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Alpha 1 Anti-Trypsin in Treating Patients With Acute Graft-Versus-Host Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborators:
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01523821
First received: January 23, 2012
Last updated: November 18, 2016
Last verified: November 2016
  Purpose
This phase I/II trial studies the side effects and best dose of alpha 1 anti-trypsin (alpha-1-proteinase inhibitor human) and to see how well it works in treating patients with acute graft-versus-host disease (GVHD). Alpha-1-proteinase inhibitor human may be a better treatment for graft-versus-host disease caused by a stem cell transplant.

Condition Intervention Phase
Graft Versus Host Disease
Biological: Alpha-1-Proteinase Inhibitor Human
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Treatment of Steroid Non-responsive Acute GVHD With Alpha 1 Antitrypsin (AAT). A Phase I/II Study

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Number (percentage) of patients at each dosing cohort who experience no toxicity and in whom GVHD is stable or improved [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
    Toxicity and adverse events will be assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0.


Secondary Outcome Measures:
  • Number (percentage) of patients at each dosing cohort experiencing an unexpected severe adverse event [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
    Toxicity and adverse events will be assessed by the NCI CTCAE v4.0.

  • Number (percentage) of patients at each dosing cohort who experience one or more suspected serious adverse reactions or serious adverse reactions [ Time Frame: Up to 30 days ] [ Designated as safety issue: Yes ]
    Toxicity and adverse events will be assessed by the NCI CTCAE v4.0.

  • Number (percentage) of patients at each dosing cohort who experience one or more thrombotic or thrombo-embolic events [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
  • Number (percentage) of patients at each dosing cohort with occurrence of infections [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
  • Number (percentage) of patients at each dosing cohort with progression of GVHD [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    GVHD responses assessed by Center for International Bone Marrow Transplantation Research criteria.

  • Plasma concentrations of alpha-1-proteinase inhibitor human at each dosing cohort [ Time Frame: Baseline to day 17 ] [ Designated as safety issue: No ]
  • Pro-inflammatory cytokine levels at the messenger ribonucleic acid (by polymerase chain reaction) and protein (by enzyme-linked immunosorbent assay) levels at each dosing cohort [ Time Frame: Baseline to 15 days ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: November 2013
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (GVHD therapy)
Patients receive alpha-1-proteinase inhibitor human IV on days 1, 3, 5, and 7. Patients who experience no toxicity and in whom GVHD is stable or improved by Day 7 can continue therapy with alpha 1 anti-trypsin on days 9, 11, 13 and 15.
Biological: Alpha-1-Proteinase Inhibitor Human
Given IV
Other Names:
  • .ALPHA.1-PROTEINASE INHIBITOR HUMAN
  • A1AT
  • A1PI
  • AAT
  • Alpha 1 Antitrypsin
  • Alpha-1 Antitrypsin
  • Alpha-1-Antiproteinase
  • Aralast
  • Prolastin-C
Other: Laboratory Biomarker Analysis
Correlative studies
Other: Pharmacological Study
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the safety and tolerability of alpha 1 anti-trypsin (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, dose-escalation study of alpha 1 proteinase inhibitor human followed by a phase II study.

Patients receive alpha-1-proteinase inhibitor human intravenously (IV) on 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 alpha-1-proteinase inhibitor human on days 9, 11, 13 and 15.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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 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

Exclusion Criteria:

  • 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)
  • Patients with severe organ dysfunction

    • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01523821

Locations
United States, North Carolina
Duke University Medical Center Withdrawn
Durham, North Carolina, United States, 27710
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: H. Joachim Deeg    206-667-5985    jdeeg@fredhutch.org   
Principal Investigator: H. Joachim Deeg         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: H. Joachim Deeg Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01523821     History of Changes
Other Study ID Numbers: 2571.00  NCI-2011-03805  2571  2571.00  P01HL036444  P30CA015704 
Study First Received: January 23, 2012
Last Updated: November 18, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Alpha 1-Antitrypsin
Protein C Inhibitor
Protease Inhibitors
Trypsin Inhibitors
Serine Proteinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 07, 2016