NCT04144036

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
12

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Dec 2020

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 28, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 30, 2019

Completed
1.1 years until next milestone

Study Start

First participant enrolled

December 14, 2020

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 20, 2023

Completed
1.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 7, 2024

Completed
Last Updated

October 1, 2024

Status Verified

September 1, 2024

Enrollment Period

2.3 years

First QC Date

October 28, 2019

Last Update Submit

September 27, 2024

Conditions

Graft-versus-host Disease

Keywords

Graft-versus-host diseaseNeihulizumab

Outcome Measures

Primary Outcomes (1)

  • Maximum-tolerated dose.

    The maximum-tolerated dose will be defined as the highest dose level at which no more than one of six treated patients, experiences a dose-limiting toxicity.

    Up to 28 days

Secondary Outcomes (4)

  • Treatment response: Complete response

    Day 28

  • Treatment response: Partial response

    Day 28

  • Use of High Dose Steroids

    Day 28

  • Non-relapse mortality.

    6 months

Study Arms (4)

Neihulizumab Dose Escalation, 3 mg/kg

EXPERIMENTAL

Initial dose will be 6 mg weekly and the highest dose administered will be 9 mg weekly. Patients will be entered sequentially to each dose level. If 0 of the first 3 patients at that level has a DLT, new patients may be entered at the next higher dose level. If 1 of 3 patients has a DLT, up to 3 more patients are to be treated at that same dose level. If 0 of the additional 3 patients at that dose level has a DLT, new patients may be entered at the next higher dose level. If 1 or more of the additional 3 patients experience a DLT, 0 patients are to be started at that dose level and the preceding dose is the MTD. If 2 of 3 of the dosed patients has a DLT on the first dose level, the drug will be administered at a lower dose, 3 mg weekly. If 0 of 3 patients has a 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 is the highest dose level at which no more than 1 of 6 treated patients, experiences a DLT.

Biological: Neihulizumab, 3 mg/kg

Neihulizumab Dose Escalation, 6 mg/kg

EXPERIMENTAL

Initial dose will be 6 mg weekly and the highest dose administered will be 9 mg weekly. Patients will be entered sequentially to each dose level. If 0 of the first 3 patients at that level has a DLT, new patients may be entered at the next higher dose level. If 1 of 3 patients has a DLT, up to 3 more patients are to be treated at that same dose level. If 0 of the additional 3 patients at that dose level has a DLT, new patients may be entered at the next higher dose level. If 1 or more of the additional 3 patients experience a DLT, 0 patients are to be started at that dose level and the preceding dose is the MTD. If 2 of 3 of the dosed patients has a DLT on the first dose level, the drug will be administered at a lower dose, 3 mg weekly. If 0 of 3 patients has a 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 is the highest dose level at which no more than 1 of 6 treated patients, experiences a DLT.

Drug: Neihulizumab, 6 mg/kg

Neihulizumab Dose Escalation, 9 mg/kg

EXPERIMENTAL

Initial dose will be 6 mg weekly and the highest dose administered will be 9 mg weekly. Patients will be entered sequentially to each dose level. If 0 of the first 3 patients at that level has a DLT, new patients may be entered at the next higher dose level. If 1 of 3 patients has a DLT, up to 3 more patients are to be treated at that same dose level. If 0 of the additional 3 patients at that dose level has a DLT, new patients may be entered at the next higher dose level. If 1 or more of the additional 3 patients experience a DLT, 0 patients are to be started at that dose level and the preceding dose is the MTD. If 2 of 3 of the dosed patients has a DLT on the first dose level, the drug will be administered at a lower dose, 3 mg weekly. If 0 of 3 patients has a 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 is the highest dose level at which no more than 1 of 6 treated patients, experiences a DLT.

Drug: Neihulizumab, 9 mg/kg

Neihulizumab Dose Expansion

EXPERIMENTAL

Upon determination of the maximum-tolerated dose, 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.

Drug: Neihulizumab

Interventions

Neihulizumab, 3 mg/kgBIOLOGICAL

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.

Also known as: AbGn 168, AbGn 168H
Neihulizumab Dose Escalation, 3 mg/kg
Neihulizumab, 6 mg/kgDRUG

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.

Also known as: AbGn 168, AbGn 168H
Neihulizumab Dose Escalation, 6 mg/kg
Neihulizumab, 9 mg/kgDRUG

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.

Also known as: AbGn 168, AbGn 168H
Neihulizumab Dose Escalation, 9 mg/kg
NeihulizumabDRUG

This arm will receive the Maximum Tolerated Dose determined in the Drug Escalation phase.

Also known as: AbGn 168, AbGn 168H
Neihulizumab Dose Expansion

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients aged ≥ 18 years.
  • Recipients of myeloablative and non-myeloablative, reduced-intensity conditioning allogeneic transplants.
  • Recipients of all donor sources, including sibling, unrelated donor, human leukocyte antigen (HLA) -haploidentical, and HLA-mismatched donors.
  • Patients must have initial presentation of standard-risk aGVHD according to refined Minnesota Criteria. Standard-risk aGVHD is defined as follows:
  • Single organ involvement:
  • Stage 1-3 skin
  • Stage 1 upper GI
  • Stage 1-2 lower GI
  • Multiple organ involvement:
  • Stage 1-3 skin plus stage 1 upper GI
  • Stage 1-3 skin plus stage 1 lower GI
  • Stage 1-3 skin plus stage 1 lower GI plus stage 1 upper GI
  • Stage 1-3 skin plus stage 1-4 liver
  • Stage 1 lower GI plus stage 1 upper GI
  • Patients must not have received prior systemic immune suppressive therapy for the treatment of active aGVHD (topical steroids and budesonide are permitted).
  • +9 more criteria

You may not qualify if:

  • Relapse of disease which was the primary indication for transplant.
  • Uncontrolled infections not responding to antimicrobial therapy.
  • Active and uncontrolled human immunodeficiency virus (HIV), or chronic Hepatitis B, or Hepatitis C.
  • Tuberculosis, history of tuberculosis or a known positive Quantiferon test.
  • Liver dysfunction not attributable to aGVHD evidenced by a Total Bilirubin ≥ 2 x upper limit of normal (ULN).
  • Creatinine clearance \< 40 mL/min calculated by Cockcroft-Gault equation.
  • Intestinal obstruction within three days of enrollment.
  • Life expectancy of less than 28 days, or Eastern Cooperative Oncology Group (ECOG) performance status of 4.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Froedtert Hospital and the Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Graft vs Host Disease

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

  • Sameem Abedin, MD

    Medical College of Wisconsin

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

October 28, 2019

First Posted

October 30, 2019

Study Start

December 14, 2020

Primary Completion

April 20, 2023

Study Completion

July 7, 2024

Last Updated

October 1, 2024

Record last verified: 2024-09

Data Sharing

IPD Sharing
Will not share

Locations

US(1)