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

NCT ID: NCT03459040

Last Updated: 2021-07-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-17
• Study Completion Date: 2020-08-21

Brief 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.

Conditions

Graft-versus-host-disease; GVHD

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

alpha-1-antitrypsin (AAT)

16 doses of AAT through a catheter placed into a blood vessel over eight weeks.

Group Type: EXPERIMENTAL

Alpha 1-Antitrypsin

Intervention Type: DRUG

AAT will be given either in the hospital or the outpatient clinic two times per week.

Interventions

Alpha 1-Antitrypsin

AAT will be given either in the hospital or the outpatient clinic two times per week.

Intervention Type: DRUG

Other Intervention Names

AAT

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

John Levine

OTHER

Sponsor Role: lead

Responsible Party

John Levine

Professor of Internal Medicine and Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John Levine, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

City of Hope

Duarte, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Ohio State University

Columbus, Ohio, United States

Vanderbilt University

Nashville, Tennessee, United States

Countries

United States

References

Gergoudis SC, DeFilipp Z, Ozbek U, Sandhu KS, Etra AM, Choe HK, Kitko CL, Ayuk F, Aziz M, Baez J, Ben-David K, Bunworasate U, Gandhi I, Hexner EO, Hogan WJ, Holler E, Kasikis S, Kowalyk SM, Lin JY, Merli P, Morales G, Nakamura R, Reshef R, Rosler W, Srinagesh H, Young R, Chen YB, Ferrara JLM, Levine JE. Biomarker-guided preemption of steroid-refractory graft-versus-host disease with alpha-1-antitrypsin. Blood Adv. 2020 Dec 22;4(24):6098-6105. doi: 10.1182/bloodadvances.2020003336.

Reference Type: RESULT

PMID: 33351103 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P01CA039542

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GCO 17-2666

Identifier Type: -

Identifier Source: org_study_id