

Lipitor; Trexall; Prograft

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Loyola University

OTHER

Sponsor Role: lead

Responsible Party

Patrick Stiff

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Patrick Stiff, MD

Role: STUDY_DIRECTOR

Cardinal Bernardin Cancer Center, Loyola University

Locations

Loyola University Medical Center

Maywood, Illinois, United States

Countries

United States

Other Identifiers

208106

Identifier Type: -

Identifier Source: org_study_id