Acute Myeloid LeukemiaPhase 3NCT03066466
Randomized Study: Standard of Care With or Without Atorvastatin for Prevention of GVHD for Matched Unrelated Donor BMT
A Phase 3 study testing Atorvastatin, Methotrexate and Tacrolimus in people with Acute Myeloid Leukemia and Acute Lymphocytic Leukemia, run by Loyola University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplastic Syndrome
- What is being tested?
- Atorvastatin, Methotrexate and Tacrolimus
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Dec 2019to 28 Feb 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Loyola University Medical Center
Maywood, Illinois, 60153
About this study
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
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.
Read the 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.
- Being tested
- Atorvastatin, Methotrexate, Tacrolimus
- Keywords
- Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplastic Syndrome, BMT, Matched unrelated donor transplant, Graft versus Host Disease, GVHD
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Graft vs Host Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
Also called Lipitor
Oral medication given to prevent graft versus host disease in bone marrow transplant.
MethotrexateDrug
Also called Trexall
IV medication given to prevent graft versus host disease in bone marrow transplant.
TacrolimusDrug
Also called Prograft
IV or Oral medication given to prevent graft versus host disease in bone marrow transplant.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Methotrexate; Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 2 years
Secondary outcomes (7)
To determine the cumulative incidence of grade 3 to 4 acute GVHD
National Institutes of Health Acute Graft-Versus-Host Disease Grading and Form
Measured: 100 days
To determine rate of disease relapse
Blood work and/or bone marrow biopsy will be used
Measured: 2 years
To determine non-relapse mortality (NRM)
Blood work and/or bone marrow biopsy will be used
Measured: 2 years
To determine progression-free survival (PFS)
Blood work and/or bone marrow biopsy will be used
Measured: 2 years
To determine overall survival (OS)
Blood work and/or bone marrow biopsy will be used
Measured: 2 years
Number of participants with Grade 4 through 5 Adverse Events that are related to study treatment, grading according to NCI CTCAE Version 4
Toxicities that are possibly, probably, and definitely related
Measured: 30 days of the last dose of protocol treatment
Determine the frequency and severity of chronic GVHD
National Institutes of Health Chronic Graft-Versus-Host Disease Grading and Form
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2017
- Study start10 Dec 2019 (estimated)
- Primary completion28 Feb 2020 (estimated)
- Study completion28 Feb 2021 (estimated)
Why it stopped: No participants were enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, two arms
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loyola University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Patrick Stiff, Loyola University
- Investigators
- Patrick Stiff, MD, Study director, Cardinal Bernardin Cancer Center, Loyola University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03066466
- Sponsor's protocol ID
- 208106
- Status last verified
- Apr 2021
- First submitted
- 23 Feb 2017
- Last updated
- 27 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03066466
- Acronym / sponsor ID
- 208106
- Keywords
- Acute Myeloid Leukemia, Acute Lymphocytic Leukemia, Myelodysplastic Syndrome, BMT, Matched unrelated donor transplant, Graft versus Host Disease, GVHD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No participants were enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Loyola UniversityUniversity, hospital or other
- Study start
- 10 Dec 2019 (estimated)
- Primary completion
- 28 Feb 2020 (estimated)
- Study completion
- 28 Feb 2021 (estimated)
- First posted
- 28 Feb 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Randomized, two arms
| Arm | Type | Receives |
|---|---|---|
| Arm A: Atorvastatin | Experimental | Drug: Atorvastatin, Drug: Methotrexate, Drug: TacrolimusThe 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. |
| Arm B: Standard of Care | Active comparator | Drug: Methotrexate, Drug: TacrolimusPatients 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
- Patients must have Performance Score (PS) greater than 70 percent
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtorvastatinAlso: LipitorOral medication given to prevent graft versus host disease in bone marrow transplant. | Drug | Arm A: Atorvastatin |
| MethotrexateAlso: TrexallIV medication given to prevent graft versus host disease in bone marrow transplant. | Drug | Arm A: Atorvastatin, Arm B: Standard of Care |
| TacrolimusAlso: PrograftIV or Oral medication given to prevent graft versus host disease in bone marrow transplant. | Drug | Arm A: Atorvastatin, Arm B: Standard of Care |
Primary outcome
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
7 secondary outcomes
To determine the cumulative incidence of grade 3 to 4 acute GVHD
Time frame: 100 days
To determine rate of disease relapse
Time frame: 2 years
To determine non-relapse mortality (NRM)
Time frame: 2 years
To determine progression-free survival (PFS)
Time frame: 2 years
To determine overall survival (OS)
Time frame: 2 years
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
Determine the frequency and severity of chronic GVHD
Time frame: 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick Stiff, MD study director
Cardinal Bernardin Cancer Center, Loyola University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Atorvastatin, Methotrexate and Tacrolimus in people with Acute Myeloid Leukemia and Acute Lymphocytic Leukemia, run by Loyola University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 27 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2021.