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

NCT03459040 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: GCO 17-2666P01CA039542
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (1)

• Number of High Risk Patients Who Develop Steroid Refractory GVHD

  Number of High Risk patients who develop steroid refractory GVHD by day 100 post Hematopoietic cell transplant (HCT) . Steroid refractory GVHD defined as patients who did not achieve Complete Response (CR) or Partial Response (PR) by day 28 of systemic steroid treatment OR if additional immunosuppression beyond steroids was given for treatment of GVHD prior to 28 days of steroid treatment. * CR: All evaluable organs (skin, liver, GI tract) stage 0. For a response to be scored as CR on day 28, the patient must be in CR on that day and have had no intervening additional GVHD therapy. * PR: An improvement in one or more organ involved with GVHD symptoms without worsening in others. For a response to be scored as PR on day 28, the patient must be in PR on that day and have had no intervening additional GVHD therapy.

  Day 100 post HCT.

Secondary Outcomes (8)

• Number of Participants Alive at 6 Months and 1 Year

  6 months and 1 year

• Number of Participants With Non-relapse Mortality (NRM)

  6 months and 1 year

• Number of Participants With Relapse

  1 year

• Number of Participants With Clinically Relevant GVHD States Grade II-IV GVHD

  100 days

• Number of Participants Achieving Overall Response

  Day 28

Study Arms (1)

alpha-1-antitrypsin (AAT)

EXPERIMENTAL

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

Drug: Alpha 1-Antitrypsin

Interventions

Alpha 1-Antitrypsin DRUG

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

Also known as: AAT

alpha-1-antitrypsin (AAT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• John Levine: lead
• National Cancer Institute (NCI): collaborator

Study Sites (5)

City of Hope

Duarte, California, 91010, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

• 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.

  PMID: 33351103 RESULT

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

alpha 1-Antitrypsin

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Acute-Phase Proteins; Blood Proteins; Proteins; Alpha-Globulins; Serum Globulins; Globulins

Results Point of Contact

• Title: Dr. John Levine
• Organization: Icahn School of Medicine at Mount Sinai

john.levine@mssm.edu

212-241-6021

Study Officials

• John Levine, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Internal Medicine and Pediatrics

Model Details: Open label single arm

Study Record Dates

• First Submitted: March 2, 2018
• First Posted: March 8, 2018
• Study Start: August 17, 2018
• Primary Completion: August 21, 2020
• Study Completion: August 21, 2020
• Last Updated: July 12, 2021
• Results First Posted: May 24, 2021

Record last verified: 2021-06

Locations

US (5)