A Study of AbGn-168H in Patients With Steroid Refractory Acute Graft-vs-Host Disease After Donor Stem Cell Transplant

A Phase Ib Treatment Trial Using AbGn-168H to Treat Steroid Refractory Acute Graft-vs.-Host Disease (aGVHD) in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation

This study is to establish the safety, determine if there is an improvement in steroid refractory acute graft-vs-host disease (aGvHD) compared to historical cohorts, and determine the changes of aGvHD-associated T-cell clones in patients with steroid-refractory aGVHD following allogeneic hematopoietic cell transplantation administered AbGn-168H once weekly for 4 weeks.

Study Overview

• Status: Terminated
• Conditions: Acute Graft Versus Host Disease
• Intervention / Treatment: Biological: AbGn-168H

Detailed Description

AbGn-168H is a humanized monoclonal antibody. This is a dose escalation study using a modified toxicity probability interval method. AbGn-168H will be administered intravenously (IV) once weekly for four weeks, in patients with steroid refractory aGVHD following hematopoietic cell transplant (HCT). After completion of study treatment, patients are followed up for 90 days.The primary objective of this study is to establish the safety, and the secondary objectives of this study are to determine if there is an improvement in disease response at 3 months after diagnosis of steroid refractory aGVHD compared to historical cohorts and to determine the changes in frequency and/or phenotype of aGVHD-associated T cell clones in response to AbGn-168H therapy.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University, School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of skin, gut and/or liver steroid-refractory GVHD by clinical assessment of treating physician following allogeneic HCT. Patients who fail to respond to steroids by 7 days are considered steroid-refractory
2. Previously-treated with any conditioning regimen and any GVHD immune suppression prophylaxis and formulation of steroids, except as noted in Exclusion Criteria #2.
3. AbGn-168H (neihulizumab) therapy can begin not more than 14 days after diagnosis of aGvHD
4. Karnofsky Performance Status (KPS) > 50%
5. No evidence of HCT graft failure or multi-organ failure
6. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Uncontrolled infections not responsive to antimicrobial therapy requiring intensive critical care
2. Progressive malignant disease, including post-transplant lymphoproliferative disease unresponsive to therapy
3. Treatment with investigational GVHD prophylactic agents (eg, CCR5 inhibitors; lenalidomide; and/or bortezomib) within the 7 days prior to the 1st dose of neihulizumab
4. Treatment with other investigational agents within the prior 7 days prior to the 1st dose of AbGn-168H (neihulizumab)
5. CMV PCR > 500 copies/mL or evidence of end-organ damage due to CMV
6. Pregnant or nursing
7. HIV positivity (NOTE: patients positive for hepatitis B or hepatitis C are not excluded, and may be evaluated on a case-by-case basis)
8. Renal clearance CCR < 40 mL/min

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AbGn-168H; AbGn-168H will be administered once weekly for four weeks via intravenous infusion.	Biological: AbGn-168H; Humanized monoclonal antibody; Other Names: Neihulizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Grade 3 to 5 adverse events considered at least possibly-related to neihulizumab	On or before study day 52
Cytokine release syndrome or acute infusion reactions	Grade 3 to 5 cytokine release syndrome or acute infusion reactions	Within 24 hours after study drug infusion
Neutropenia	Grade 4 neutropenia lasting more than 14 days considered at least possibly related to study drug	Duration of study
All-cause mortality	Grade 5 all-cause mortality	Within 7 days of infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in frequency and/or phenotype of aGVHD-associated T-cell clones	Changes in T cell clonal dynamics will be accomplished by statistical methodology.	At time of diagnosis up to 90 days
GVHD treatment response as measured by the Modified Keystone aGVHD clinical grade scale	Treatment response will be estimated by the Kaplan Meier product limit method, with standard confidence limits	At 90 days after the diagnosis of aGVHD

Collaborators and Investigators

• Sponsor: AbGenomics B.V Taiwan Branch
• Investigators: Study Director: Shih-Yao (David) Lin, MD, PhD, AbGenomics B.V.; Principal Investigator: Everett Meyer, MD, Stanford University Hospitals and Clinics

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: May 1, 2015
• First Submitted That Met QC Criteria: May 1, 2015
• First Posted (Estimate): May 6, 2015

Study Record Updates

• Last Update Posted (Actual): March 30, 2017
• Last Update Submitted That Met QC Criteria: March 28, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Graft vs Host Disease
• Other Study ID Numbers: BMT 285 (Other Identifier: Stanford University Hospitals and Clinics); 348; NCI-2015-00631 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); IRB-32842

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO