Neihulizumab in Treating Patients With Steroid Refractory Acute Graft-versus-Host Disease After Donor Stem Cell Transplant

PRIMARY OBJECTIVES:

I. To establish the safety of administering AbGn-168H (neihulizumab) in patients with
steroid refractory aGVHD following hematopoietic cell transplant (HCT).

SECONDARY OBJECTIVES:

I. To determine if there is an improvement in disease response at 3 months after diagnosis
of steroid refractory aGVHD compared to historical cohorts.

II. To determine the changes in frequency and/or phenotype of aGVHD-associated T cell clones
in response to AbGn-168H therapy.

OUTLINE: This is a dose-escalation study.

Patients receive neihulizumab intravenously (IV) on days 1, 8, 15, and 22.

After completion of study treatment, patients are followed up for 90 days.

Inclusion Criteria:

- Patients with a diagnosis of skin, gut and/or liver steroid refractory GVHD by
clinical assessment of treating physician following allogeneic HCT

- Patients can be treated with any conditioning regimen and any GVHD immune suppression
prophylaxis and formulation of steroids

- Karnofsky performance status > 50

- No evidence of HCT graft failure or multi-organ failure

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Uncontrolled infections not responsive to antimicrobial therapy requiring intensive
critical care

- Progressive malignant disease, including post transplant lymphoproliferative disease
unresponsive to therapy

- Patients previously treated on prophylactic aGVHD prevention clinical trials with
ongoing prophylactic agents such as C-C chemokine receptor type 5 (CCR5) inhibitors,
lenalidomide and bortezomib will be excluded

- Cytomegalovirus (CMV) polymerase chain reaction (PCR) > 500 or evidence of end-organ
damage due to CMV

- Pregnant or nursing patients are excluded from allogeneic HCT at Stanford and from
this study

- Human immunodeficiency virus (HIV) positivity; (patients positive for hepatitis B or
hepatitis C are not excluded, and may be evaluated on a case-by-case basis)

- Patients with a renal clearance creatinine clearance rate (CCR) < 40 ml/min