NCT04144036

Neihulizumab for Standard-Risk Acute Graft Versus Host Disease (GVHD)

A Phase I Trial of Neihulizumab for the Upfront Treatment of Standard-Risk, Ann Arbor Scoring 1-2 Acute Graft vs Host Disease

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Sameem M. Abedin, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a single-center Phase I study to determine the maximum tolerated dose and safety of Neihulizumab for the treatment of Minnesota standard-risk aGVHD. Patients undergoing allogeneic transplant with either a myeloablative or non-myeloablative conditioning regimen, and recipients of all donor sources will be enrolled to this trial.

Detailed description

Eligible patients will receive Neihulizumab weekly, for up to four doses. Responding patients, and patients with stable disease should receive all four weekly doses. Patients with skin only disease that clinically progresses by one stage (e.g, from stage 2 to stage 3), but remains less than stage 4, will receive a minimum two doses of Neihulizumab. At 72 hours after the second dose, non-responding patients will be withdrawn from the study. Responding patients should remain on study and receive four total doses. Patients with lower GI GVHD that progresses by at least one stage at 4 or more days after first dose will be withdrawn from the study. All patients receiving at least 1 dose of Neihulizumab will be evaluated for dose-limiting toxicities (DLTs) and adverse events. Dose-escalation will be conducted according to a 3+3 design. The initial dose of Neihulizumab will be 6 mg/kg weekly (Dose level 1), and the highest dose administered will be 9 mg/kg weekly (Dose level 2). The DLT observation period will be 28 days. Patients will be entered sequentially to each dose level. For each dose level, if none of the first 3 patients at that level experiences a DLT, new patients may be entered at the next higher dose level. If 1 of 3 patients experiences a DLT, up to 3 more patients are to be treated at that same dose level. If none of the additional 3 patients at that dose level experiences a DLT, new patients may be entered at the next higher dose level. However, if 1 or more of the additional 3 patients experience a DLT, then no further patients are to be started at that dose level and the preceding dose is the maximum-tolerated dose (MTD). If 2 of 3 of the initially dosed patients experience a DLT on the first dose level, Neihulizumab will be administered at a lower dose, 3mg/kg weekly (Dose level -1). Finally, if 0 of 3 patients experience DLT at the highest dose level, an additional 3 patients will be enrolled to ensure that 6 patients are treated at the MTD. The MTD will be defined as the highest dose level at which no more than 1 of 6 treated patients, experiences a DLT. Upon determination of MTD, an expansion cohort of 4-7 patients will be enrolled so that a total of 10 patients are enrolled at the potential Phase II dose. This will be done to preliminarily assess efficacy.

Conditions

• Graft-versus-host Disease

Interventions

Type	Name	Description
BIOLOGICAL	Neihulizumab, 3 mg/kg	The doses for the 3 + 3 design (dose escalation phase) are listed in the arm description. The dose-expansion phase will use the maximum-tolerated dose.
DRUG	Neihulizumab, 6 mg/kg	The doses for the 3 + 3 design (dose escalation phase) are listed in the arm description. The dose-expansion phase will use the maximum-tolerated dose.
DRUG	Neihulizumab, 9 mg/kg	The doses for the 3 + 3 design (dose escalation phase) are listed in the arm description. The dose-expansion phase will use the maximum-tolerated dose.
DRUG	Neihulizumab	This arm will receive the Maximum Tolerated Dose determined in the Drug Escalation phase.

Timeline

• Start date: 2020-12-14
• Primary completion: 2023-04-20
• Completion: 2024-07-07
• First posted: 2019-10-30
• Last updated: 2024-10-01

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study