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Glioblastoma (GBM)Phase 1NCT06896110

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

A Phase 1 study testing Nivolumab, Azacitidine (AZA) and lumbar puncture in people with Glioblastoma (GBM) and Diffuse Midline Glioma (DMG), run by Andrew P. Groves at 1 site in United States.

Enrolling by invitation

Enrolling by invitation. The study team selects and invites participants, usually from an existing group of patients.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 13 years and older
What is being tested?
Nivolumab, Azacitidine (AZA) and lumbar puncture
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
1 siteUnited States
Study dates
5 Jun 2025to Mar 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site

  • Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

Other trials in United States

About this study

Official title: Phase 1 Trial of Intrathecal Azacitidine and Nivolumab in Patients With Recurrent High-grade Glioma

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.

Read the detailed description

PRIMARY OUTCOME Phase I To determine the safety and maximum tolerated dose (MTD) of intrathecal (IT) azacitidine in combination with IT nivolumab in patients with recurrent high-grade glioma

Expansion Cohort To estimate the overall response rate (ORR)

SECONDARY OUTCOMES

To estimate:

  1. Duration of response (DOR)
  2. Progression-free survival (PFS)
  3. Overall survival (OS)

EXPLORATORY OUTCOMES Changes in immune profiling (flow cytometry, cytokine/chemokine analysis) and circulating tumor DNA (ctDNA) biomarkers (quantification, DNA methylation)

Being tested
Nivolumab, Azacitidine (AZA), lumbar puncture, MRI Contrast
Medical subject headings
Glioblastoma, Astrocytoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabDrug

    Intrathecal nivolumab will be given at a flat dose of 40 mg

  • Azacitidine (AZA)Drug

    Intrathecal azacitidine will be dose-escalated with 4 dose levels (5, 10, 20, 40 mg) using a 3+3 design.

  • lumbar punctureProcedure or surgery

    Lumbar puncture for intrathecal delivery and collection of CSF

  • MRI ContrastDiagnostic test

    MRI Brain and full Spine (with and without contrast) will be performed prior to enrollment. During trial therapy, MRI Brain (with and without contrast) will be performed after cycle 1 and after that every 8 weeks (e.g. after cycle 3, cycle 5, etc…)

Study groups in NCT06896110
Study groupRoleWhat they receive
Treatment (IT nivolumab + IT azacitidine)ExperimentalPatients will receive intrathecal azacitidine on day 1, 8, and 22 of cycle 1 (34 day cycle). Intrathecal nivolumab will be given at a flat dose of 40 mg on day 8 and 22. Each subsequent cycle will be 28 days with intrathecal azacitidine and intrathecal nivolumab given on days 1 and 15. Intrathecal azacitidine will be dose-escalated with 4 dose levels (5, 10, 20, 40 mg) using a 3+3 design. Patients may continue on study in the absence of disease progression or unacceptable toxicity. Patients will have CSF and blood specimen collection on days 1 and 8 of cycle 1, and then day 1 of every-other cycle starting with cycle 2. Patients will undergo MRI at baseline, then every 8 weeks (e.g. after cycle 3, cycle 5, etc…).
Receives: Drug: Nivolumab; Drug: Azacitidine (AZA); Procedure: lumbar puncture; Diagnostic Test: MRI Contrast

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    Adverse events will be graded by the Common Terminology Criteria for Adverse Events version 5.0.

    Measured: 24 months

  2. Maximum tolerated dose (MTD) of intrathecal azacitidine in combination with intrathecal nivolumab

    The MTD will be established using a 3+3 design.

    Measured: 24 months

  3. Overall Response Rate (Expansion Cohort)

    The primary objective of the expansion cohort is to obtain a preliminary estimate of the overall response rate (ORR). ORR will be defined as the proportion of patients with a complete response (CR) or partial response (PR) according to Response Assessment in Neuro-Oncology (RANO) 2.0 criteria

    Measured: 24 months

Secondary outcomes (4)

  1. To estiamte the duration of response (DOR)

    DOR will be defined as the time from first documented complete response (CR) or partial response (PR) to progressive disease (PD) according to RANO 2.0 criteria

    Measured: 24 months

  2. To estimate progression-free survival

    PFS will be defined as the time from trial treatment initiation to first documented progression or death due to any cause.

    Measured: 24 months

  3. To estimate overall survival

    OS will be defined as the time from trial treatment initiation to death due to any cause.

    Measured: 24 months

  4. To assess biomarkers for immunologic and epigenetic effects of therapy

    Changes in CSF and blood immunological profiling by flow cytometry, cytokine/chemokine analysis. Changes in circulating tumor DNA (ctDNA) analysis in CSF

    Measured: 24 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Mar 2025
  2. Study start5 Jun 2025
  3. Primary completionMar 2028 (estimated)
  4. Study completionMar 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06896110
Sponsor's protocol ID
202406429
Status last verified
Oct 2026
First submitted
19 Mar 2025
Last updated
27 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Study protocol and Informed Consent Form (ICF)

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nivolumab, Azacitidine (AZA) and lumbar puncture in people with Glioblastoma (GBM) and Diffuse Midline Glioma (DMG), run by Andrew P. Groves at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: enrolling by invitation, as of the sponsor's last update on 27 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: 24 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06896110.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Oct 2026.

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