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.

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.

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