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

Status:	Recruiting
Conditions:	Hematology
Therapuetic Areas:	Hematology
Healthy:	No
Age Range:	18 - 75
Updated:	9/2/2018
Start Date:	August 17, 2018
End Date:	February 26, 2020
Contact:	Artur Shchukin
Email:	artur.shchukin@mssm.edu
Phone:	212-241-0497

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.

Inclusion Criteria:

- High risk prediction score as determined by the MAGIC algorithm at either day 7 or day
14 post 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

We found this trial at

sites

City of Hope

Duarte, California 91010

Principal Investigator: Ryotaro Nakamura, MD

Phone: 626-256-4673

from

Duarte, CA