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
OX2 Therapeutics
Summary
This is a single center Phase I study of a new adjuvant CD200 activation receptor ligand, CD200AR-L, in combination with imiquimod and GBM6-AD vaccine to treat malignant glioma in children and young adults. The primary objective of this study is to determine the maximum tolerated dose (MTD) of CD200AR-L when given with a fixed dose of GBM6-AD vaccine, imiquimod, and a single dose of radiation for patients with recurrent High Grade Glioma (HGG) or following standard of care therapy radiation therapy for newly diagnosed Newly Diagnosed Diffuse Midline Glioma/Diffuse Intrinsic Pontine Glioma (DIPG/DMG).
Description
A previous pediatric trial using GBM6-AD vaccine was found to be safe, and an appropriate pediatric dose of GBM6-AD was determined, but the efficacy of the vaccine was diminished due to secretion of CD200 by the patient's HGG or DMG/DIPG cells. CD200 is known to binds to CD200 inhibitory receptor (CD200R1) on immune cells and suppress the immune cell response. Laboratory studies have shown that administering agents that bind to the CD200 activation receptor (CD200-AR) on immune cells results in activation of immune cells and overcomes any inhibitory signals caused by CD200. CD200AR-L is a new…
Eligibility
- Age range
- 2–25 years
- Sex
- All
- Healthy volunteers
- No
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 en…
Interventions
- DrugTreatment with CD200AR-L
Treatment with CD200AR-L (up to 3 dose levels of CD200AR-L with a Dose Level -1 in the event of toxicity) with fixed doses of GBM6-AD vaccine. Each patient will also be given topical imiquimod and a single dose of 300cGy re-irradiation.
Location
- Children's MinnesotaMinneapolis, Minnesota