Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial Summary
A Phase I study to establish the pharmacokinetics, pharmacodynamics, safety and efficacy
profiles of Neihulizumab in patients with steroid-refractory or treatment refractory acute
graft-versus-host disease (SR/TR-aGVHD)
Phase
Phase 1
Funding Agency/Sponsor
Industrial
Disease
Lymphoma
Enrollment Eligibility
Inclusion Criteria (must meet all of the following criteria):
1. Patients must have clinical aGVHD and pathologic findings consistent with the
diagnosis by biopsy of at least 1 involved site, and
1. progressed after 3 days of treatment with methylprednisolone (MP) 2 mg/kg/day
equivalent, or
2. did not improve after 7 days of treatment with MP 2 mg/kg/day equivalent, or
3. progressed to involve a new organ after treatment with MP 1 mg/kg/day equivalent
for skin and upper gastrointestinal (GI) GVHD, or
4. recurred during or after a steroid taper
2. For single dose phase: Patients must have erythematous manifestations of cutaneous
aGVHD. Characteristics of the rash must indicate active inflammation (red coloration)
as distinct from resolving inflammation (brown coloration).
3. For single dose phase: Providers and patients must be willing to defer new systemic or
cutaneous topical treatment of aGVHD for at least 36 hr after administration of
Neihulizumab.
4. Patient must give informed consent and sign an approved consent form prior to any
study procedures.
5. Females of childbearing potential must have a negative pregnancy test result before
enrollment. Males and females of childbearing potential must agree to use a highly
effective method of birth control during the study for at least 30 days after
enrollment in the study.
Exclusion Criteria (may not meet any of the following criteria):
1. For single dose phase: Prior administration of anti-lymphocyte globulin or anti-
thymocyte globulin for treatment of aGVHD.
2. For multiple dose phase: Has received any systemic treatment in addition to
corticosteroids for aGVHD.
3. Stage 4 lower GI GVHD, defined by the presence of ileus, severe abdominal pain, or
overt GI bleeding.
4. Uncontrolled infections not responding to antimicrobial therapy or requiring intensive
critical care or vasopressors.
5. Evidence of end-organ cytomegalovirus (CMV) or adenovirus infection.
6. Known to have adenovirus, or Epstein Barr virus (EBV) viremia from screening according
to institutional standard practice. Patients receiving appropriate antiviral treatment
for CMV, HHV6 or hepatitis viremia are eligible on a case-by-case basis.
7. HIV infection or a known HIV-related malignancy.
8. Tuberculosis, history of tuberculosis or a known positive Quantiferon test for
tuberculosis.
9. Unplanned donor lymphocyte infusion (DLI) for residual or relapsed malignancy or mixed
chimerism. DLI as part of the planned HCT protocol is allowed.
10. Known relapsed or progressive malignancy after transplant, posttransplant
lymphoproliferative disease or any secondary malignancy diagnosed after HCT.
11. Absolute neutrophil count (ANC) <1000/mm3.
12. Total serum bilirubin concentration >3.0 mg/dL UNLESS attributed to GVHD.
13. Creatinine clearance < 30 mL/min calculated by Cockcroft-Gault equation.
14. Sodium (Na) concentration < 130 mmol/L.
15. Karnofsky Performance Status (KPS) or Lansky Performance Status < 20%.
16. Intensive care unit (ICU) care, life expectancy of less than 28 days, ongoing or
unresolved hepatic sinusoidal obstruction syndrome, unstable hemodynamics, or evidence
of current or previous clinically significant disease, medical condition or finding
(including vital signs and ECG) that in the opinion of the Investigator, would
compromise the safety of the patient or the quality of the data.
17. History of allergy or hypersensitivity to any systemically administered antibody agent
or its excipients.
18. Pregnancy or nursing.
19. Less than 12 years of age.