Acute Graft Versus Host Disease
Conditions
Brief 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.
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.
Interventions
BIOLOGICALAbGn-168H
Humanized monoclonal antibody
Sponsors
AbGenomics B.V Taiwan Branch
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | On or before study day 52 | Grade 3 to 5 adverse events considered at least possibly-related to neihulizumab |
| Cytokine release syndrome or acute infusion reactions | Within 24 hours after study drug infusion | Grade 3 to 5 cytokine release syndrome or acute infusion reactions |
| Neutropenia | Duration of study | Grade 4 neutropenia lasting more than 14 days considered at least possibly related to study drug |
| All-cause mortality | Within 7 days of infusion | Grade 5 all-cause mortality |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in frequency and/or phenotype of aGVHD-associated T-cell clones | At time of diagnosis up to 90 days | Changes in T cell clonal dynamics will be accomplished by statistical methodology. |
| GVHD treatment response as measured by the Modified Keystone aGVHD clinical grade scale | At 90 days after the diagnosis of aGVHD | Treatment response will be estimated by the Kaplan Meier product limit method, with standard confidence limits |
Countries
United States
Outcome results
None listed