Graft-Versus-Host Disease (GVHD) Acute on ChronicPhase 1/2NCT01523821
Alpha 1 Anti-Trypsin (AAT) in Treating Patients With Acute Graft-Versus-Host Disease GVHD)
A Phase 1/2 study testing Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] in people with Graft-Versus-Host Disease (GVHD) Acute on Chronic, run by Fred Hutchinson Cancer Center at 1 site in United States.
Trial summary
This phase I/II trial evaluates the efficacy and adverse effects of alpha 1 anti-trypsin (AAT) for the treatment of acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft-Versus-Host Disease (GVHD) Acute on Chronic
- What is being tested?
- Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia]
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 11 Oct 2013to 15 Jan 2017
- Phase
- Phase 1/2
- 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
- Patients transplanted from related or unrelated, human leukocyte antigen (HLA) matched or mismatched donors
- Patients transplanted with hematopoietic stem cells from any source
- Patients receiving calcineurin inhibitors as part of graft versus host disease (GVHD) prophylaxis
- Patients with acute GVHD grades II-IV developing despite GVHD prophylaxis
- Patients who have not shown a satisfactory response to methylprednisolone-equivalent doses at 2 mg/kg/day, based on adjusted body weight
- Signed and dated informed consent
Who cannot join
- Patients who have received any systemic agents in addition to steroids for treatment of GVHD
- Patients unable to give informed consent
- Patients with manifestations of classic chronic GVHD
- Patients with evidence of recurrent malignancy
- Patients with acute/chronic GVHD overlap syndrome
- Patients whose GVHD developed after donor lymphocyte infusion (DLI)
Show all 12Show fewer
- Patients with severe organ dysfunction, defined as
- On dialysis
- Requiring oxygen (O2) at more than 2 l/min
- Uncontrolled arrhythmia or heart failure
- Veno-occlusive disease (sinusoidal obstruction syndrome)
- Patients with uncontrolled infections
Trial locations and contacts
1 site in 1 country.
United States1 site
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109
About this study
Official title: Treatment of Steroid Non-responsive Acute GVHD With Alpha 1 Antitrypsin (AAT). A Phase I/II Study
This phase I/II trial evaluates the efficacy and adverse effects of alpha 1 anti-trypsin (AAT) for the treatment of acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the safety and tolerability of AAT in patients with steroid non-responsive acute GVHD.
II. Characterize pharmacodynamic effects of AAT on pro-inflammatory cytokines, heparan sulfate, and the spectrum of peripheral blood T cells.
III. Determine clinical responses of GVHD to AAT in patients with steroid non-responsive acute GVHD.
OUTLINE: This is a phase I/II dose-escalation study of AAT.
Patients will receive AAT intravenously (IV) on study days 1, 3, 5, and 7. Patients who experience no toxicity and in whom GVHD is stable or improved after the day 7 dose can continue therapy with AAT on days 9, 11, 13 and 15 for a total of 8 doses.
- Being tested
- Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia]
- 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-Proteinase Inhibitor, Human 1 MG [Glassia]Drug
Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] at various levels over different days
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (30 mg/kg) | Other | Alpha 1 anti-trypsin (AAT) will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) every other day (QOD) on days 3, 5, 7, 9, 11, 13 \& 15. Receives: Drug: Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] |
| Cohort 2 (60 mg/kg) | Other | AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. Receives: Drug: Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] |
| Cohort 3 (90 mg/kg) | Other | AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. Receives: Drug: Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number (Percentage) of Patients at Each Dosing Cohort Who Experience no Toxicity and in Whom Graft Versus Host Disease (GVHD) is Stable or Improved
Toxicity and adverse events were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. All adverse events were reported regardless of attribution to alpha 1 anti-trypsin (AAT). GVHD response was defined per standard criteria for improvement, no change or progression of signs/symptoms in skin rash (% body surface area), GI (nausea, vomiting, anorexia, diarrhea, GI bleeding, abdominal cramping) and hepatic function (serum bilirubin levels). For this outcome measure, the requirement for additional GVHD treatment beyond AAT was not included in the criteria for response (i.e patients who may have required additional GVHD treatment before study day 28 were not automatically categorized as non-responders or as having progressive GVHD).
Measured: Adverse events were reported through 15 days after the last dose of AAT. GVHD response assessed at study day 28.
Secondary outcomes (5)
Number (Percentage) of Patients at Each Dosing Cohort Experiencing an Unexpected Serious Adverse Event (SAE)
Serious adverse events included death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/ incapacity, or congenital anomaly/birth defect. Significant events that do not meet these criteria may be considered serious if they jeopardize the patient and require a medical intervention to prevent one of the outcomes above. An "unexpected" adverse event is defined as an event that is not identified in nature, severity or frequency in the current investigator brochure/package insert/product information.
Measured: SAEs were reported through 30 days after the last dose of alpha 1 anti-trypsin (AAT).
Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Suspected Serious Adverse Reactions (Infusion Related Reactions)
Serious adverse reactions were assessed by the NCI CTCAE v4.0.
Measured: Within 48 hours after each infusion
Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Thrombotic or Thrombo-embolic Events
Events were assessed using the NCI CTCAE v4.0.
Measured: Events were reported through 15 days after the last dose of AAT.
Number (Percentage) of Patients at Each Dosing Cohort With Occurrence of Infections
Infections were assessed using NCI CTCAE v4.0.
Measured: Infections were reported through 15 days after the last dose of AAT.
Number (Percentage) of Patients at Each Dosing Cohort With Progression of GVHD
GVHD responses were assessed using criteria established by the Center for International Blood and Marrow Transplant Research and criteria from the Acute GVHD Activity Index. Patients who required additional systemic GVHD treatment beyond AAT before study day 28 were defined as having progressive GVHD.
Measured: GVHD responses were assessed on day 28 after starting AAT therapy or at time of death if patient died before study day 28.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2012 (estimated)
- Study start11 Oct 2013
- Primary completion15 Jan 2017
- Study completion15 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft-Versus-Host Disease (GVHD) Acute on ChronicStudies of the same condition, open and under way.
- More trials run by Fred Hutchinson Cancer CenterThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- The study will have three escalating alpha 1 anti-trypsin (AAT) dose cohorts with six patients in each cohort (Phase I). Based on response and toxicity, an additional six patients will be enrolled in the optimal dose (Phase II).
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fred Hutchinson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- H. Joachim Deeg, Principal investigator, Fred Hutch/University of Washington Cancer Consortium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01523821
- Sponsor's protocol ID
- 2571.00
- Other IDs
- NCI-2011-03805, 2571, 2571.00, P01HL036444, P30CA015704
- Status last verified
- Oct 2018
- First submitted
- 23 Jan 2012
- Last updated
- 30 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Steroid Non-responsive Acute GVHD With Alpha 1 Antitrypsin (AAT). A Phase I/II Study
- ClinicalTrials.gov ID
- NCT01523821
- Acronym / sponsor ID
- 2571.00
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Fred Hutchinson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 11 Oct 2013 (actual)
- Primary completion
- 15 Jan 2017 (actual)
- Study completion
- 15 Jan 2017 (actual)
- First posted
- 1 Feb 2012 (estimated)
- Results
- Posted 30 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I/II trial evaluates the efficacy and adverse effects of alpha 1 anti-trypsin (AAT) for the treatment of acute graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation.
Detailed description
PRIMARY OBJECTIVES:
- Determine the safety and tolerability of AAT in patients with steroid non-responsive acute GVHD.
II. Characterize pharmacodynamic effects of AAT on pro-inflammatory cytokines, heparan sulfate, and the spectrum of peripheral blood T cells.
III. Determine clinical responses of GVHD to AAT in patients with steroid non-responsive acute GVHD.
OUTLINE: This is a phase I/II dose-escalation study of AAT.
Patients will receive AAT intravenously (IV) on study days 1, 3, 5, and 7. Patients who experience no toxicity and in whom GVHD is stable or improved after the day 7 dose can continue therapy with AAT on days 9, 11, 13 and 15 for a total of 8 doses.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- The study will have three escalating alpha 1 anti-trypsin (AAT) dose cohorts with six patients in each cohort (Phase I). Based on response and toxicity, an additional six patients will be enrolled in the optimal dose (Phase II).
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (30 mg/kg) | Other | Drug: Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia]Alpha 1 anti-trypsin (AAT) will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 30mg/kg (maintenance dose) every other day (QOD) on days 3, 5, 7, 9, 11, 13 \& 15. |
| Cohort 2 (60 mg/kg) | Other | Drug: Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia]AAT will be administered intravenously at a dose of 90 mg/kg (loading dose) on day 1 followed by 60 mg/kg (maintenance dose) QOD on days 3, 5, 7, 9, 11, 13 \& 15. |
| Cohort 3 (90 mg/kg) | Other | Drug: Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia]AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients transplanted from related or unrelated, human leukocyte antigen (HLA) matched or mismatched donors
- Patients transplanted with hematopoietic stem cells from any source
- Patients receiving calcineurin inhibitors as part of graft versus host disease (GVHD) prophylaxis
- Patients with acute GVHD grades II-IV developing despite GVHD prophylaxis
- Patients who have not shown a satisfactory response to methylprednisolone-equivalent doses at 2 mg/kg/day, based on adjusted body weight
Key exclusion criteria (12 listed)
- Patients who have received any systemic agents in addition to steroids for treatment of GVHD
- Patients unable to give informed consent
- Patients with manifestations of classic chronic GVHD
- Patients with evidence of recurrent malignancy
- Patients with acute/chronic GVHD overlap syndrome
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 |
|---|---|---|
| Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia]Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] at various levels over different days | Drug | Cohort 1 (30 mg/kg), Cohort 2 (60 mg/kg), Cohort 3 (90 mg/kg) |
Primary outcome
Number (Percentage) of Patients at Each Dosing Cohort Who Experience no Toxicity and in Whom Graft Versus Host Disease (GVHD) is Stable or Improved
Time frame: Adverse events were reported through 15 days after the last dose of AAT. GVHD response assessed at study day 28.
Toxicity and adverse events were assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. All adverse events were reported regardless of attribution to alpha 1 anti-trypsin (AAT). GVHD response was defined per standard criteria for improvement, no change or progression of signs/symptoms in skin rash (% body surface area), GI (nausea, vomiting, anorexia, diarrhea, GI bleeding, abdominal cramping) and hepatic function (serum bilirubin levels). For this outcome measure, the requirement for additional GVHD treatment beyond AAT was not included in the criteria for response (i.e patients who may have required additional GVHD treatment before study day 28 were not automatically categorized as non-responders or as having progressive GVHD).
5 secondary outcomes
Number (Percentage) of Patients at Each Dosing Cohort Experiencing an Unexpected Serious Adverse Event (SAE)
Time frame: SAEs were reported through 30 days after the last dose of alpha 1 anti-trypsin (AAT).
Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Suspected Serious Adverse Reactions (Infusion Related Reactions)
Time frame: Within 48 hours after each infusion
Number (Percentage) of Patients at Each Dosing Cohort Who Experience One or More Thrombotic or Thrombo-embolic Events
Time frame: Events were reported through 15 days after the last dose of AAT.
Number (Percentage) of Patients at Each Dosing Cohort With Occurrence of Infections
Time frame: Infections were reported through 15 days after the last dose of AAT.
Number (Percentage) of Patients at Each Dosing Cohort With Progression of GVHD
Time frame: GVHD responses were assessed on day 28 after starting AAT therapy or at time of death if patient died before study day 28.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
H. Joachim Deeg principal investigator
Fred Hutch/University of Washington Cancer Consortium
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] in people with Graft-Versus-Host Disease (GVHD) Acute on Chronic, run by Fred Hutchinson 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 6 inclusion and 12 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 30 Oct 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 30 Oct 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?
Number (Percentage) of Patients at Each Dosing Cohort Who Experience no Toxicity and in Whom Graft Versus Host Disease (GVHD) is Stable or Improved (time frame: Adverse events were reported through 15 days after the last dose of AAT. GVHD response assessed at study day 28.). 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 30 Oct 2018.