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

NCT06305910 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CMN-DMGVac-01
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of CD200AR-L

  Maximum tolerated dose (MTD) of CD200AR-L when administered with imiquimod and GBM6-AD vaccine to treat High-Grade Glioma (HGG) and Newly Diagnosed Diffuse Midline Glioma/Diffuse Intrinsic Pontine Glioma (DMG/DIPG) in children and young adults.

  24 months

Secondary Outcomes (4)

• Incidence of serious adverse events (SAEs)

  24 months

• Time to progression (TTP) by 24 months

  24 months

• Progression free survival (PFS) by 24 months

  24 months

• Overall survival (OS) by 24 months

  24 months

Study Arms (1)

CD200AR-L

EXPERIMENTAL

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.

Drug: Treatment with CD200AR-L

Interventions

Treatment with CD200AR-L DRUG

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.

Also known as: Imiquimod, GBM6-AD, Single dose of radiation (300 cGy)

CD200AR-L

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• OX2 Therapeutics: lead

Study Sites (1)

Children's Minnesota

Minneapolis, Minnesota, 55404, United States

RECRUITING

MeSH Terms

Conditions

Glioma

Interventions

Therapeutics; Imiquimod; Radiation

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Physical Phenomena

Central Study Contacts

Anne Bendel, MD

CONTACT

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

Maggie Skrypek, MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 3+3 design

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: March 12, 2024
• Study Start: March 15, 2024
• Primary Completion: September 15, 2025
• Study Completion (Estimated): January 15, 2027
• Last Updated: March 12, 2024

Record last verified: 2024-03

Locations

US (1)