What side effects are associated with this type of intervention?

Treatments for Graft-versus-Host Disease (GVHD) that are similar to Neihulizumab, such as other monoclonal antibodies targeting T-cells, commonly have side effects including increased risk of infections, infusion-related reactions (fever, chills, rash), and potential organ-specific toxicities like liver enzyme elevation or gastrointestinal disturbances. Long-term use may also lead to complications such as secondary malignancies or bone marrow suppression.

What prior FDA approvals exist?

The FDA has approved several treatments for Graft-versus-Host Disease (GVHD), particularly focusing on immunosuppressive agents and monoclonal antibodies. One notable approval is for the monoclonal antibody, abatacept, which targets T-cell activation and is used for prophylaxis of acute GVHD. Another significant approval is for ruxolitinib, a JAK1/2 inhibitor, for steroid-refractory acute GVHD. Additionally, tocilizumab, an IL-6 receptor antagonist, has been explored for its efficacy in GVHD. These treatments, like Neihulizumab, aim to modulate the immune response to manage and mitigate the effects of GVHD.

What other types of research exist?

Promising alternatives to Neihulizumab for GVHD treatment include: 1) Alemtuzumab, which targets CD52 on T-cells and has been used in various transplantation settings. 2) Basiliximab, an IL-2 receptor antagonist that can reduce T-cell proliferation. 3) Rituximab, targeting CD20 on B-cells, which has shown efficacy in some GVHD cases. 4) Abatacept, a CTLA-4-Ig fusion protein that modulates T-cell activation. These agents have shown potential in clinical trials and may be considered for GVHD treatment in 2024.

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Monoclonal Antibodies

Neihulizumab for Graft-versus-Host Disease

Phase 1

Recruiting

Led By Sameem Abedin, MD

Research Sponsored by Sameem M. Abedin, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients aged ≥ 18 years

Patients must have initial presentation of standard-risk aGVHD according to refined Minnesota Criteria

Must not have

Life expectancy of less than 28 days, or Eastern Cooperative Oncology Group (ECOG) performance status of 4

Relapse of disease which was the primary indication for transplant

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 6 months

Awards & highlights

Summary

This trial tests Neihulizumab, a medication for treating aGVHD in transplant patients. It focuses on finding the safest and most effective dose by adjusting the amount given to patients over time. The goal is to determine how well the medication works and its safety.

Who is the study for?

Adults over 18 who've had an allogeneic transplant for standard-risk acute Graft Versus Host Disease (aGVHD) can join. They must not have used systemic immune suppressants for aGVHD yet, and women of childbearing age need to use two contraception methods or practice abstinence. Exclusions include uncontrolled infections, certain liver dysfunctions, severe health conditions like HIV or tuberculosis.

What is being tested?

The trial is testing different doses of Neihulizumab to find the highest dose patients with aGVHD can tolerate without too many side effects. It's open to those who received any donor source and either myeloablative or non-myeloablative conditioning regimens before their transplant.

What are the potential side effects?

Specific side effects are not listed here but generally could include reactions at the injection site, potential impact on organ function including liver and kidney issues, increased risk of infection due to immune system suppression, and possibly others as determined during the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My first signs of graft-versus-host disease are considered standard-risk.

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I agree to use the specified methods of contraception.

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I have received a bone marrow transplant.

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I have received a transplant from any type of donor.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am mostly bedridden and have a life expectancy of less than 28 days.

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My original disease has returned after my transplant.

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My kidney function, measured by creatinine clearance, is below 40 mL/min.

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I have an infection that isn't getting better with treatment.

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I have had tuberculosis or a positive TB test.

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I have not had a blockage in my intestines in the last three days.

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I do not have active, uncontrolled HIV, Hepatitis B, or Hepatitis C.

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My liver is not working well, but it's not due to acute graft versus host disease.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 6 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~6 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 6 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Maximum-tolerated dose.

Secondary study objectives

Non-relapse mortality.

Treatment response: Complete response

Treatment response: Partial response

+1 more

Trial Design

4Treatment groups

Experimental Treatment

Group I: Neihulizumab Dose ExpansionExperimental Treatment1 Intervention

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.

Group II: Neihulizumab Dose Escalation, 9 mg/kgExperimental Treatment1 Intervention

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.

Group III: Neihulizumab Dose Escalation, 6 mg/kgExperimental Treatment1 Intervention

Group IV: Neihulizumab Dose Escalation, 3 mg/kgExperimental Treatment1 Intervention

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Graft-versus-Host Disease (GVHD) often involve monoclonal antibodies and immunosuppressive agents to modulate the immune response. Neihulizumab, a monoclonal antibody targeting T-cells, aims to reduce the immune-mediated damage by preventing donor T-cells from attacking the recipient's tissues. This is crucial for GVHD patients as it helps to mitigate the severe inflammatory responses that characterize the disease. Other treatments, such as anti-CD20 monoclonal antibodies, target B-cells, while immunosuppressive agents like cyclophosphamide and prednisone broadly suppress the immune system to prevent T-cell activation and proliferation, thereby reducing the risk and severity of GVHD.

Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease.