Overview

A Proof of Concept Pilot Trial of Alpha-1-Antitrypsin for Pre-Emption Of Steroid-Refractory Acute GVHD

Status:
Completed
Trial end date:
2020-08-21
Target enrollment:
0
Participant gender:
All
Summary
Bone marrow transplant (BMT) patients can develop graft-versus-host disease (GVHD), a serious and potentially fatal complication. The researchers have developed a blood test to identify patients most at risk for developing severe GVHD. Patients who consent to this study will have their blood tested up to two times after BMT to determine if they are at high risk for severe GVHD. The tests will be performed one week and two weeks after BMT. Patients who are high risk will be treated with a drug called alpha-1-antitrypsin (AAT) to see if it prevents the development of severe GVHD. Patients will receive 16 doses of AAT through a catheter placed into a blood vessel over eight weeks. AAT will be given either in the hospital or the outpatient clinic two times per week. Patients will be followed for the development of severe GVHD for up to four months from the BMT and will continue to be followed at routine clinic visits for up to one year after BMT.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
John Levine
Collaborator:
National Cancer Institute (NCI)
Treatments:
Alpha 1-Antitrypsin
Protein C Inhibitor
Criteria
Inclusion Criteria:

- High risk prediction score as determined by the Mount Sinai Acute GVHD International
Consortium (MAGIC) algorithm at either day 7 or day 14 post Hematopoietic cell
transplant (HCT).

- Any donor type (e.g., related, unrelated) or stem cell source (bone marrow, peripheral
blood, cord blood).

- Donor and recipient match each other for at least 7/8 HLA-loci (HLA-A, B, C, and DR)

- Any conditioning regimen (non-myeloablative, myeloablative, or reduced intensity) is
acceptable.

- GVHD prophylaxis must include a calcineurin inhibitor combined with methotrexate or
mycophenolate.

- The use of serotherapy to prevent GVHD (e.g., antithymocyte globulin) prior to day 3
post-HCT is permitted

- Direct bilirubin must be <2 mg/dL unless the elevation is known to be due to Gilbert
syndrome within 3 days prior to enrollment.

- ALT/SGPT and AST/SGOT must be <5 x the upper limit of the normal range within 3 days
prior to enrollment.

- Signed and dated written informed consent obtained from patient or legal
representative.

Exclusion Criteria:

- Patients who develop acute GVHD prior to start of study drug

- Patients at very high risk for relapse post HCT as defined by very high disease risk
index

- Patients participating in a clinical trial where prevention of GVHD is the primary
endpoint

- Uncontrolled active infection (i.e., progressive symptoms related to infection despite
treatment or persistently positive microbiological cultures despite treatment or any
other evidence of severe sepsis)

- Patients who are pregnant

- Patients on dialysis within 7 days of enrollment

- Patients requiring ventilator support or oxygen supplementation exceeding 40% FiO2
within 14 days of enrollment.

- Patients receiving investigational agent within 30 days of enrollment. However, the
Principal Investigator (PI) may approve prior use of an investigational agent if the
agent is not expected to interfere with the safety or the efficacy of
alpha-1-antitrypsin.

- History of allergic reaction to alpha-1-antitrypsin