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

This study is currently recruiting participants.
Verified November 2013 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01523821
First received: January 23, 2012
Last updated: November 22, 2013
Last verified: November 2013
  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 an effective treatment for graft-versus-host disease caused by a stem cell transplant.


Condition Intervention Phase
Graft Versus Host Disease
Other: laboratory biomarker analysis
Other: pharmacological study
Biological: alpha-1-proteinase inhibitor human
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:
  • Change in plasma concentrations of alpha-1-proteinase inhibitor human at each dosing cohort [ Time Frame: Baseline to 48 hours following administration of alpha-1-proteinase inhibitor human ] [ Designated as safety issue: No ]
  • Changes in pro-inflammatory cytokine levels at the messenger ribonucleic acid (mRNA) (by > polymerase chain reaction [PCR]) and protein (by enzyme-linked immunosorbent assay [ELISA]) levels at each dosing cohort [ Time Frame: Baseline to 15 days ] [ 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 (CIBMTR) criteria.

  • 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.


Estimated Enrollment: 24
Study Start Date: February 2012
Estimated Primary Completion Date: December 2015 (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, 7, 9, and 11. 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.
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Biological: alpha-1-proteinase inhibitor human
Given IV
Other Names:
  • A1AT
  • A1P1
  • AAT
  • alpha 1 antitrypsin
  • alpha-1 antitrypsin

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 dose-escalation study.

Patients receive alpha-1-proteinase inhibitor human intravenously (IV) on days 1, 3, 5, 7, 9, and 11. Patients who experience no toxicity and in whom GVHD is stable or improved by Day 7 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
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 with ongoing clinical manifestation of GVHD despite primary therapy with steroids (methylprednisolone doses = 2mg/kg/day for at least 5 days)
  • Signed and dated informed consent

Exclusion Criteria:

  • Patients who have received any agents in addition to steroids for therapy 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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01523821

Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: H. Joachim Deeg    206-667-5985      
Principal Investigator: H. Joachim Deeg         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: H. Joachim Deeg Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01523821     History of Changes
Other Study ID Numbers: 2571.00, NCI-2011-03805, 2571.00, P30CA015704, P01HL036444
Study First Received: January 23, 2012
Last Updated: November 22, 2013
Health Authority: United States: Federal Government
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
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014