Recruiting
Phase 1

CD200AR-L & Tumor Lysate Vaccine

Sponsor:

OX2 Therapeutics

Code:

NCT06305910

Conditions

Diffuse Midline Glioma, H3 K27M-Mutant

Recurrent High Grade Glioma

Eligibility Criteria

Sex: All

Age: 2 - 25

Healthy Volunteers: Not accepted

Interventions

Treatment with CD200AR-L

Study Details

Brief 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).

Conditions

Diffuse Midline Glioma, H3 K27M-Mutant

Recurrent High Grade Glioma

Study ID

NCT06305910

Start date

Mar 15, 2024

Status verified date

Mar, 2024

Completion date

Jan 15, 2027

Anticipated

Primary completion date

Sep 15, 2025

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 2 - 25

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

24 participants

Anticipated

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: CD200AR-L

Up to 3 dose levels (2.0, 3.75, and 5.0 micrograms/kg/dose) of CD200AR-L will be tested with a Dose Level -1 (1.0 microgram/kg/dose) in the event of toxicity at the 2.0 micrograms/kg/dose level. This will be given with fixed doses of 1mg GBM6-AD vaccine and topical imiquimod. A single dose of 300cGy re-irradiation will be given on Day 15. Patients with DMG/DIPG must have completed standard-of-care radiation before enrolling.

The MTD will be identified using the standard 3+3 design. Upon determination of the MTD, additional patients will be enrolled as part of an expansion cohort. This study will first enroll patients ≥ 12 years of age into Dose Level 1 in order to acquire safety data prior to subsequent enrollment of study subjects aged 2-11 years.

Interventions

Treatment 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.

Primary outcome measure

  • Maximum Tolerated Dose (MTD) of CD200AR-L [ Time Frame: 24 months ]

Central Contacts and Locations

Central contacts

Anne Bendel, MD

(612) 813-5940anne.bendel@childrensmn.org

Maggie Skrypek, MD

(612) 813-5940maggie.skrypek@childrensmn.org

Locations

Children's Minnesota

Recruiting

Minneapolis, Minnesota, United States, 55404

Contacts

Anne Bendel, MD

612-813-5940anne.bendel@childrensmn.org

More Information

Sponsor

OX2 Therapeutics

Last update posted

Mar 12, 2024

Last verified

Mar, 2024

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by OX2 Therapeutics on 2024-03-12.