What side effects are associated with this type of intervention?

Common treatments for neuroblastoma, such as those involving dinutuximab, temozolomide, irinotecan, and zoledronate, can have several side effects. Dinutuximab, an anti-GD2 monoclonal antibody, often causes pain, fever, and allergic reactions. Temozolomide, an oral chemotherapy drug, can lead to nausea, vomiting, fatigue, and myelosuppression. Irinotecan, another chemotherapy agent, frequently results in diarrhea, abdominal pain, and myelosuppression. Zoledronate, used to enhance γδ T cell activation, may cause flu-like symptoms, bone pain, and renal toxicity. Additionally, cell-based immunotherapies like γδ T cells can cause cytokine release syndrome and other immune-related adverse effects.

What prior FDA approvals exist?

The FDA has approved dinutuximab, an anti-GD2 monoclonal antibody, for the treatment of high-risk neuroblastoma. Dinutuximab is used in combination with other agents such as granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), and isotretinoin. This combination has shown to improve survival rates in children with high-risk neuroblastoma. The current trial involving allogeneic γδ T cells aims to enhance the efficacy of such treatments by combining dinutuximab with temozolomide, irinotecan, and zoledronate, which enhances γδ T cell activation and potency.

What other types of research exist?

Promising novel alternatives for Neuroblastoma treatment in 2024 include: 1) Anti-GD2 monoclonal antibodies (e.g., dinutuximab) combined with chemotherapy agents like temozolomide and irinotecan, which have shown robust response rates. 2) CAR-T cell therapies targeting GD2, which are being developed to enhance specificity and efficacy against neuroblastoma cells. 3) Oncolytic virotherapy, which uses genetically modified viruses to selectively infect and kill cancer cells while stimulating an anti-tumor immune response. 4) Immune checkpoint inhibitors (e.g., pembrolizumab) that can enhance the body's immune response against tumor cells.

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Monoclonal Antibodies

Gamma Delta T Cell Immunotherapy + Chemoimmunotherapy for Neuroblastoma (Aflac-NBL-2002 Trial)

Phase 1

Recruiting

Led By Kelly Goldsmith, MD

Research Sponsored by Emory University

Eligibility Criteria Checklist

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

Must have

- Refractory disease: A best overall response of no response/stable disease since diagnosis of high risk neuroblastoma AND after at least 4 courses of high risk neuroblastoma induction therapy.

- Renal Function: Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age.

Must not have

Patients who are on hemodialysis

Patients who have had to permanently discontinue Dinutuximab due to toxicity

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from day 1 of protocol therapy through 30 days following end of protocol therapy

Awards & highlights

Approved for 5 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial tests a new treatment combining existing cancer drugs with special immune cells and a booster drug in children with aggressive neuroblastoma. The goal is to see if this combination can more effectively fight the cancer.

Who is the study for?

This trial is for children over 12 months old with high-risk neuroblastoma that's relapsed or not responded to treatment. They need normal heart, kidney, liver, and bone marrow function and can't have had prior T cell therapy or stem cell transplant. No major organ system diseases, active infections, or uncontrolled cardiac issues are allowed.

What is being tested?

The study tests a new combination of treatments for aggressive childhood cancer: γδ T cells from donors plus standard drugs (dinutuximab, temozolomide, irinotecan) and zoledronate. It aims to find the safest dose and see how well it works in kids with tough-to-treat neuroblastoma.

What are the potential side effects?

Potential side effects include reactions related to immune response due to γδ T cells and dinutuximab infusion; toxicity from chemotherapy agents like temozolomide and irinotecan affecting blood counts; nausea; fatigue; liver impact; as well as risks associated with zoledronate such as bone pain.

Eligibility Criteria

Inclusion Criteria

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

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My neuroblastoma has not improved after 4 treatment cycles.

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My kidney function is within the normal range for my age.

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My liver tests are within the required range.

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I have been diagnosed with neuroblastoma confirmed by tests.

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My neuroblastoma has partially responded after 4+ treatment rounds.

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I don't have trouble breathing at rest or during exercise.

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I am older than 12 months.

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My blood cell counts meet the required levels and I don't need blood transfusions.

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My heart's pumping ability is normal, confirmed by a heart scan.

Exclusion Criteria

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

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I am currently receiving hemodialysis.

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I had to stop taking Dinutuximab because of its side effects.

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I do not have serious, uncontrolled heart rhythm problems.

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I have had myocarditis in the past.

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I have previously undergone T cell therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from day 1 of protocol therapy through 30 days following end of protocol therapy

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from day 1 of protocol therapy through 30 days following end of protocol therapy

This trial's timeline: 3 weeks for screening, Varies for treatment, and from day 1 of protocol therapy through 30 days following end of protocol therapy 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/Recommended Phase 2 Dose of gamma delta T cells

Secondary study objectives

Describe Hematological Toxicities

Describe Non-Hematological Toxicities

Overall Response

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Dose Escalation Phase I cohortExperimental Treatment1 Intervention

Subjects will be assigned a cell therapy dose level at time of registration. The entry dose level is Dose Level 1, with escalation up to Dose Level 3 following a 3 + 3 dose escalation design. If there is no evidence of progression, patients may receive up to a maximum of 4 courses. Each course includes two administrations of γδ T cells, administered one week apart. Toxicity, for deciding dose escalation and defining the MTD, will be evaluated during Course 1. Disease response assessment will be done after Courses 2 and 4. Dinutuximab (17.5 mg/m2), temozolomide (100 mg/m2), irinotecan (50 mg/m2) and zoledronate (0.0125 mg/kg/dose) will be consistent across all dose levels.The same donor for γδ T cell will be used for both cell therapy product infusions per course. Treatment of the first two subjects in each dose escalation cohort will be staggered. The second subject will not be enrolled until the first subject completes the DLT observation interval (minimum of 21 days).

0 / 14Eligibility 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

The most common treatments for neuroblastoma, particularly those involving allogeneic γδ T cells, work through several mechanisms. γδ T cells exhibit direct cytotoxicity to tumor cells without the need for major histocompatibility complex (MHC) recognition, allowing them to target a broad range of tumor cells. This MHC-independence is crucial as it bypasses the tumor's ability to evade immune detection. Additionally, the efficacy of γδ T cells is enhanced by zoledronate, which boosts their activation and potency. Chemoimmunotherapy, combining agents like dinutuximab with chemotherapy drugs such as temozolomide and irinotecan, further augments the immune response against neuroblastoma. These mechanisms are significant for neuroblastoma patients as they offer a robust and targeted approach to treatment, potentially improving survival rates and reducing the likelihood of relapse.