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

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Graft-Versus-Host Disease (GVHD) Acute on Chronic

Treatments: Drug: Alpha 1-Proteinase Inhibitor, Human 1 MG [Glassia]

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01523821

P01HL036444 (U.S. NIH Grant/Contract)

2571

NCI-2011-03805 (Registry Identifier)

2571.00 (Other Identifier)

P30CA015704 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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20 participants in 3 patient groups

Cohort 1 (30 mg/kg)

Other group

Description:

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.

Treatment:

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

Cohort 2 (60 mg/kg)

Other group

Description:

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.

Treatment:

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

Cohort 3 (90 mg/kg)

Other group

Description:

AAT will be administered intravenously at a dose of 90 mg/kg on days 1, 3, 5, 7, 9, 11, 13 \& 15.

Treatment:

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