New immunotherapy for treating brain tumors in children and young adults

Phase I Trial: CD200 Activation Receptor Ligand (CD200AR-L) and Allogeneic Tumor Lysate Vaccine Immunotherapy With Adjuvant Reirradiation for Recurrent High-Grade Glioma and Newly Diagnosed Diffuse Midline Glioma/Diffuse Intrinsic Pontine Glioma in Children and Young Adults

This study is testing a new immunotherapy treatment for children and young adults with aggressive brain tumors to see if it can help their immune system fight the cancer better.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 2 Years to 25 Years
• Sex: All
• Sponsor: OX2 Therapeutics (Industry-sponsored)
• Drugs / interventions: bevacizumab, immunotherapy, radiation
• Locations: 1 site (Minneapolis, Minnesota)
• Trial ID: NCT06305910 on ClinicalTrials.gov

What this trial studies

This Phase I clinical trial evaluates the safety and maximum tolerated dose of CD200AR-L, an experimental agent, in combination with the GBM6-AD vaccine and imiquimod cream for treating recurrent High Grade Glioma (HGG) and newly diagnosed Diffuse Midline Glioma/Diffuse Intrinsic Pontine Glioma (DMG/DIPG) in children and young adults. The study aims to overcome immune suppression caused by CD200 secretion from tumor cells, thereby enhancing the immune response against these aggressive brain tumors. Participants will receive a single dose of radiation alongside the immunotherapy regimen to assess its safety and potential effectiveness.

Who should consider this trial

Good fit: Ideal candidates include children and young adults with newly diagnosed DMG/DIPG exhibiting H3K27M mutations or those with recurrent HGG who have previously undergone standard radiation therapy.

Not a fit: Patients with tumors that do not express the H3K27M mutation or those who are not clinically stable may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for children and young adults with aggressive brain tumors, potentially improving survival rates and quality of life.

How similar studies have performed: While this approach is novel in the context of pediatric brain tumors, previous studies with the GBM6-AD vaccine have shown safety, indicating potential for further exploration.

Eligibility criteria

Inclusion Criteria:

* Histologically confirmed newly diagnosed DIPG/DMG with documented H3K27M alteration (based on IHC or DNA sequencing performed in a CLIA-certified laboratory) or recurrent HGG. Patients cannot enroll until they are a minimum of 14 days and preferably within 30 days from the last dose of radiation.
* Diagnosis of recurrent HGG based on MRI findings. Recurrent HGG must have received standard of care radiation at diagnosis. Prior biopsy material will be required to confirm diagnosis of HGG; however, biopsy of the recurrent/progressive lesion will not be required for study enrollment.
* Maximal safe resection is preferred prior to clinical trial enrollment if indicated and feasible.
* Clinically stable on a dose of corticosteroids not to exceed an equivalent of dexamethasone 0.1 mg/kg/day (maximum 4 mg) for at least 2 weeks prior to study enrollment.
* Prior therapy wash-out is required
* Minimum of 28 days since last dose of any targeted therapy (including bevacizumab), immunotherapy, investigational agents.
* Minimum of 10 days since any anti-cancer intervention: cytoreductive surgery/laser ablation and a minimum of 28 days since any viral therapy
* Voluntary written consent obtained by patient if ≥18 years of age or a parent or guardian if \<18 years of age before the performance of any study-related procedure not part of standard medical care
* Able to comply with follow-up visit schedule (i.e., return to clinic for follow-up visits).
* Willing to allow for collection of pre-treatment research related blood collection \[1-5 mL red top tube and 2-10 mL green top tubes (or to a max of 2 ml/kg of body weight)\] for immune characterization. If a patient does not subsequently enroll in the study, the samples will be destroyed according to institutional protocol.
* Lansky play performance score ≥60 (\<16 years) or Karnofsky (≥16 years) performance score of ≥60
* Sexually active persons of child-bearing potential or with partners of childbearing potential must agree to use a highly effective form of contraception during the 2-year treatment period. Urine pregnancy tests will be obtained at defined time points during protocol therapy.
* Adequate bone marrow reserve: Absolute neutrophil (segmented and bands) count (ANC) ≥1.0 x 10E9/L, platelets ≥75 x 10E9/L; Hemoglobin ≥8 g/dL
* Hepatic: Bilirubin ≤1.3 mg/dL and SGPT (ALT) ≤2.5 x upper limit of normal (ULN) for age
* Renal: Normal serum creatinine for age or creatinine clearance \>60 ml/min/1.73 mE2

Exclusion Criteria:

* Known sensitivity to the GBM6-AD tumor lysate vaccine, CD200AR-L, or imiquimod.
* Unable to complete a standard upfront course of radiotherapy due to disease progression or intolerance of therapy.
* Radiographic evidence of diffuse leptomeningeal disease.
* Prior history of malignancy within 5 years of enrollment.
* Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
* Concurrent use of tumor treatment field devices (e.g., Optune) - permitted until the time of consent.
* History of any laboratory findings consistent with any uncontrolled immune system abnormalities such as hyper-immunity (e.g., autoimmune diseases, thyroid dysfunction, lupus, scleroderma, etc.) and hypo-immunity \[e.g., myelodysplastic disorders, marrow failures, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), transplant immune-suppression, etc.\]. Any known autoimmune disease must be clinically silent and without associated laboratory abnormalities for at least 1 year in the absence of any disease directed therapy or systemic steroids.
* Any conditions that could potentially alter immune function (e.g., HIV/AIDS, hepatitis B, untreated hepatitis C, multiple sclerosis, renal failure).
* Receiving ongoing treatment with any immunosuppressive drug for any reason, excluding those patients requiring a low dose of corticosteroids equivalent to dexamethasone 0.1 mg/kg/day (maximum 4 mg) or less for treatment of tumor-related edema.
* Not able to tolerate an MRI or radiation therapy even with reasonable accommodations or sedation.
* Known pregnancy or anticipated conception during the 1-year study period

Where this trial is running

Minneapolis, Minnesota

• Children's Minnesota — Minneapolis, Minnesota, United States (Recruiting)

Study contacts

• Study coordinator: Anne Bendel, MD

Conditions Diffuse Midline Glioma, H3 K27M-Mutant; Recurrent High Grade Glioma