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

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01523821
First received: January 23, 2012
Last updated: December 17, 2012
Last verified: December 2012
History of Changes
  Purpose

This phase I/II trial studies the side effects and best dose of alpha 1 anti-trypsin and to see how well it works in treating patients with acute graft-versus-host disease (GVHD). Alpha 1 anti-trypsin 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 antitrypsin
 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 Anti-trypsin (AAT). A Phase I/II Study.

Resource links provided by NLM:

U.S. FDA Resources

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

Primary Outcome Measures:
  • Achievement of targeted alpha 1 anti-trypsin plasma concentrations [ Time Frame: After dose 1 (24 or 48 hour interval) ] [ Designated as safety issue: No ]
    Alpha 1 anti-trypsin target concentrations indicated are based on pilot data and the intended suppression of pro-inflammatory cytokines by >= 50%. Stool concentrations of AAT will be measured to determine the effect of IV administered AAT on the expected healing of the intestinal mucosa and the loss of AAT in the stool.

  • Achievement of targeted alpha 1 anti-trypsin plasma concentrations [ Time Frame: After dose 2 (24 or 48 hour interval) ] [ Designated as safety issue: No ]
    Alpha 1 anti-trypsin target concentrations indicated are based on pilot data and the intended suppression of pro-inflammatory cytokines by >= 50%. Stool concentrations of AAT will be measured to determine the effect of IV administered AAT on the expected healing of the intestinal mucosa and the loss of AAT in the stool.

  • Achievement of targeted alpha 1 anti-trypsin plasma concentrations [ Time Frame: After dose 3 (24 or 48 hour interval) ] [ Designated as safety issue: No ]
    Alpha 1 anti-trypsin target concentrations indicated are based on pilot data and the intended suppression of pro-inflammatory cytokines by >= 50%. Stool concentrations of AAT will be measured to determine the effect of IV administered AAT on the expected healing of the intestinal mucosa and the loss of AAT in the stool.

  • Achievement of targeted alpha 1 anti-trypsin plasma concentrations [ Time Frame: After dose 6 (24 or 48 hour interval) ] [ Designated as safety issue: No ]
    Alpha 1 anti-trypsin target concentrations indicated are based on pilot data and the intended suppression of pro-inflammatory cytokines by >= 50%. Stool concentrations of AAT will be measured to determine the effect of IV administered AAT on the expected healing of the intestinal mucosa and the loss of AAT in the stool.


Secondary Outcome Measures:
  • Suppression of levels of pro-inflammatory cytokines by > 50% [ Time Frame: After doses 1, 2, 3, and 6 ] [ Designated as safety issue: No ]
  • Suppression of levels of pro-inflammatory cytokines by > 50% [ Time Frame: At the completion of study treatment ] [ Designated as safety issue: No ]
  • Infections when treating GVHD with alpha 1 anti-trypsin [ Time Frame: Through 30 days after completion of study treatment ] [ Designated as safety issue: No ]
  • Progression of GVHD [ Time Frame: At 4 weeks after starting therapy ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: February 2013
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (GVHD therapy)
Patients receive alpha 1 anti-trypsin IV on days 1, 3, 5, 7, 9, and 11. Patients not achieving target alpha 1 anti-trypsin concentrations may receive an infusion every 24 hours. Patients with GVHD after 6 infusions may continue treatment for up to 12 infusions.
 Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Biological: alpha 1 antitrypsin
Given IV
Other Name: AAT

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine the optimum dosing parameters of AAT (alpha 1 anti-trypsin) in patients with steroid refractory acute GVHD.

II. Determine clinical toxicity. III. Characterize pharmacodynamic effects of AAT on pro-inflammatory cytokines, heparan sulfate, and the spectrum of peripheral blood T cells.

OUTLINE:

Patients receive alpha 1 anti-trypsin intravenously (IV) on days 1, 3, 5, 7, 9, and 11. Patients not achieving target alpha 1 anti-trypsin concentrations may receive an infusion every 24 hours. Patients with GVHD after 6 infusions may continue treatment for up to 12 infusions.

After completion of study treatment, patients are followed up periodically.

  Eligibility

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
  • Any source of hematopoietic stem cells is allowed
  • Patients may have received any GVHD prophylactic regimen, but developed acute GVHD grades II-IV
  • Patients will have received primary therapy with steroids, but showed progression of or did not resolve clinical manifestations of GVHD on methylprednisolone doses >= 1mg/kg; criteria and indications for secondary systemic therapy of acute GVHD have not been systematically defined; according to American Society for Blood and Marrow Transplantation (ASBMT) guidelines, both severity and duration of manifestations of GVHD will be taken into consideration when deciding that steroid treatment has not adequately controlled GVHD; in general, the decision to initiate secondary therapy will be made sooner for patients with more severe GVHD; for example, secondary therapy may be indicated after 3 days with progressive manifestations of GVHD, after 1 week with persistent, unimproving grade III GVHD or after 2 weeks with persistent, unimproving grade II GVHD; secondary systemic therapy may also be indicated earlier in patients who cannot tolerate high-dose glucocorticoid treatment

Exclusion Criteria:

  • Patients who have received agents in addition to steroids for therapy of GVHD
  • Unable to give informed consent
  • Patients with manifestations of classic chronic GVHD
  • Patients with evidence of recurrent malignancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01523821

Sponsors and Collaborators
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: H. Joachim Deeg Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Deeg, H. Joachim, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT01523821     History of Changes
Other Study ID Numbers: 2571.00, NCI-2011-03805, P01HL036444
Study First Received: January 23, 2012
Last Updated: December 17, 2012
Health Authority: United States: Federal Government

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

ClinicalTrials.gov processed this record on May 16, 2013