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Acute Myelogenous LeukemiaPhase 2NCT01491958

Safety & Efficacy of Atorvastatin for Prophylaxis of Acute Graft Versus Host Disease in Patients With Hematological Malignancies HLA- Donor Hematopoietic Stem Cell Transplantation

A Phase 2 study testing atorvastatin, Tacrolimus and methotrexate in people with Acute Myelogenous Leukemia and Acute Lymphocytic Leukemia, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Phase II trial evaluating the safety \& efficacy of Atorvastatin for prophylaxis of Acute Graft Versus Host Disease (GVHD) in patients with hematological malignances undergoing human leukocyte antigen (HLA)-Matched Related Donor Hematopoietic Stem Cell Transplant (HSCT). Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
atorvastatin, Tacrolimus and methotrexate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteUnited States
Study dates
10 Dec 2011to 27 Jun 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Donor Eligibility Criteria
  • The donor must be at least 18 years of age, and willing/able to provide informed consent. Complete medication list will be reviewed for potential negative interaction with atorvastatin.
  • The donor must be an HLA-matched sibling or relative.
  • Syngeneic donors are not eligible.
  • Female donors of child-bearing potential should have a negative pregnancy test, and must not be breast feeding.
  • Bilirubin, AST and ALT must be < 2 x normal; and absence of hepatic fibrosis/cirrhosis.
Show all 26Show fewer
  • Adequate renal function as defined by a serum creatinine clearance of ≥ 40% of normal calculated by Cockcroft-Gault equation.
  • Adequate cardiac function with no history of congestive heart failure, uncontrolled atrial fibrillation or ventricular tachyarrhythmias.
  • Patient Eligibility Criteria
  • Have hematologic malignancy requiring allogeneic HSCT, have adequate organ function, a serologic (or higher resolution) 6/6 class I human leukocyte antigen (HLA)-A and B and molecular class II DRB1 matched related donor, and are able to give informed consent.
  • Patients > 18 and ≤ 65 years with comorbidity score ≤ 3 will be eligible for myeloablative conditioning (MAC), while patients > 65 years of age, those with previous history of autologous transplantation, or high comorbidity index (>3) will be eligible for reduced intensity conditioning (RIC) transplantation .
  • All patients must have at least one 6/6 HLA-matched sibling donor.
  • Patient must provide informed consent
  • Patients must have left ventricular ejection fraction > 30%, no uncontrolled arrhythmias or New York Heart Association class III-IV heart failure.
  • Bilirubin must be < 2 x normal; and absence of hepatic fibrosis/cirrhosis.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must be <2 x normal; and absence of hepatic fibrosis/cirrhosis.
  • Serum creatinine clearance of ≥40% of normal calculated by Cockcroft-Gault equation.
  • Forced expiratory volume in one second (FEV1)and diffusion capacity; corrected for hemoglobin(DLCO) ≥ 50% and 40% of predicted respectively.
  • Karnofsky performance status > 70.
  • A negative pregnancy test will be required for all women of child bearing potential. Breast feeding is not permitted.
  • No HIV infection. Patients with immune dysfunction are at a significantly higher risk of toxicities from intensive immunosuppressive therapies.
  • No evidence of active bacterial, viral or fungal infection at the time of transplant conditioning.
  • No active alcohol or substance abuse within 6 months of study entry.
  • Prior allogeneic transplant is acceptable.
  • No history of intolerance or allergic reactions with atorvastatin or other statins.
  • Patients who have previously been taking atorvastatin or any other statin will be eligible as long as there is no contraindication to switch to atorvastatin 40mg/day in the opinion of the treating physician.

Who cannot join

  • Patients undergoing a T-cell depleted allogeneic transplantation will not be eligible.
  • Patients receiving another investigational drug are not eligible unless cleared by Principal Investigator. Patients with prior malignancies except resected basal cell carcinoma, treated carcinoma in-situ, or other hematologic diseases for which allogeneic HSCT is a treatment strategy, are not eligible. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Principal Investigator.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Ohio State University

    Columbus, Ohio, 43210

Other trials in United States

About this study

Official title: Phase II Trial Evaluating the Safety and Efficacy of Atorvastatin for the Prophylaxis of Acute Graft Versus Host Disease(GVHD) in Patients With Hematological Malignancies Undergoing HLA-Matched Related Donor Hematopoietic Stem Cell Transplantation (HSCT)

Phase II trial evaluating the safety \& efficacy of Atorvastatin for prophylaxis of Acute Graft Versus Host Disease (GVHD) in patients with hematological malignances undergoing human leukocyte antigen (HLA)-Matched Related Donor Hematopoietic Stem Cell Transplant (HSCT).

Read the detailed description

The study is a single-arm phase II single institutional trial evaluating the safety and efficacy of atorvastatin for the prophylaxis of acute GVHD in patients with hematological malignancies undergoing HLA matched related donor HSCT. This study will explore a two-pronged acute GVHD prophylaxis strategy, consisting of pre-treating consenting related donors with atorvastatin before stem cell mobilization and collection, followed by atorvastatin plus methotrexate/tacrolimus-based GVHD prophylaxis in transplant recipient patients.

Keywords
Leukemia, AML, ALL, MDS
Medical subject headings
Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Myelodysplastic Syndromes, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • atorvastatinDrug

    Also called Lipitor

    donors-will receive atorvastatin 40 mg/day orally at least 14 days before anticipated first day of stem cell leukapheresis (LP) until successful completion of leukapheresis according to institutional guidelines.

    Patients-will receive atorvastatin 40 mg starting at least 7 days before initiation of transplant conditioning regimen, to permit a 1 week observation period to rule out any atorvastatin-induced side effects before initiation of transplant conditioning. Patients will continue on atorvastatin with standard GVHD prophylaxis with tacrolimus and methotrexate until end of GVHD prophylaxis according to institutional standard guidelines, or until development of endpoint, which ever should occur first.

  • TacrolimusDrug

    Also called Prograf

    beginning on Day -2 through approximately Day +180 (that is, approximately 6 months after Day 0)

  • methotrexateDrug

    Also called Amethopterin, MTX

    Day +1, +3, and +6 and +11

Study groups in NCT01491958
Study groupRoleWhat they receive
DonorExperimentalRelated donors will receive atorvastatin 40 mg/day orally at least 14 days before anticipated first day of stem cell leukapheresis (LP) until successful completion of leukapheresis according to institutional guidelines. Peripheral blood stem cells will not be manipulated or T-depleted prior to administration.
Receives: Drug: atorvastatin
PatientExperimentalPatients will receive atorvastatin 40 mg starting at least 7 days before initiation of transplant conditioning regimen, to permit a 1 week observation period to rule out any atorvastatin-induced side effects before initiation of transplant conditioning. Patients will continue on atorvastatin with standard GVHD prophylaxis with tacrolimus and methotrexate until end of GVHD prophylaxis according to institutional standard guidelines, or until development of endpoint, which ever should occur first. Standard post transplant care will be administered.
Receives: Drug: atorvastatin; Drug: Tacrolimus; Drug: methotrexate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Grades II to IV aGVHD at Day +100 of Atorvastatin Administration

    The incidence of grades II to IV aGVHD at day +100 of atorvastatin administration. The grading of aGVHD and cGVHD were done using the Consensus Conference criteria.

    Measured: Up through day 100 following transplant

Secondary outcomes (4)

  1. Safety of Atorvastatin in Transplant Recipients in Terms of Adverse Events and Toxicities.

    Adverse events and toxicities were monitored in patients using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria.

    Measured: Patients: Baseline, weekly for 9 weeks and then on days 84, 91-100, 180 and 365. Donors: at apheresis and then 30 days later.

  2. Time to Neutrophil and Platelet Engraftment

    Neutrophil engraftment will be defined as first of three consecutive days with ANC ≥ 0.5 x 109/L post-conditioning regimen induced nadir. Similarly platelet engraftment is defined as first day of platelet count ≥ 20,000 x 109/L, without transfusion for 7 consecutive days.

    Measured: weekly for 12 weeks, 100 days, 6 months, and 12 months

  3. Percentage of Patients With Chronic Graft Versus Host Disease (cGVHD)

    cGVHD occurring anytime after day 100 post transplant will be termed chronic GVHD, and evaluated in patients who were followed for at least 100 days without early progression or death. Grading of cGVHD was done using the National Institutes of Health Consensus Development Project Criteria

    Measured: up 1 year post transplant

  4. Non Relapse Mortality (NRM) at One Year

    Cumulative incidence of NRM will be calculated as the time from transplant until death not related to disease, where the competing risk for NRM was death due to disease. Patients who had not died were censored at last follow up.

    Measured: up to 12 months post transplant

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Dec 2011 (estimated)
  2. Study start10 Dec 2011
  3. Primary completion1 Jan 2014
  4. Study completion27 Jun 2016

Resources

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 2
Primary purpose
Supportive care
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01491958
Sponsor's protocol ID
OSU-11004
Other IDs
NCI-2011-03590
Status last verified
Jan 2018
First submitted
9 Dec 2011
Last updated
23 Jan 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing atorvastatin, Tacrolimus and methotrexate in people with Acute Myelogenous Leukemia and Acute Lymphocytic Leukemia, run by Ohio State University Comprehensive Cancer Center 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 26 inclusion and 2 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: finished, as of the sponsor's last update on 23 Jan 2018. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With Grades II to IV aGVHD at Day +100 of Atorvastatin Administration (time frame: Up through day 100 following transplant). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01491958.

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 23 Jan 2018.

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