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Graft-versus-host-diseasePhase 2NCT03459040

A Proof of Concept Pilot Trial of Alpha-1-Antitrypsin for Pre-Emption Of Steroid-Refractory Acute GVHD

A Phase 2 study testing Alpha 1-Antitrypsin in people with Graft-versus-host-disease and GVHD, run by John Levine at 5 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

Bone marrow transplant (BMT) patients can develop graft-versus-host disease (GVHD), a serious and potentially fatal complication. The researchers have developed a blood test to identify patients most at risk for developing severe GVHD. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft-versus-host-disease, GVHD
What is being tested?
Alpha 1-Antitrypsin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
5 sitesUnited States
Study dates
17 Aug 2018to 21 Aug 2020
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

  • High risk prediction score as determined by the Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm at either day 7 or day 14 post Hematopoietic cell transplant (HCT).
  • Any donor type (e.g., related, unrelated) or stem cell source (bone marrow, peripheral blood, cord blood).
  • Donor and recipient match each other for at least 7/8 HLA-loci (HLA-A, B, C, and DR)
  • Any conditioning regimen (non-myeloablative, myeloablative, or reduced intensity) is acceptable.
  • GVHD prophylaxis must include a calcineurin inhibitor combined with methotrexate or mycophenolate.
  • The use of serotherapy to prevent GVHD (e.g., antithymocyte globulin) prior to day 3 post-HCT is permitted
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  • Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert syndrome within 3 days prior to enrollment.
  • ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days prior to enrollment.
  • Signed and dated written informed consent obtained from patient or legal representative.

Who cannot join

  • Patients who develop acute GVHD prior to start of study drug
  • Patients at very high risk for relapse post HCT as defined by very high disease risk index
  • Patients participating in a clinical trial where prevention of GVHD is the primary endpoint
  • Uncontrolled active infection (i.e., progressive symptoms related to infection despite treatment or persistently positive microbiological cultures despite treatment or any other evidence of severe sepsis)
  • Patients who are pregnant
  • Patients on dialysis within 7 days of enrollment
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  • Patients requiring ventilator support or oxygen supplementation exceeding 40% FiO2 within 14 days of enrollment.
  • Patients receiving investigational agent within 30 days of enrollment. However, the Principal Investigator (PI) may approve prior use of an investigational agent if the agent is not expected to interfere with the safety or the efficacy of alpha-1-antitrypsin.
  • History of allergic reaction to alpha-1-antitrypsin

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Ohio State University

    Columbus, Ohio, 43210

  • City of Hope

    Duarte, California, 91010

  • Vanderbilt University

    Nashville, Tennessee, 37232

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

Other trials in United States

About this study

Bone marrow transplant (BMT) patients can develop graft-versus-host disease (GVHD), a serious and potentially fatal complication. The researchers have developed a blood test to identify patients most at risk for developing severe GVHD. Patients who consent to this study will have their blood tested up to two times after BMT to determine if they are at high risk for severe GVHD. The tests will be performed one week and two weeks after BMT. Patients who are high risk will be treated with a drug called alpha-1-antitrypsin (AAT) to see if it prevents the development of severe GVHD. Patients will receive 16 doses of AAT through a catheter placed into a blood vessel over eight weeks. AAT will be given either in the hospital or the outpatient clinic two times per week. Patients will be followed for the development of severe GVHD for up to four months from the BMT and will continue to be followed at routine clinic visits for up to one year after BMT.

Being tested
Alpha 1-Antitrypsin
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-AntitrypsinDrug

    Also called AAT

    AAT will be given either in the hospital or the outpatient clinic two times per week.

Study groups in NCT03459040
Study groupRoleWhat they receive
alpha-1-antitrypsin (AAT)Experimental16 doses of AAT through a catheter placed into a blood vessel over eight weeks.
Receives: Drug: Alpha 1-Antitrypsin

What is being measured

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

  1. Number of High Risk Patients Who Develop Steroid Refractory GVHD

    Number of High Risk patients who develop steroid refractory GVHD by day 100 post Hematopoietic cell transplant (HCT) .

    Steroid refractory GVHD defined as patients who did not achieve Complete Response (CR) or Partial Response (PR) by day 28 of systemic steroid treatment OR if additional immunosuppression beyond steroids was given for treatment of GVHD prior to 28 days of steroid treatment.

    • CR: All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR on day 28, the patient must be in CR on that day and have had no intervening additional GVHD therapy.
    • PR: An improvement in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR on day 28, the patient must be in PR on that day and have had no intervening additional GVHD therapy.

    Measured: Day 100 post HCT.

Secondary outcomes (8)

  1. Number of Participants Alive at 6 Months and 1 Year

    Overall survival - The number of that patients are still alive from the start of treatment at 6 months and 1 year

    Measured: 6 months and 1 year

  2. Number of Participants With Non-relapse Mortality (NRM)

    Number of participants with NRM - deaths which could not be attributed to disease relapse or progression. Non-relapse mortality defined as death without prior relapse.

    Measured: 6 months and 1 year

  3. Number of Participants With Relapse

    Number of participants with relapse at one year. Relapse defined as recurrence of disease that required transplant.

    Measured: 1 year

  4. Number of Participants With Clinically Relevant GVHD States Grade II-IV GVHD

    Number of participants with clinically relevant GVHD states grade II-IV GVHD requiring systemic treatment.

    GVHD grades II-IV are defined as

    • Rash covering more than 50% of the body surface area, AND/OR
    • Total bilirubin > 2 mg/dl AND/OR
    • Persistent nausea or vomiting, AND/OR
    • Diarrhea > 500 ml/day AND/OR
    • Severe abdominal pain requiring treatment or blood present in the diarrhea

    Measured: 100 days

  5. Number of Participants Achieving Overall Response

    For patients who develop GVHD prior to day 100 post-HCT, the number of participants achieving overall response. The overall response rate = complete remission and partial remission (CR + PR) 28 days after initiation of systemic steroid treatment.

    Measured: Day 28

  6. Number of Participants With Severe GI GVHD Stage 3 or 4

    Number of participants with severe GI GVHD stage 3 or 4. GI GVHD stage 3 or 4 is defined as diarrhea >1000 ml/day OR severe abdominal pain requiring treatment OR blood present in the diarrhea.

    Measured: By day 100 post-HCT

  7. Number of Participants With Chronic GVHD Requiring Systemic Steroid Treatment

    Number of participants with chronic GVHD requiring systemic steroid treatment. Chronic GVHD Requiring Systemic Steroid Treatment: defined as the development of symptoms of chronic GVHD according to NIH Consensus Criteria that require treatment with oral or intravenous corticosteroids.

    Measured: 1 year

  8. Number of Participants With Serious Infections

    Number of participants with serious infections (defined as grade 3 by the Blood and Marrow Transplant Clinical Trials Network). Serious Infection: Defined as bacterial, fungal, viral or parasitic infections that required oral or intravenous treatments such as antibiotics.

    Measured: 1 year

Timeline

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

  1. First posted8 Mar 2018
  2. Study start17 Aug 2018
  3. Primary completion21 Aug 2020
  4. Study completion21 Aug 2020

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
Prevention
Allocation
Not applicable
Intervention model
Single group
Model description
Open label single arm
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03459040
Sponsor's protocol ID
GCO 17-2666
Other IDs
P01CA039542
Status last verified
Jun 2021
First submitted
2 Mar 2018
Last updated
12 Jul 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Gergoudis SC, DeFilipp Z, Ozbek U, Sandhu KS, Etra AM, Choe HK, Kitko CL, Ayuk F, Aziz M, Baez J, Ben-David K, Bunworasate U, Gandhi I, Hexner EO, Hogan WJ, Holler E, Kasikis S, Kowalyk SM, Lin JY, Merli P, Morales G, Nakamura R, Reshef R, Rosler W, Srinagesh H, Young R, Chen YB, Ferrara JLM, Levine JE. Biomarker-guided preemption of steroid-refractory graft-versus-host disease with alpha-1-antitrypsin. Blood Adv. 2020 Dec 22;4(24):6098-6105. doi: 10.1182/bloodadvances.2020003336.

    PubMed 33351103

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alpha 1-Antitrypsin in people with Graft-versus-host-disease and GVHD, run by John Levine at 5 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 9 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 12 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 24 May 2021). 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?

Number of High Risk Patients Who Develop Steroid Refractory GVHD (time frame: Day 100 post HCT.). 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 NCT03459040, 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 12 Jul 2021.

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