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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

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ClinicalTrials.gov Identifier: NCT05457959
Recruitment Status : Not yet recruiting
First Posted : July 14, 2022
Last Update Posted : October 17, 2022
Sponsor:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Brief 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). 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.

Condition or disease Intervention/treatment Phase
Diffuse Hemispheric Glioma, H3 G34-Mutant Biological: Dendritic Cell Tumor Peptide Vaccine Biological: Ipilimumab Procedure: Leukapheresis Biological: Nivolumab Drug: Placebo Administration Drug: Poly ICLC Procedure: Resection Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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
Estimated Study Start Date : January 1, 2023
Estimated Primary Completion Date : May 13, 2029
Estimated Study Completion Date : May 13, 2030

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vaccines

Arm Intervention/treatment
Placebo Comparator: Cohort I Arm A (ppDC, placebo)
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.
Biological: Dendritic Cell Tumor Peptide Vaccine
Given ID
Other Names:
  • DC tumor peptide vaccine
  • dendritic cells pulsed with tumor peptide

Procedure: Leukapheresis
Undergo leukapheresis
Other Names:
  • Leukocytopheresis
  • Therapeutic Leukopheresis

Drug: Placebo Administration
Given IV

Drug: Poly ICLC
Given IM
Other Names:
  • Hiltonol
  • Poly I:Poly C with Poly-L-Lysine Stabilizer
  • poly-ICLC
  • PolyI:PolyC with Poly-L-Lysine Stabilizer
  • Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
  • Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose
  • Stabilized Polyriboinosinic/Polyribocytidylic Acid

Procedure: Resection
Undergo standard of care surgical resection
Other Name: Surgical Resection

Placebo Comparator: Cohort I Arm B (placebo, nivolumab, ipilimumab)
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.
Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Procedure: Leukapheresis
Undergo leukapheresis
Other Names:
  • Leukocytopheresis
  • Therapeutic Leukopheresis

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • CMAB819
  • MDX-1106
  • NIVO
  • Nivolumab Biosimilar CMAB819
  • ONO-4538
  • Opdivo

Drug: Placebo Administration
Given ID

Drug: Poly ICLC
Given IM
Other Names:
  • Hiltonol
  • Poly I:Poly C with Poly-L-Lysine Stabilizer
  • poly-ICLC
  • PolyI:PolyC with Poly-L-Lysine Stabilizer
  • Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
  • Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose
  • Stabilized Polyriboinosinic/Polyribocytidylic Acid

Procedure: Resection
Undergo standard of care surgical resection
Other Name: Surgical Resection

Experimental: Cohort I Arm C (ppDC, nivolumab, ipilimumab)
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.
Biological: Dendritic Cell Tumor Peptide Vaccine
Given ID
Other Names:
  • DC tumor peptide vaccine
  • dendritic cells pulsed with tumor peptide

Biological: Ipilimumab
Given IV
Other Names:
  • Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody
  • BMS-734016
  • Ipilimumab Biosimilar CS1002
  • MDX-010
  • MDX-CTLA4
  • Yervoy

Procedure: Leukapheresis
Undergo leukapheresis
Other Names:
  • Leukocytopheresis
  • Therapeutic Leukopheresis

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • CMAB819
  • MDX-1106
  • NIVO
  • Nivolumab Biosimilar CMAB819
  • ONO-4538
  • Opdivo

Drug: Poly ICLC
Given IM
Other Names:
  • Hiltonol
  • Poly I:Poly C with Poly-L-Lysine Stabilizer
  • poly-ICLC
  • PolyI:PolyC with Poly-L-Lysine Stabilizer
  • Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
  • Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose
  • Stabilized Polyriboinosinic/Polyribocytidylic Acid

Procedure: Resection
Undergo standard of care surgical resection
Other Name: Surgical Resection

Experimental: Cohort II Arm A (ppDC, placebo)
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.
Biological: Dendritic Cell Tumor Peptide Vaccine
Given ID
Other Names:
  • DC tumor peptide vaccine
  • dendritic cells pulsed with tumor peptide

Drug: Placebo Administration
Given IV

Drug: Poly ICLC
Given IM
Other Names:
  • Hiltonol
  • Poly I:Poly C with Poly-L-Lysine Stabilizer
  • poly-ICLC
  • PolyI:PolyC with Poly-L-Lysine Stabilizer
  • Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
  • Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose
  • Stabilized Polyriboinosinic/Polyribocytidylic Acid

Placebo Comparator: Cohort II Arm B (placebo, nivolumab)
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.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • CMAB819
  • MDX-1106
  • NIVO
  • Nivolumab Biosimilar CMAB819
  • ONO-4538
  • Opdivo

Drug: Placebo Administration
Given ID

Drug: Poly ICLC
Given IM
Other Names:
  • Hiltonol
  • Poly I:Poly C with Poly-L-Lysine Stabilizer
  • poly-ICLC
  • PolyI:PolyC with Poly-L-Lysine Stabilizer
  • Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
  • Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose
  • Stabilized Polyriboinosinic/Polyribocytidylic Acid

Experimental: Cohort II Arm C (ppDC, nivolumab)
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.
Biological: Dendritic Cell Tumor Peptide Vaccine
Given ID
Other Names:
  • DC tumor peptide vaccine
  • dendritic cells pulsed with tumor peptide

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • CMAB819
  • MDX-1106
  • NIVO
  • Nivolumab Biosimilar CMAB819
  • ONO-4538
  • Opdivo

Drug: Poly ICLC
Given IM
Other Names:
  • Hiltonol
  • Poly I:Poly C with Poly-L-Lysine Stabilizer
  • poly-ICLC
  • PolyI:PolyC with Poly-L-Lysine Stabilizer
  • Polyinosinic-Polycytidylic Acid Stabilized with Polylysine and Carboxymethylcellulose
  • Polyriboinosinic-Polyribocytidylic Acid-Polylysine Carboxymethylcellulose
  • Stabilized Polyriboinosinic/Polyribocytidylic Acid




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Increased tumor-infiltrating lymphocyte (TIL) density [ Time Frame: Up to 2 years ]
    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.

  2. Oligoclonal T cell expansion [ Time Frame: Up to 2 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   13 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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)

Exclusion Criteria:

  • 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
    • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05457959


Locations
Layout table for location information
United States, California
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States, 90095
Contact: Anthony C. Wang       acwang@mednet.ucla.edu   
Principal Investigator: Anthony C. Wang         
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
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Principal Investigator: Anthony C Wang UCLA / Jonsson Comprehensive Cancer Center
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Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT05457959    
Other Study ID Numbers: 22-000581
NCI-2022-05326 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Posted: July 14, 2022    Key Record Dates
Last Update Posted: October 17, 2022
Last Verified: October 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Poly I-C
Nivolumab
Ipilimumab
Carboxymethylcellulose Sodium
Vaccines
Poly ICLC
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Interferon Inducers
Laxatives
Gastrointestinal Agents
Antiviral Agents
Anti-Infective Agents