Diffuse Hemispheric Glioma, H3 G34-MutantPhase 1NCT05457959
Peptide-Pulsed Dendritic Cell Vaccination in Combination With Nivolumab and Ipilimumab for the Treatment of Recurrent and/or Progressive Diffuse Hemispheric Glioma, H3 G34-mutant
A Phase 1 study testing Dendritic Cell Tumor Peptide Vaccine, Ipilimumab and Leukapheresis in people with Diffuse Hemispheric Glioma, H3 G34-Mutant, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
This phase I trial tests peptide-pulsed dendritic cell vaccination in combination with immunotherapy nivolumab and ipilimumab for the treatment diffuse hemispheric glioma with a H3 G34 mutation that has come back (recurrent) and/or is growing, spreading, or getting worse (progressive). Read more about this study
- Who is it for?
- Ages 13 to 60 years
- Conditions the study is for
- Diffuse Hemispheric Glioma, H3 G34-Mutant
- What is being tested?
- Dendritic Cell Tumor Peptide Vaccine, Ipilimumab and Leukapheresis
- Type of treatment
- Vaccines, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2024to 1 Dec 2030
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Participants between the ages of 13 and 60 years with pathologically-confirmed diagnosis of (or pathology re-review consistent with) DHG will be enrolled in this study
- All participants must be undergoing clinically indicated resection surgical resection with the goal of cytoreduction
- Participants must undergo human leukocyte antigen (HLA) testing
- A female participant who has childbearing potential must have negative urine or serum pregnancy test 72 hours prior to the first dose and be willing to use adequate method of contraception for course of study and 120 days after last dose
- The participant (or legally acceptable representative if applicable) provides informed consent (and written assent from minors) for the trial
- Have unequivocal evidence for contrast-enhancing tumor progression by modified response assessment in neuro-oncology (mRANO) criteria based on MRI scan within 72 days prior to enrollment. This criterion will be reviewed by investigators prior to enrollment
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- An interval of the following durations prior to enrollment:
- At least 14 days from prior surgical resection
- At least 7 days from prior stereotactic biopsy
- At least 12 weeks from prior radiotherapy, unless there is unequivocal histologic confirmation of tumor progression
- At least 23 days from prior chemotherapy
- At least 42 days from nitrosureas
- Have sufficient archival tumor tissue confirming high-grade glioma (HGG) or variants for submission following registration. The following amount of tissue is required: 1 formalin-fixed, paraffin embedded (FFPE) tissue block (preferred) or 10 FFPE unstained slides (5 um thick)
- Have a Karnofsky Performance Status (KPS) >= 70, if participant age >= 16. Have a Lansky Performance Status (LPS) >= 70, if participant age < 16
- Absolute neutrophil count (ANC) >= 1500/uL (within 14 days prior to start of study treatment)
- Platelets >= 100 000/uL (microliter) (within 14 days prior to the start of study treatment)
- Hemoglobin >= 9.0 g/dL or >= 5.6 mmol/L (within 14 days prior to the start of study treatment)
- Note: Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks
- Creatinine =< 1.5 x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) >= 30 mL/min for participant with creatinine levels > 1.5 x institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl) (within 14 days prior to the start of study treatment)
- Note: Creatinine clearance (CrCl) should be calculated per institutional standard
- Total bilirubin =< 1.5 x ULN OR direct bilirubin =< ULN for participants with total bilirubin levels > 1.5 x ULN (within 14 days prior to the start of study treatment)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x ULN (=< 5 x ULN for participants with liver metastases) (within 14 days prior to the start of study treatment)
- International normalized ratio (INR) OR prothrombin time (PT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or activated partial thromboplastin time (aPTT) is within therapeutic range of intended use of anticoagulants (within 14 days prior to the start of study treatment)
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants (within 14 days prior to the start of study treatment)
Who cannot join
- Age < 13 years or > 60 years
- Have had more than 2 separately-treated recurrences of the index tumor
- A woman of child-bearing potential who has a positive urine pregnancy test within 72 hours prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory target (e.g., CTLA-4, OX 40, CD137)
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to enrollment
- Note: Participants must have recovered from all adverse events (AEs) due to previous therapies to =< grade 1 or baseline. Participants with =< grade 2 neuropathy may be eligible
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- Note: If participant received major surgical resection, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment
- Has received prior radiotherapy within 12 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=< 12 weeks of radiotherapy) to non-central nervous system (CNS) disease
- Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment
- Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent
- Has a diagnosis of immunodeficiency or is receiving chronic systemic corticosteroid therapy (dosing exceeding 1 mg/kg/day of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
- Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded
- Has severe hypersensitivity (>= grade 3) to nivolumab or ipilimumab, and/or any of its excipients
- Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has an active infection requiring systemic therapy
- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV) (defined as HCV ribonucleic acid (RNA) is detected) infection
- Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority
- Has a known history of active tuberculosis (bacillus tuberculosis)
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
- Kidney dysfunction precluding administration of gadolinium-based contrast
- Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
About this study
Official title: A Placebo-Controlled, Single (Participant) Blind Trial to Evaluate the Safety, Tolerability, and Early Immunogenicity of Peptide-Pulsed Dendritic Cell Vaccination With Nivolumab and Ipilimumab in Recurrent and/or Progressive Diffuse Hemispheric Glioma, H3 G34-Mutant
This phase I trial tests peptide-pulsed dendritic cell vaccination in combination with immunotherapy nivolumab and ipilimumab for the treatment diffuse hemispheric glioma with a H3 G34 mutation that has come back (recurrent) and/or is growing, spreading, or getting worse (progressive). Vaccines made from the patient's own white blood cells and peptide-pulsed dendritic cells may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, also may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Together, the vaccine and immunotherapy drugs given before and after surgical resection (the removal of tumor cells through surgery) may improve stimulation of anti-tumor immunity to help fight the cancer.
Read the detailed description
PRIMARY OBJECTIVE:
- To evaluate the safety and tolerability of nivolumab/ipilimumab and peptide-pulsed dendritic cell (ppDC) vaccination in diffuse hemispheric glioma H3 G34-mutant (DHG) participants undergoing surgical resection.
SECONDARY OBJECTIVES:
- To determine whether nivolumab/ipilimumab and/or ppDC vaccination facilitate intratumoral T cell-mediated anti-tumor immune activation in progressive DHG.
II. To determine whether nivolumab/ipilimumab and/or ppDC vaccination stimulate systemic adaptive anti-tumor immunity in progressive DHG.
OUTLINE: Patients are sequentially assigned to 2 cohorts.
COHORT 1 (Pre-Surgical Resection): Patients are randomized to 1 of 3 arms.
ARM A: Patients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC intradermally (ID) in both arms with poly ICLC intramuscularly (IM) on day -10 and placebo intravenously (IV) on day -9 prior to standard of care surgical resection.
ARM B: Patients undergo leukapheresis 10 days prior to first injection. Patients receive placebo ID in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection.
ARM C: Patients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC ID divided in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection.
COHORT 2 (Post-Surgical Resection): Patients are assigned to 1 of 3 arms.
ARM A: Within 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and placebo IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity.
ARM B: Within 30 days of surgical resection, patients receive placebo ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity.
ARM C: Within 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and 6 months and every 6 months for up to 2 years.
- Being tested
- Dendritic Cell Tumor Peptide Vaccine, Ipilimumab, Leukapheresis, Nivolumab, Placebo Administration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dendritic Cell Tumor Peptide VaccineBiological
Also called DC tumor peptide vaccine, dendritic cells pulsed with tumor peptide
Given ID
IpilimumabBiological
Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010
Given IV
LeukapheresisProcedure or surgery
Also called Leukocytopheresis, Therapeutic Leukopheresis
Undergo leukapheresis
NivolumabBiological
Also called BMS-936558, CMAB819, MDX-1106, NIVO
Given IV
Placebo AdministrationDrug
Given ID
Placebo AdministrationDrug
Given IV
Poly ICLCDrug
Also called Hiltonol, Poly I:Poly C with Poly-L-Lysine Stabilizer, poly-ICLC, PolyI:PolyC with Poly-L-Lysine Stabilizer
Given IM
ResectionProcedure or surgery
Also called Surgical Resection
Undergo standard of care surgical resection
| Study group | Role | What they receive |
|---|---|---|
| Cohort I Arm A (ppDC, placebo) | Placebo comparator | Patients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC ID in both arms with poly ICLC IM on day -10 and placebo IV on day -9 prior to standard of care surgical resection. Receives: Biological: Dendritic Cell Tumor Peptide Vaccine; Procedure: Leukapheresis; Drug: Placebo Administration; Drug: Poly ICLC; Procedure: Resection |
| Cohort I Arm B (placebo, nivolumab, ipilimumab) | Placebo comparator | Patients undergo leukapheresis 10 days prior to first injection. Patients receive placebo ID in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection. Receives: Biological: Ipilimumab; Procedure: Leukapheresis; Biological: Nivolumab; Drug: Placebo Administration; Drug: Poly ICLC; Procedure: Resection |
| Cohort I Arm C (ppDC, nivolumab, ipilimumab) | Experimental | Patients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC ID divided in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection. Receives: Biological: Dendritic Cell Tumor Peptide Vaccine; Biological: Ipilimumab; Procedure: Leukapheresis; Biological: Nivolumab; Drug: Poly ICLC; Procedure: Resection |
| Cohort II Arm A (ppDC, placebo) | Experimental | Within 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and placebo IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity. Receives: Biological: Dendritic Cell Tumor Peptide Vaccine; Drug: Placebo Administration; Drug: Poly ICLC |
| Cohort II Arm B (placebo, nivolumab) | Placebo comparator | Within 30 days of surgical resection, patients receive placebo ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity. Receives: Biological: Nivolumab; Drug: Placebo Administration; Drug: Poly ICLC |
| Cohort II Arm C (ppDC, nivolumab) | Experimental | Within 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity. Receives: Biological: Dendritic Cell Tumor Peptide Vaccine; Biological: Nivolumab; Drug: Poly ICLC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
Safety and tolerability will be monitored by the University of California, Los Angeles (UCLA) Data Safety Monitoring Board (DSMB) incorporating regular reviews with the investigators in this pilot surgical trial. Adverse events will be monitored throughout the trial and graded in severity according to the guidelines outlined in the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
Measured: Start of treatment up to 100 days post-treatment
Secondary outcomes (2)
Increased tumor-infiltrating lymphocyte (TIL) density
Tumor tissue will be analyzed for increased TIL density, quantified as number of cytotoxic T lymphocytes (CTLs) per nucleated cell, or increased T cell activation/ decreased T cell exhaustion marker expression. Mean differences for all outcomes of interest will be estimated for (group A versus group B, group A versus C, and group B versus C). Sampling uncertainty in estimation will be reported using 95% Confidence Intervals. A two-sample t-test with Bonferroni adjustment will be performed to test each of these two hypotheses.
Measured: Up to 2 years
Oligoclonal T cell expansion
Peripheral blood will be analyzed for oligoclonal T cell expansion by T cell receptor (TCR)VBeta sequencing. Mean differences for all outcomes of interest will be estimated for (group A versus group B, group A versus C, and group B versus C). Sampling uncertainty in estimation will be reported using 95% Confidence Intervals. A two-sample t-test with Bonferroni adjustment will be performed to test each of these two hypotheses.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2022
- Study start1 Dec 2024 (estimated)
- Primary completion1 Dec 2029 (estimated)
- Study completion1 Dec 2030 (estimated)
Why it stopped: Never opened
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diffuse Hemispheric Glioma, H3 G34-MutantStudies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anthony C Wang, Principal investigator, UCLA / Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05457959
- Sponsor's protocol ID
- 22-000581
- Other IDs
- NCI-2022-05326
- Status last verified
- Mar 2024
- First submitted
- 7 Jul 2022
- Last updated
- 24 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Placebo-Controlled, Single (Participant) Blind Trial to Evaluate the Safety, Tolerability, and Early Immunogenicity of Peptide-Pulsed Dendritic Cell Vaccination With Nivolumab and Ipilimumab in Recurrent and/or Progressive Diffuse Hemispheric Glioma, H3 G34-Mutant
- ClinicalTrials.gov ID
- NCT05457959
- Acronym / sponsor ID
- 22-000581
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Never opened
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 1 Dec 2024 (estimated)
- Primary completion
- 1 Dec 2029 (estimated)
- Study completion
- 1 Dec 2030 (estimated)
- First posted
- 14 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase I trial tests peptide-pulsed dendritic cell vaccination in combination with immunotherapy nivolumab and ipilimumab for the treatment diffuse hemispheric glioma with a H3 G34 mutation that has come back (recurrent) and/or is growing, spreading, or getting worse (progressive). Vaccines made from the patient's own white blood cells and peptide-pulsed dendritic cells may help the body build an effective immune response to kill tumor cells. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, also may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Together, the vaccine and immunotherapy drugs given before and after surgical resection (the removal of tumor cells through surgery) may improve stimulation of anti-tumor immunity to help fight the cancer.
Detailed description
PRIMARY OBJECTIVE:
- To evaluate the safety and tolerability of nivolumab/ipilimumab and peptide-pulsed dendritic cell (ppDC) vaccination in diffuse hemispheric glioma H3 G34-mutant (DHG) participants undergoing surgical resection.
SECONDARY OBJECTIVES:
- To determine whether nivolumab/ipilimumab and/or ppDC vaccination facilitate intratumoral T cell-mediated anti-tumor immune activation in progressive DHG.
II. To determine whether nivolumab/ipilimumab and/or ppDC vaccination stimulate systemic adaptive anti-tumor immunity in progressive DHG.
OUTLINE: Patients are sequentially assigned to 2 cohorts.
COHORT 1 (Pre-Surgical Resection): Patients are randomized to 1 of 3 arms.
ARM A: Patients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC intradermally (ID) in both arms with poly ICLC intramuscularly (IM) on day -10 and placebo intravenously (IV) on day -9 prior to standard of care surgical resection.
ARM B: Patients undergo leukapheresis 10 days prior to first injection. Patients receive placebo ID in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection.
ARM C: Patients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC ID divided in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection.
COHORT 2 (Post-Surgical Resection): Patients are assigned to 1 of 3 arms.
ARM A: Within 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and placebo IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity.
ARM B: Within 30 days of surgical resection, patients receive placebo ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity.
ARM C: Within 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 30 days and 6 months and every 6 months for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Single blind (participant)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Cohort I Arm A (ppDC, placebo) | Placebo comparator | Biological: Dendritic Cell Tumor Peptide Vaccine, Procedure: Leukapheresis, Drug: Placebo Administration, Drug: Poly ICLC, Procedure: ResectionPatients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC ID in both arms with poly ICLC IM on day -10 and placebo IV on day -9 prior to standard of care surgical resection. |
| Cohort I Arm B (placebo, nivolumab, ipilimumab) | Placebo comparator | Biological: Ipilimumab, Procedure: Leukapheresis, Biological: Nivolumab, Drug: Placebo Administration, Drug: Poly ICLC, Procedure: ResectionPatients undergo leukapheresis 10 days prior to first injection. Patients receive placebo ID in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection. |
| Cohort I Arm C (ppDC, nivolumab, ipilimumab) | Experimental | Biological: Dendritic Cell Tumor Peptide Vaccine, Biological: Ipilimumab, Procedure: Leukapheresis, Biological: Nivolumab, Drug: Poly ICLC, Procedure: ResectionPatients undergo leukapheresis 10 days prior to first injection. Patients receive ppDC ID divided in both arms with poly ICLC IM on day -10 and nivolumab IV and ipilimumab IV on day -9 prior to standard of care surgical resection. |
| Cohort II Arm A (ppDC, placebo) | Experimental | Biological: Dendritic Cell Tumor Peptide Vaccine, Drug: Placebo Administration, Drug: Poly ICLCWithin 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and placebo IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity. |
| Cohort II Arm B (placebo, nivolumab) | Placebo comparator | Biological: Nivolumab, Drug: Placebo Administration, Drug: Poly ICLCWithin 30 days of surgical resection, patients receive placebo ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity. |
| Cohort II Arm C (ppDC, nivolumab) | Experimental | Biological: Dendritic Cell Tumor Peptide Vaccine, Biological: Nivolumab, Drug: Poly ICLCWithin 30 days of surgical resection, patients receive ppDC ID in both arms with poly ICLC IM and nivolumab IV on day 1 of each cycle. Treatment repeats every 2 weeks for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Post-treatment, patients may receive nivolumab IV on day 1 of each cycle. Cycles repeat every 4 weeks for up to 24 months following surgical resection in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 13 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (24 listed)
- Participants between the ages of 13 and 60 years with pathologically-confirmed diagnosis of (or pathology re-review consistent with) DHG will be enrolled in this study
- All participants must be undergoing clinically indicated resection surgical resection with the goal of cytoreduction
- Participants must undergo human leukocyte antigen (HLA) testing
- A female participant who has childbearing potential must have negative urine or serum pregnancy test 72 hours prior to the first dose and be willing to use adequate method of contraception for course of study and 120 days after last dose
- The participant (or legally acceptable representative if applicable) provides informed consent (and written assent from minors) for the trial
Key exclusion criteria (25 listed)
- Age < 13 years or > 60 years
- Have had more than 2 separately-treated recurrences of the index tumor
- A woman of child-bearing potential who has a positive urine pregnancy test within 72 hours prior to enrollment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory target (e.g., CTLA-4, OX 40, CD137)
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dendritic Cell Tumor Peptide VaccineAlso: DC tumor peptide vaccine, dendritic cells pulsed with tumor peptideGiven ID | Biological | Cohort I Arm A (ppDC, placebo), Cohort I Arm C (ppDC, nivolumab, ipilimumab), Cohort II Arm A (ppDC, placebo), Cohort II Arm C (ppDC, nivolumab) |
| IpilimumabAlso: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010Given IV | Biological | Cohort I Arm B (placebo, nivolumab, ipilimumab), Cohort I Arm C (ppDC, nivolumab, ipilimumab) |
| LeukapheresisAlso: Leukocytopheresis, Therapeutic LeukopheresisUndergo leukapheresis | Procedure or surgery | Cohort I Arm A (ppDC, placebo), Cohort I Arm B (placebo, nivolumab, ipilimumab), Cohort I Arm C (ppDC, nivolumab, ipilimumab) |
| NivolumabAlso: BMS-936558, CMAB819, MDX-1106, NIVOGiven IV | Biological | Cohort I Arm B (placebo, nivolumab, ipilimumab), Cohort I Arm C (ppDC, nivolumab, ipilimumab), Cohort II Arm B (placebo, nivolumab), Cohort II Arm C (ppDC, nivolumab) |
| Placebo AdministrationGiven ID | Drug | Cohort I Arm B (placebo, nivolumab, ipilimumab), Cohort II Arm B (placebo, nivolumab) |
| Placebo AdministrationGiven IV | Drug | Cohort I Arm A (ppDC, placebo), Cohort II Arm A (ppDC, placebo) |
| Poly ICLCAlso: Hiltonol, Poly I:Poly C with Poly-L-Lysine Stabilizer, poly-ICLC, PolyI:PolyC with Poly-L-Lysine StabilizerGiven IM | Drug | Cohort I Arm A (ppDC, placebo), Cohort I Arm B (placebo, nivolumab, ipilimumab), Cohort I Arm C (ppDC, nivolumab, ipilimumab), Cohort II Arm A (ppDC, placebo), Cohort II Arm B (placebo, nivolumab), Cohort II Arm C (ppDC, nivolumab) |
| ResectionAlso: Surgical ResectionUndergo standard of care surgical resection | Procedure or surgery | Cohort I Arm A (ppDC, placebo), Cohort I Arm B (placebo, nivolumab, ipilimumab), Cohort I Arm C (ppDC, nivolumab, ipilimumab) |
Primary outcome
Incidence of adverse events
Time frame: Start of treatment up to 100 days post-treatment
Safety and tolerability will be monitored by the University of California, Los Angeles (UCLA) Data Safety Monitoring Board (DSMB) incorporating regular reviews with the investigators in this pilot surgical trial. Adverse events will be monitored throughout the trial and graded in severity according to the guidelines outlined in the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
2 secondary outcomes
Increased tumor-infiltrating lymphocyte (TIL) density
Time frame: Up to 2 years
Oligoclonal T cell expansion
Time frame: Up to 2 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony C Wang principal investigator
UCLA / Jonsson Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Dendritic Cell Tumor Peptide Vaccine, Ipilimumab and Leukapheresis in people with Diffuse Hemispheric Glioma, H3 G34-Mutant, run by Jonsson Comprehensive Cancer Center 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 24 inclusion and 25 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: withdrawn, as of the sponsor's last update on 24 Feb 2025. 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. Some participants in this study may receive a placebo. 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?
The study was withdrawn before enrolling participants, so there are no results.
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: Start of treatment up to 100 days post-treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Feb 2025.