Clinical trial
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
Name
CMN-DMGVac-01
Description
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).
Trial arms
Trial start
2024-03-15
Estimated PCD
2025-09-15
Trial end
2027-01-15
Status
Recruiting
Phase
Early phase I
Treatment
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.
Arms:
CD200AR-L
Other names:
Imiquimod, GBM6-AD, Single dose of radiation (300 cGy)
Size
24
Primary endpoint
Maximum Tolerated Dose (MTD) of CD200AR-L
24 months
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
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': '3+3 design', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 24, 'type': 'ESTIMATED'}}
Updated at
2024-03-12
1 organization
1 product
3 indications
Organization
OX2 TherapeuticsProduct
CD200AR-LIndication
Diffuse Midline GliomaIndication
H3 K27M-MutantIndication
Recurrent High Grade Glioma