CD200AR-L and Allogeneic Tumor Lysate Vaccine Immunotherapy for Recurrent HGG and Newly Diagnosed DMG/DIPG in Children and Young Adults

Launched by OX2 THERAPEUTICS · Mar 5, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment approach for specific brain tumors in children and young adults, particularly those with recurrent high-grade glioma or newly diagnosed diffuse midline glioma, which includes a type called DIPG. The treatment combines a new substance called CD200AR-L with an existing vaccine and a cream to help the immune system target the tumor better. The main goal of the trial is to find out the highest safe dose of this new treatment when given alongside radiation therapy.

To participate, eligible patients must be diagnosed with certain types of brain tumors that have specific genetic changes, and they should be at least 14 days after their last radiation treatment. Participants will need to be in stable health and able to return for follow-up appointments. During the trial, patients can expect to receive this new treatment along with standard care, and their health will be closely monitored. Parents or guardians will need to give permission for younger participants, and there are certain health criteria that must be met to ensure safety throughout the study.

Gender

ALL

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