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

NCT05457959 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 22-000581NCI-2022-05326
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Diffuse Hemispheric Glioma, H3 G34-Mutant

Outcome Measures

Primary Outcomes (1)

• 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.

  Start of treatment up to 100 days post-treatment

Secondary Outcomes (2)

• Increased tumor-infiltrating lymphocyte (TIL) density

  Up to 2 years

• Oligoclonal T cell expansion

  Up to 2 years

Study Arms (6)

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.

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.

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.

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.

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.

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.

Biological: Dendritic Cell Tumor Peptide Vaccine; Biological: Nivolumab; Drug: Poly ICLC

Interventions

Dendritic Cell Tumor Peptide Vaccine BIOLOGICAL

Given ID

Also known as: DC tumor peptide vaccine, dendritic cells pulsed with tumor peptide

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)

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, Ipilimumab Biosimilar CS1002, MDX-010, MDX-CTLA4, Yervoy

Cohort I Arm B (placebo, nivolumab, ipilimumab); Cohort I Arm C (ppDC, nivolumab, ipilimumab)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Cohort I Arm A (ppDC, placebo); Cohort I Arm B (placebo, nivolumab, ipilimumab); Cohort I Arm C (ppDC, nivolumab, ipilimumab)

Nivolumab BIOLOGICAL

Given IV

Also known as: BMS-936558, CMAB819, MDX-1106, NIVO, Nivolumab Biosimilar CMAB819, ONO-4538, Opdivo

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 Administration DRUG

Given ID

Cohort I Arm B (placebo, nivolumab, ipilimumab); Cohort II Arm B (placebo, nivolumab)

Poly ICLC DRUG

Given IM

Also known as: 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

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)

Resection PROCEDURE

Undergo standard of care surgical resection

Also known as: Surgical Resection

Cohort I Arm A (ppDC, placebo); Cohort I Arm B (placebo, nivolumab, ipilimumab); Cohort I Arm C (ppDC, nivolumab, ipilimumab)

Eligibility Criteria

• Age: 13 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Interventions

Ipilimumab; CTLA-4 Antigen; Leukapheresis; Nivolumab; poly ICLC

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Anthony C Wang

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2022
• First Posted: July 14, 2022
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: February 24, 2025

Record last verified: 2024-03

Locations

US (1)