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

NCT03066466 | Withdrawn Phase 3 DMC FDA Drug

• 1 other identifier: 208106
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome

Keywords

Acute Myeloid Leukemia; Acute Lymphocytic Leukemia; Myelodysplastic Syndrome; BMT; Matched unrelated donor transplant; Graft versus Host Disease; GVHD

Outcome Measures

Primary Outcomes (1)

• The primary objective is to determine the cumulative incidence of chronic GVHD at one year after stem cell transplantation and treatment with atorvastatin

  National Institutes of Health Chronic Graft-Versus-Host Disease Grading and Form

  2 years

Secondary Outcomes (7)

• To determine the cumulative incidence of grade 3 to 4 acute GVHD

  100 days

• To determine rate of disease relapse

  2 years

• To determine non-relapse mortality (NRM)

  2 years

• To determine progression-free survival (PFS)

  2 years

• To determine overall survival (OS)

  2 years

Other Outcomes (1)

• To determine the effect of atorvastatin on immune reconstitution

  2 years

Study Arms (2)

Arm A: Atorvastatin

EXPERIMENTAL

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; Drug: Methotrexate; Drug: Tacrolimus

Arm B: Standard of Care

ACTIVE COMPARATOR

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; Drug: Tacrolimus

Interventions

Atorvastatin DRUG

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

Also known as: Lipitor

Arm A: Atorvastatin

Methotrexate DRUG

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

Also known as: Trexall

Arm A: Atorvastatin; Arm B: Standard of Care

Tacrolimus DRUG

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

Also known as: Prograft

Arm A: Atorvastatin; Arm B: Standard of Care

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Loyola University: lead

Study Sites (1)

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Graft vs Host Disease

Interventions

Atorvastatin; Methotrexate; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Macrolides; Lactones; Organic Chemicals

Study Officials

• Patrick Stiff, MD

  Cardinal Bernardin Cancer Center, Loyola University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, two arms

Study Record Dates

• First Submitted: February 23, 2017
• First Posted: February 28, 2017
• Study Start: December 10, 2019
• Primary Completion: February 28, 2020
• Study Completion: February 28, 2021
• Last Updated: April 27, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)