Intrathecal Azacitidine and Nivolumab in Patients With Recurrent High-grade Glioma

Enrolling by invitation · Phase 1

Conditions studied: Glioblastoma (GBM), Diffuse Midline Glioma (DMG), Astrocytoma, IDH-Mutant, Grade 4, Diffuse Hemispheric Glioma, H3 G34-Mutant, Gliosarcoma of Brain

In brief

This is a single-arm open-label phase 1 dose escalation/expansion trial assessing the safety and efficacy of concurrent intrathecal azacitidine and intrathecal nivolumab in recurrent high-grade glioma.

Key facts

Study ID: NCT06896110
Run by: Andrew P. Groves
People needed: 34
Starts: 2025-06-05
Expected to finish: 2027-03-01
Last updated by the study team: 2025-06-26

Who can join

Age: 13 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

For patients age ≥ 18: Able and willing to provide written informed consent
For patients aged 13-17: Parent/guardian of adolescent patient must have the ability to provide written informed consent. Adolescent patients must have the ability to provide written informed assent.
Stated willingness to comply with all trial procedures and availability for the duration of the trial
Histologically confirmed diagnosis of World Health Organization Grade IV high-grade glioma. Eligible diagnoses include: Glioblastoma (IDH-wildtype), Gliosarcoma, Diffuse Midline Glioma (H3 K27-altered), diffuse hemispheric glioma (H3 G34-mutant), diffuse pediatric-type high-grade glioma (H3 and IDH-wildtype), Astrocytoma IDH-mutant (Grade 4)
Previous first-line treatment with at least radiotherapy (and temozolomide in the case of glioblastoma or astrocytoma IDH-mutant (grade 4))
Documented recurrence by diagnostic biopsy or contrast-enhanced magnetic resonance imaging (MRI) per RANO 2.0 criteria
At least one measurable lesion per RANO 2.0 meeting the following criteria: Contrast-enhancing or non-enhancing lesions with clearly defined margins by MRI Scan, with both perpendicular diameters on a single slice of at least 10 mm, visible on two or more slices that are preferably, at most, 3 mm apart with 0-mm interslice gap.
Age ≥ 13
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (age ≥ 16) or Lansky of ≥ 60 (age <16)
Disease status confirmed with baseline imaging performed within 28 days of Day 1 of trial treatment. Patients with extracranial metastatic or leptomeningeal disease will be excluded (see Section 5.2)
Subjects must be on a stable or decreasing dose of corticosteroids for at least 7 days before enrollment
Patients must have organ and marrow function as defined below:
Eligibility Guidelines of Organ and Marrow Function Hematologic Absolute neutrophil count (ANC) ≥ 1.5 x 109/L Hemoglobin ≥ 9.0 g/dL Platelets ≥ 75 x 109/L PT/INR and PTT ≤ 1.5 X ULN Hepatic Total bilirubin ≤ 1.5 X ULN (except subjects with known Gilbert syndrome, who can have total bilirubin < 3.0 mg/dL AST and ALT ≤ 3.0 X ULN Renal Creatinine OR Calculated creatinine clearance OR 24-hour urine creatinine clearance ≤ 2 X ULN
50 mL/min
50 ml/min
Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours of starting therapy
WOCBP must agree to follow instructions for methods of contraception
Men who are sexually active with WOCBP must agree to follow instructions for methods of contraception
Investigators will counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and implications of an unexpected pregnancy. At a minimum subjects must agree to the use of two methods of contraception, with one method being highly effective and the other method being either highly effective or less effective: starting at ICF or first dose and continuing 6 months after last dose of trial treatment:
Highly effective methods of contraception Male condoms with spermicide Hormonal methods including combined oral contraceptive pills, vaginal ring, injectables, implants, and intrauterine devices (IUD) Non-hormonal IUD Tubal ligation Vasectomy Complete Abstinence
Less effective methods of contraception Diaphragm with spermicide Cervical cap with spermicide Vaginal sponge Male condom without spermicide Progestin only pills Female condom
An interval of ≥ 2 weeks from major surgery
An interval of ≥ 4 weeks from chemotherapy, radiotherapy, or other investigational agents

You may not qualify if…

Presence of extracranial metastatic or leptomeningeal disease
Patients with diffuse intrinsic pontine glioma, defined as tumors with a pontine epicenter and diffuse involvement of the pons
Patients must not have active autoimmune disease that has required systemic treatment in the past 2 years (e.g. use of disease modifying agents, corticosteroids, or immunosuppressive drugs)
Prior azacitidine for the treatment of cancer (prior administration of nivolumab or other immune checkpoint inhibitor is allowed)
Subjects with major medical, neurologic, or psychiatric condition who are judged to be unable to fully comply with trial therapy or assessments
Positive test for hepatitis B or C virus indicating acute or chronic infection, given the risk of reactivation with checkpoint inhibition
Known history of testing positive for HIV or known acquired immunodeficiency syndrome (AIDS), due to the unknown effects of HIV on the immune response to intrathecal azacitidine and nivolumab
Patients with a history of pneumonitis
Evidence of active infection requiring treatment with IV antibiotics ≤ 7 days prior to initiation of trial therapy.
History of allergy to trial drug components
Prisoners or subjects involuntarily incarcerated
Patients of all genders, races, and ethnicities are invited to participate.

Where it is running

Holden Comprehensive Cancer Center — Iowa City, Iowa, United States

Full record on ClinicalTrials.gov

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