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Trial record 41 of 325 for:    "Acute Lymphocytic Leukemia" | "Methotrexate"

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

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ClinicalTrials.gov Identifier: NCT03066466
Recruitment Status : Recruiting
First Posted : February 28, 2017
Last Update Posted : March 11, 2019
Sponsor:
Information provided by (Responsible Party):
Patrick Stiff, Loyola University

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 207 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, 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
Estimated Study Start Date : December 10, 2019
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : February 28, 2021


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 Name: Lipitor

Drug: Methotrexate
IV medication given to prevent graft versus host disease in bone marrow transplant.
Other Name: Trexall

Drug: Tacrolimus
IV or Oral medication given to prevent graft versus host disease in bone marrow transplant.
Other Name: 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 Name: Trexall

Drug: Tacrolimus
IV or Oral medication given to prevent graft versus host disease in bone marrow transplant.
Other Name: Prograft




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


Secondary Outcome Measures :
  1. To determine the cumulative incidence of grade 3 to 4 acute GVHD [ Time Frame: 100 days ]
    National Institutes of Health Acute Graft-Versus-Host Disease Grading and Form

  2. To determine rate of disease relapse [ Time Frame: 2 years ]
    Blood work and/or bone marrow biopsy will be used

  3. To determine non-relapse mortality (NRM) [ Time Frame: 2 years ]
    Blood work and/or bone marrow biopsy will be used

  4. To determine progression-free survival (PFS) [ Time Frame: 2 years ]
    Blood work and/or bone marrow biopsy will be used

  5. To determine overall survival (OS) [ Time Frame: 2 years ]
    Blood work and/or bone marrow biopsy will be used

  6. Number of participants with Grade 4 through 5 Adverse Events that are related to study treatment, grading according to NCI CTCAE Version 4 [ Time Frame: 30 days of the last dose of protocol treatment ]
    Toxicities that are possibly, probably, and definitely related

  7. Determine the frequency and severity of chronic GVHD [ Time Frame: 2 years ]
    National Institutes of Health Chronic Graft-Versus-Host Disease Grading and Form


Other Outcome Measures:
  1. To determine the effect of atorvastatin on immune reconstitution [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03066466


Contacts
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Contact: Patrick Stiff, MD 708-327-3148 pstiff@lumc.edu
Contact: Mary Lee, RN 708-327-2241 mlee@luc.edu

Locations
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United States, Illinois
Loyola University Medical Center Recruiting
Maywood, Illinois, United States, 60153
Contact: Patrick Stiff, MD    708-327-3148    pstiff@lumc.edu   
Contact: Mary Lee, RN    708-327-2241    mlee@luc.edu   
Sponsors and Collaborators
Loyola University
Investigators
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Study Director: Patrick Stiff, MD Cardinal Bernardin Cancer Center, Loyola University

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Responsible Party: Patrick Stiff, Professor, Loyola University
ClinicalTrials.gov Identifier: NCT03066466     History of Changes
Other Study ID Numbers: 208106
First Posted: February 28, 2017    Key Record Dates
Last Update Posted: March 11, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Patrick Stiff, Loyola University:
Acute Myeloid Leukemia
Acute Lymphocytic Leukemia
Myelodysplastic Syndrome
BMT
Matched unrelated donor transplant
Graft versus Host Disease
GVHD
Additional relevant MeSH terms:
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Precursor Cell Lymphoblastic Leukemia-Lymphoma
Methotrexate
Leukemia
Leukemia, Myeloid, Acute
Preleukemia
Leukemia, Lymphoid
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Atorvastatin
Tacrolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists