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

Acute Graft Versus Host Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02436460
• Other study ID #: BMT 285
• Secondary ID: NCI-2015-00631IR
• Status: Terminated
• Phase: Phase 1
• First received: May 1, 2015
• Last updated: March 28, 2017
• Start date: May 2015
• Est. completion date: March 2016

Study information

• Verified date: March 2017
• Source: AbGenomics B.V Taiwan Branch
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: March 2016
• Est. primary completion date: March 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Graft Versus Host Disease
• Graft vs Host Disease

Intervention

Biological:
• AbGn-168H
Humanized monoclonal antibody

Locations

Country	Name	City	State
United States	Stanford University, School of Medicine	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
AbGenomics B.V Taiwan Branch

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Grade 3 to 5 adverse events considered at least possibly-related to neihulizumab	On or before study day 52
Primary	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
Primary	Neutropenia	Grade 4 neutropenia lasting more than 14 days considered at least possibly related to study drug	Duration of study
Primary	All-cause mortality	Grade 5 all-cause mortality	Within 7 days of infusion
Secondary	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
Secondary	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