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NCT Number: NCT01523821

Alpha 1 Anti-Trypsin (AAT) in Treating Patients With Acute Graft-Versus-Host Disease GVHD)

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.

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Key information

Conditions

Graft-Versus-Host Disease (GVHD) Acute on Chronic Graft vs Host Disease Immune System Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

About this study

PRIMARY OBJECTIVES:

I. 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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 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

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, 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

Treatment and study plan

Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia]

Drug

Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia] at various levels over different days

Primary outcomes

  1. 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).

Secondary outcomes

  1. 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).

    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.

  2. 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

    Serious adverse reactions were assessed by the NCI CTCAE v4.0.

  3. 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.

    Events were assessed using the NCI CTCAE v4.0.

  4. 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.

    Infections were assessed using NCI CTCAE v4.0.

  5. 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.

    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.

Sponsors and collaborators

Lead sponsor

Fred Hutchinson Cancer Center

Other

Collaborators

  • National Cancer Institute (NCI)
  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study title

Treatment of Steroid Non-responsive Acute GVHD With Alpha 1 Antitrypsin (AAT). A Phase I/II Study

Important dates

Study start
2013
Primary completion
2017
Study completion
2017
First posted
Feb 1, 2012
Registry last updated
Oct 30, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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