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Graft vs Host DiseasePhase 2NCT01700036

A Pilot Study of Alpha-1-Antitrypsin (AAT) in Steroid Refractory Acute Graft vs Host Disease

A Phase 2 study testing Alpha-1-Antitrypsin (AAT) in people with Graft vs Host Disease, run by University of Michigan Rogel Cancer Center at 2 sites 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

This clinical trial will study the safety and efficacy of using the drug Zemaira, an Alpha 1-Antitrypsin (AAT) medication (also known as an Alpha1-Proteinase Inhibitor [Human]) for the treatment of steroid refractory GVHD. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft vs Host Disease
What is being tested?
Alpha-1-Antitrypsin (AAT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
2 sitesUnited States
Study dates
Jul 2013to 26 Oct 2018
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >18 years
  • Patients must have clinical evidence* of steroid-refractory acute Graft vs Host Disease (any organ) defined as one of the following:
  • No change or progression in the stage of skin GvHD after at least 1 week of 2mg/kg/day methylprednisolone (or po equivalent)
  • lack of response of visceral (liver, GI) GvHD despite treatment with 2mg/kg/day methylprednisolone for at least 72h.
  • progression of visceral GvHD despite treatment with 2mg/kg/day methylprednisolone for at least 48h
  • visceral GvHD progressing to stage 4 after 24h of 2mg/kg/d methylprednisolone
Show all 9Show fewer
  • Patients with protracted acute GvHD who have not responded to at least 0.5mg/kg/d of prednisone are considered eligible.
  • Ability to understand and the willingness to sign a written informed consent document.
  • * As GvHD is a clinical diagnosis, and patients will have already been initiated on steroid therapy at the discretion of the attending physician, tissue confirmation of refractory GvHD by biopsy is not required for entry to this study. It is anticipated that most, but not all, patients will have undergone tissue confirmation of the initial diagnosis of GvHD; however lack of tissue confirmation for this clinical syndrome is not exclusionary.

Who cannot join

  • As patients with steroid refractory acute GvHD are quite ill with multiple abnormal labs and organ dysfunction, there are no explicit laboratory values or degree of organ dysfunction that specifically preclude enrollment on this study. Baseline lab studies will be obtained and followed throughout this trial as the standard of care for patients with GvHD.
  • Pregnancy or Nursing Mother
  • Vasopressor requirement
  • Patients may not be receiving any other investigational agents for the treatment of GvHD at time of study entry or at any time while on study or be on another investigational agent that can impact on the primary clinical outcome analyses or has known pharmacodynamics or pharmacokinetic effects on AAT.
  • Patients with known antibodies to IgA

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Michigan Cancer Center

    Ann Arbor, Michigan, 48109

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

This clinical trial will study the safety and efficacy of using the drug Zemaira, an Alpha 1-Antitrypsin (AAT) medication (also known as an Alpha1-Proteinase Inhibitor [Human]) for the treatment of steroid refractory GVHD.

For bone marrow transplant patients, the most common, serious complication is Graft vs Host Disease (GVHD), which at its most severe is a life-threatening, complication and a significant cause of treatment related death, following stem cell transplantation. GVHD is a major obstacle to the overall success of transplant treatment, a strategy that would otherwise provide the possibility of a cure for patients with blood cancers or severe blood disorders. GVHD primarily affects the skin, gut, and liver of the recipient, and involves the interaction of the recipient's (the host's) cells and tissues with the donor's immune system cells that see the host tissues as foreign, and attack the host's cells resulting in tissue and organ damage.

Read more

The severity of acute GvHD ranges from mild to severe, and for patients who don't respond to steroid therapy, the complication is nearly always fatal, either from organ damage or opportunistic infection as a consequence of high dose, steroid treatments.

There is currently no known effective therapy for patients with acute graft vs host disease that's refractory (nonresponsive) to steroid therapy. As stated earlier,the overwhelming majority of these patients may ultimately die from infection. The incidence of acute GvHD that requires intervention, is higher for unrelated donor transplants, the most common treatment option available, and therefore, these patients are at higher risk for treatment related complications from GVHD. Approximately 20,000 unrelated donor transplants are performed each year. The magnitude of this problem then is significant for patients who otherwise might be cured of their blood cancer or disease.

Being tested
Alpha-1-Antitrypsin (AAT)
Medical subject headings
Graft vs Host Disease

What participants receive

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

  • Alpha-1-Antitrypsin (AAT)Drug

    Also called Zemaira

    AAT (Zemaira) will be administered at a dose of 60mg/kg (actual weight) on D1, 4, 8, 12, 16, 20, 24, and 28. A second course of treatment will not be given.

Study groups in NCT01700036
Study groupRoleWhat they receive
Treatment armExperimentalAlpha-1-Antitrypsin (AAT) for the treatment of Steroid Refractory Acute Graft vs Host Disease.
Receives: Drug: Alpha-1-Antitrypsin (AAT)

What is being measured

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

  1. Percentage of Patients That Respond to Treatment

    To estimate the proportion of patients with steroid refractory acute Graft vs Host Disease) GvHD who respond (achieve either PR or CR) to Alpha-1 Antitrypsin (AAT) at a dose of 60mg/kg twice weekly for 8 doses

    Partial Response (PR) is defined as a decrease of at least one grade in the severity of GVHD without deterioration of any organ systems by d28 of therapy.

    Complete Response (CR) is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.

    Measured: 4 weeks

Secondary outcomes (5)

  1. Percentage of Patients Who Achieve a Complete Response to Treatment

    To estimate the proportion of patients in complete remission without additional therapy at four weeks after the last dose of AAT

    Complete remission is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.

    Measured: 4 weeks

  2. Percentage of Patients With Documented Infection

    To estimate the incidence of infection during and following treatment of steroid refractory acute GVHD with AAT

    Measured: 30 days

  3. The Percentage of Patients Alive at 6 Months for Patients in CR or PR

    Survival at 6 months in patients receiving AAT treatment for steroid refractory acute GVHD for patients that achieved a CR or PR.

    Partial Response (PR) is defined as a decrease of at least one grade in the severity of GVHD without deterioration of any organ systems by d28 of therapy.

    Complete Response (CR) is defined as the resolution of all manifestations of GVHD by d28 of treatment. All organs must have a Stage 0.

    Measured: 6 months

  4. Mean Fold Change in Plasma Biomarkers

    The fold change in levels of plasma biomarkers IL-6, TNF-alpha and ST2 will be measured pre-treatment and after the administration of AAT treatment for steroid refractory GvHD.

    Measured: Baseline, 2 weeks, and 4 weeks

  5. Mean Plasma Levels for Alpha-1-Antitrypsin (AAT)

    Plasma levels of Alpha-1-Antitrypsin(AAT)will be measured.

    Measured: 4 weeks

Timeline

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

  1. First posted4 Oct 2012 (estimated)
  2. Study startJul 2013
  3. Primary completionOct 2016
  4. Study completion26 Oct 2018

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
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01700036
Sponsor's protocol ID
umcc 2012.043
Other IDs
HUM 67889
Status last verified
Oct 2018
First submitted
2 Oct 2012
Last updated
27 Nov 2018
Data monitoring committee
Yes

Publications

  • Magenau JM, Goldstein SC, Peltier D, Soiffer RJ, Braun T, Pawarode A, Riwes MM, Kennel M, Antin JH, Cutler CS, Ho VT, Alyea EP 3rd, Parkin BL, Yanik GA, Choi SW, Lewis EC, Dinarello CA, Koreth J, Reddy P. alpha1-Antitrypsin infusion for treatment of steroid-resistant acute graft-versus-host disease. Blood. 2018 Mar 22;131(12):1372-1379. doi: 10.1182/blood-2017-11-815746. Epub 2018 Feb 2.

    PubMed 29437593

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alpha-1-Antitrypsin (AAT) in people with Graft vs Host Disease, run by University of Michigan Rogel Cancer Center at 2 sites 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 9 inclusion and 5 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 27 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 5 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 Patients That Respond to Treatment (time frame: 4 weeks). 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 NCT01700036, which also lists 1 linked publication.

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 Nov 2018.

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