Giant Cell GlioblastomaPhase 2NCT03014804
Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen Vaccine and Nivolumab in Treating Patients With Recurrent Glioblastoma
A Phase 2 study testing autologous dendritic cells pulsed with tumor lysate antigen Vaccine, Laboratory Biomarker Analysis and Nivolumab in people with Giant Cell Glioblastoma and Gliosarcoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies the side effects of autologous dendritic cells pulsed with tumor lysate antigen vaccine and nivolumab and to see how well they work in treating patients with glioblastoma that has come back. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Giant Cell Glioblastoma, Gliosarcoma, Oligodendroglioma
- What is being tested?
- autologous dendritic cells pulsed with tumor lysate antigen Vaccine, Laboratory Biomarker Analysis and Nivolumab
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2019to 1 Dec 2022
- Phase
- Phase 2
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PRE-SURGERY SCREENING PROCESS
- Original diagnosis of glioblastoma multiforme (GBM) confirmed by central review
- Radiographic evidence of first recurrence per Response Assessment in Neuro-Oncology (RANO) criteria confirmed by central review
- Surgically accessible, unilateral, recurrent GBM tumor for which extirpative resection, with intent to perform a gross total or near gross total resection, is indicated; a subject may be screened if he or she has had a previous biopsy and is scheduled for a subsequent gross or near gross total resection prior to commencement of other therapies
- Ability to understand and sign the tumor procurement informed consent form indicating awareness of the investigational nature of this study; the consent for tumor tissue donation may be signed by a legally authorized representative (LAR) if allowed by the institution
- Life expectancy of >= 12 weeks
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- Absolute lymphocyte count >= 0.6 x 10^3/mm^3 (0.6 x 10^9/L)
- MGMT promoter methylation status of original tumor is obtainable
- POST-SURGERY, PRIOR TO PRE-LEUKAPHERESIS
- Therapy for recurrent disease must have consisted of surgical resection extending beyond biopsy only, with the intent to achieve gross or near-total resection of the contrast-enhancing tumor mass; subjects who underwent resection confirmed beyond biopsy remain eligible for the screening process; subjects undergoing a biopsy only will be excluded; central confirmation is required before the subject can proceed to leukapheresis
- Patients with recurrent unilateral GBM, confirmed through central pathology (grade IV), without metastases, remain eligible for this protocol
- For the purposes of this study, pathology reports for all histologically confirmed GBM includes the recognized variants of glioblastoma (small cell glioblastoma, giant cell glioblastoma, gliosarcoma, and glioblastoma with oligodendroglial components)
- All subjects must have sufficient tumor lysate protein generated from the resected tumor tissue; this determination will be made by the sponsor's contracted manufacturer and communicated to the clinical site through the sponsor or its designee; this confirmation is not required prior to the pre-leukapheresis visit, but is required before the subject can proceed to leukapheresis
- PRE-LEUKAPHERESIS EVALUATION
- Hemoglobin > 10 g/dL (100 g/L)
- White blood cell count 3.6-11.0 x 10^3/mm^3 (3.6-11.0 x 10^9/L)
- Absolute granulocyte count >= 1.5 x 10^3/mm^3 (1.5 x 10^9/L)
- Absolute lymphocyte count >= 1.0 x 10^3/mm^3 (1.0 x 10^9/L)
- Platelet count >= 100 x 10^3/mm^3 (100 x 10^9/L)
- Eligibility is maintained if these laboratory results are outside of the central laboratory's normal reference ranges or the sample ranges provided above but are not deemed clinically significant by the treating investigator
- Eligibility level of hemoglobin can be reached by transfusion; these values are determined by a central laboratory
- Serum glutamate pyruvate transaminase (SGPT) =< 4.0 times upper limits of normal (ULN)
- Serum glutamic-oxaloacetic transaminase (SGOT) =< 4.0 times ULN
- Alkaline phosphatase =< 4.0 times upper limits of normal (ULN)
- Total bilirubin =< 1.5 mg/dL (25.7 umol/L)
- Blood urea nitrogen (BUN) =< 1.5 times ULN
- Creatinine =< 1.5 times ULN
- Subjects must have a Karnofsky performance status (KPS) rating >= 70 at the pre-leukapheresis visit
- PRIOR TO DAY 0
- Subjects may have received steroid therapy as part of their primary treatment; steroid treatment should be stopped or, if continued steroid use is clinically indicated, be tapered down to no more than 2 mg dexamethasone per day (or equivalent) at least 7 days prior to the first immunization
- White blood cell count >= 2.0 x 10^3/mm^3 (2.0 x 10^9/L)
- Neutrophils >= 1.5 x 10^3/mm^3 (1.5 x 10^9/L)
- Platelets >= 100 x 10^3/mm^3 (100 x 10^9/L)
- Hemoglobin >= 9.0 g/dL (90 g/L)
- Serum creatinine =< 1.5 x upper limit of normal (ULN)
- SGOT (aspartate aminotransferase [AST]) =< 3 x ULN
- SGPT (alanine aminotransferase [ALT]) =< 3 x ULN
- Total bilirubin =< 1.5 x ULN
- Except subjects with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL
- Subjects must have a KPS rating a >= 60 at the pre-enrollment evaluation
Who cannot join
- PRE-SCREENING
- Progression on imaging based on RANO criteria within 12 weeks of conclusion of radiotherapy
- History of other prior malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or other cancers that were deemed fully resolved 5 or more years prior to surgery
- History of active, known, or suspected autoimmune or immunodeficiency disease
- Known human immunodeficiency virus (HIV)-1 or -2 or human T-cell lymphotropic virus (HTLV)-1 or -2 positivity
- Active uncontrolled infection, such as a sexually transmitted disease (STD), herpes, uncontrolled tuberculosis, malaria, etc
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- Known intolerance to cyclophosphamide or other alkylating agents, or any component of any study drug
- History of active immunotherapy, including dendritic cell therapy, T cell therapy, immunization with tumor antigens in any form, any anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways or checkpoint inhibitor therapy such as ipilimumab
- History of severe infusion-related reaction to any biologics therapy
- Females who are gravid or breast-feeding
- Inability to obtain informed consent because of psychiatric or complicating medical problems
- Any known genetic cancer-susceptibility syndromes
- Any positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicative of acute or chronic infection
- AT OR AROUND SURGERY
- Bilateral or metastatic glioblastoma detected at diagnosis, during surgery, or at post-surgical magnetic resonance imaging (MRI); tumors may cross into, but not beyond, the corpus callosum
- Postoperative MRI evidence of biopsy only, without significant tumor resection, confirmed by central reviewer
- Implantation of Gliadel wafers (polifeprosan 20 with carmustine implant) at surgery
- PRE-LEUKAPHERESIS VISIT
- Positive HIV-1, -2, or HTLV-1, -2 tests
- Recipient of organ allografts
- Allergies to reagents used in this study
- Unable to stop or taper steroid treatment to no more than 2 mg of dexamethasone per day (or equivalent) prior to leukapheresis; steroid use should be stopped or tapered down to the lowest clinically acceptable dose approximately 7 days prior to leukapheresis; the leukapheresis visit must be scheduled to occur a minimum of 21 days before the projected day 0
- It is critical to reduce steroid administration to the lowest possible dose, as steroids interfere with DCVax-L manufacturing by hampering the ability of monocytes to adhere to plastic surfaces during purification; leukapheresis should occur at least 21 days prior to the projected date of DCVax-L administration
- Inability or unwillingness to return for required visits and follow-up exams
- Fewer than 6 doses of DCVax-L available for administration
- Continued requirement for medications that might affect immune function; the following are exceptions: nonprescription strength doses of NSAIDS, acetaminophen (paracetamol), or acetylsalicylic acid (aspirin)
- Acute infection: any active viral, bacterial, or fungal infection that requires specific therapy; antibiotic therapy must be completed at least 7 days prior to the first DCVax-L/nivolumab administration
- Fever >= 101.5 degrees Fahrenheit (F) (38.6 degrees Celsius [C]); if considered possibly transient, retesting is allowed
- Unstable or severe intercurrent medical conditions
- Women of child-bearing potential (WOCBP) who are pregnant or lactating or who are not using adequate contraception and willing to do so to avoid pregnancy for 5 months after the week 20 visit
- Males who are sexually active with WOCBP and not willing to use any contraceptive method with a failure rate of less than 1% per year for 7 months after the week 20 visit
- Any dose of steroids exceeding 10 mg/day of prednisone (or equivalent) within 2 weeks prior to study drug administration
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 Phase II Clinical Trial Evaluating Combination Therapy Using DCVax-L (Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen) and Nivolumab (an Anti-PD-1 Antibody) for Subjects With Recurrent Glioblastoma Multiforme
This phase II trial studies the side effects of autologous dendritic cells pulsed with tumor lysate antigen vaccine and nivolumab and to see how well they work in treating patients with glioblastoma that has come back. Vaccines made from a person's tumor cells may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving dendritic cell-autologous lung tumor vaccine and nivolumab may work better in treating patients with glioblastoma.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety and tolerability of the combination treatment of autologous dendritic cells pulsed with tumor lysate antigen vaccine (DCVax-L) and nivolumab.
II. To compare overall survival (OS) from the date of surgery in a pooled evaluation of group 1 subjects receiving DCVax-L and group 2 subjects receiving DCVax-L and nivolumab to recent historical standards.
III. To compare OS between the two groups.
SECONDARY OBJECTIVES:
- Safety. II. Feasibility. III. Tumor response. IV. Immune response. V. Quality of Life (QoL). VI. Overall survival (OS). VII. Overall survival rate at 9, 12, and 18 months. VIII. Progression-free survival (PFS). IX. Evaluation of the safety of the DCVax-L + nivolumab combination regimen.
TERTIARY OBJECTIVES:
- Estimate correlation of quantitative assessments of tumor-infiltrating lymphocyte (TIL) proliferation (CD8+/Ki-67+ staining).
II. Estimate difference in PD-1 and PD-L1 immunohistochemistry expression between density or clonality with clinical responses to combination therapy in recurrent glioblastoma subjects.
III. Estimate differences between outcome groups in monocytic PD-L1 expression at baseline and over time.
IV. Estimate differences between outcome groups in circulating tumor DNA, circulating tumor cells, and CD4+ T cells at baseline and over time.
- Estimate difference in PD-1 and PD-L1 immunohistochemical (IHC) expression between archived and study samples.
VI. Explore patterns of tumor proteomic profiling. VII. Estimate efficacy of combination therapy by progression-free survival (PFS), rates of contrasted tumor change over time, and overall survival (OS).
VIII. Explore effect of nivolumab on TIL proliferation (CD8+/Ki-67+ staining). IX. Explore whether oligoclonal T cell populations within tumor tissue are similarly expanded in peripheral blood after nivolumab, the magnitude of which correlates with clinical responses.
- Explore if changes in specific MRI parameters correlate with tumor and peripheral blood immune responses.
XI. Explore if a mesenchymal gene expression signature present in the initial archived tumor sample correlates with T lymphocytic response in tumor after nivolumab.
XII. Correlate changes of positron emission tomography (PET) in tumor with the following: TIL density or clonality, clinical outcome, T cell measures in peripheral blood, clinical toxicity.
XIII. Correlate changes in PET in lymph nodes with the following: TIL density or clonality, clinical outcome, T cell measures in peripheral blood, clinical toxicity.
XIV. Correlate changes in PET in organ tissue with TIL density or clonality.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients receive dendritic cell-autologous lung tumor vaccine intradermally (ID) on days 0, 7, 14, and weeks 4, 6, 8, 11, 14, 17 and 20.
GROUP II: Patients receive dendritic cell-autologous lung tumor vaccine as in Group I, and nivolumab intravenously (IV) over 30 minutes on days 0, 14, and weeks 4, 6, 8, 11, 14, 17, and 20.
After completion of study treatment, patients are followed up for up to 12 months.
- Conditions
- Giant Cell Glioblastoma, Gliosarcoma, Oligodendroglioma, Recurrent Glioblastoma, Small Cell Glioblastoma
- Being tested
- autologous dendritic cells pulsed with tumor lysate antigen Vaccine, Laboratory Biomarker Analysis, Nivolumab, Quality-of-Life Assessment, Questionnaire Administration
- Medical subject headings
- Glioblastoma, Gliosarcoma, Oligodendroglioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
autologous dendritic cells pulsed with tumor lysate antigen VaccineBiological
Also called DCVax-Lung
Given ID
Laboratory Biomarker AnalysisOther
Correlative studies
NivolumabBiological
Also called BMS-936558, MDX-1106, NIVO, ONO-4538
Given IV
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| Group I (DCVax-L) | Experimental | Patients receive autologous dendritic cells pulsed with tumor lysate antigen vaccine ID on days 0, 7, 14, and weeks 4, 6, 8, 11, 14, 17 and 20. Receives: Biological: autologous dendritic cells pulsed with tumor lysate antigen Vaccine; Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
| Group II (DCVax-L, nivolumab) | Experimental | Patients receive autologous dendritic cells pulsed with tumor lysate antigen vaccine as in Group I, and nivolumab IV over 30 minutes on days 0, 14, and weeks 4, 6, 8, 11, 14, 17, and 20. Receives: Biological: autologous dendritic cells pulsed with tumor lysate antigen Vaccine; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events assessed by National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03
Will be compared between groups and to those reported for historical standards, including subjects treated with nivolumab in prior trials.
Measured: Up to 12 months
Overall Survival (OS)
The overall survival curves will be displayed using a Kaplan-Meier curve for the pooled and individual treatments. A one-sample log-rank test will also be completed as a sensitivity analysis for the same survival rate assumption as the primary efficacy analysis, and a two-sample log-rank test will be used to compare the survival distribution between the two arms.
Measured: Up to 12 months
Secondary outcomes (11)
Overall Survival rate
The overall survival curves will also be displayed using a Kaplan-Meier curve for the pooled and individual treatments. Estimated proportions of surviving subjects at 9 months will be provided along with the two-sided 95% CIs.
Measured: 9 months
Overall Survival rate
The overall survival curves will also be displayed using a Kaplan-Meier curve for the pooled and individual treatments. Estimated proportions of surviving subjects at 12 months will be provided along with the two-sided 95% CIs.
Measured: 12 months
Overall Survival rate
The overall survival curves will also be displayed using a Kaplan-Meier curve for the pooled and individual treatments. Estimated proportions of surviving subjects at 18 months will be provided along with the two-sided 95% CIs.
Measured: 18 months
Progression Free Survival (PFS)
Kaplan Meier estimates will be provided along with the one-sided 95% lower bound on the survival rate. PFS survival will be compared between groups using a log-rank test.
Measured: From treatment initiation to first progression or death assessed up to 12 months.
Quality of Life (QoL)
Will be summarized descriptively for available subjects, and shifts from day 0 will be summarized for post-baseline assessments using the European Organization for Research and Treatment of Cancer (EORTC) Overall Quality of Life (QoL) questionnaire.
Measured: Up to 12 months
Number of participants with complete response (CR)
Rates of CR will be provided at fixed intervals where tumor size is evaluated. Exact two-sided CIs for the response rate will be provided and the denominator will include subjects with available information or who have previously died or progressed. A Fisher's exact test will be used to compare the test that the number of CR, CR+PR, and CR+PR+SD subjects is homogeneous across the treatment arms.
Measured: Up to 12 months of follow up after initiation of treatment
Number of participants with partial response (PR)
Rates of PR will be provided at fixed intervals where tumor size is evaluated. Exact two-sided CIs for the response rate will be provided and the denominator will include subjects with available information or who have previously died or progressed. A Fisher's exact test will be used to compare the test that the number of CR, CR+PR, and CR+PR+SD subjects is homogeneous across the treatment arms.
Measured: Up to 12 months of follow up after initiation of treatment
Number of participants with stable disease (SD)
Rates of SD will be provided at fixed intervals where tumor size is evaluated. Exact two-sided CIs for the response rate will be provided and the denominator will include subjects with available information or who have previously died or progressed. A Fisher's exact test will be used to compare the test that the number of CR, CR+PR, and CR+PR+SD subjects is homogeneous across the treatment arms.
Measured: Up to 12 months of follow up after initiation of treatment
Number of participants with progressive disease (PD)
Rates of PD will be provided at fixed intervals where tumor size is evaluated. Exact two-sided CIs for the response rate will be provided and the denominator will include subjects with available information or who have previously died or progressed. A Fisher's exact test will be used to compare the test that the number of CR, CR+PR, and CR+PR+SD subjects is homogeneous across the treatment arms.
Measured: Up to 12 months of follow up after initiation of treatment
Objective response rate (ORR) defined as the percentage of participants with CR + PR
Rates of ORR will be provided at fixed intervals where tumor size is evaluated.
Measured: Up to 12 months of follow up after initiation of treatment
Response/Stable Disease Rate (RSDR) defined as the percentage of participants demonstrating CR+PR+SD
Rates of RSDR will be provided at fixed intervals where tumor size is evaluated.
Measured: Up to 12 months of follow up after initiation of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2017 (estimated)
- Study start1 Dec 2019 (estimated)
- Primary completion1 Dec 2020 (estimated)
- Study completion1 Dec 2022 (estimated)
Why it stopped: Final contract negotiations
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Giant Cell GlioblastomaStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Northwest Biotherapeutics, Bristol-Myers Squibb, Brain Tumor Funders Collaborative
- Responsible party
- Sponsor
- Investigators
- Timothy Cloughesy, Principal investigator, UCLA / Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03014804
- Sponsor's protocol ID
- 16-001706
- Other IDs
- NCI-2016-01587, 16-001706
- Status last verified
- Aug 2019
- First submitted
- 30 Nov 2016
- Last updated
- 24 Jul 2020
- 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 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial Evaluating Combination Therapy Using DCVax-L (Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen) and Nivolumab (an Anti-PD-1 Antibody) for Subjects With Recurrent Glioblastoma Multiforme
- ClinicalTrials.gov ID
- NCT03014804
- Acronym / sponsor ID
- 16-001706
- Conditions
- Giant Cell Glioblastoma, Gliosarcoma, Oligodendroglioma, Recurrent Glioblastoma, Small Cell Glioblastoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Final contract negotiations
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Northwest Biotherapeutics, Bristol-Myers Squibb, Brain Tumor Funders Collaborative
- Study start
- 1 Dec 2019 (estimated)
- Primary completion
- 1 Dec 2020 (estimated)
- Study completion
- 1 Dec 2022 (estimated)
- First posted
- 9 Jan 2017 (estimated)
- 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 II trial studies the side effects of autologous dendritic cells pulsed with tumor lysate antigen vaccine and nivolumab and to see how well they work in treating patients with glioblastoma that has come back. Vaccines made from a person's tumor cells may help the body build an effective immune response to kill tumor cells. Monoclonal antibodies, such as nivolumab, may interfere with the ability of tumor cells to grow and spread. Giving dendritic cell-autologous lung tumor vaccine and nivolumab may work better in treating patients with glioblastoma.
Detailed description
PRIMARY OBJECTIVES:
- To evaluate the safety and tolerability of the combination treatment of autologous dendritic cells pulsed with tumor lysate antigen vaccine (DCVax-L) and nivolumab.
II. To compare overall survival (OS) from the date of surgery in a pooled evaluation of group 1 subjects receiving DCVax-L and group 2 subjects receiving DCVax-L and nivolumab to recent historical standards.
III. To compare OS between the two groups.
SECONDARY OBJECTIVES:
- Safety. II. Feasibility. III. Tumor response. IV. Immune response. V. Quality of Life (QoL). VI. Overall survival (OS). VII. Overall survival rate at 9, 12, and 18 months. VIII. Progression-free survival (PFS). IX. Evaluation of the safety of the DCVax-L + nivolumab combination regimen.
TERTIARY OBJECTIVES:
- Estimate correlation of quantitative assessments of tumor-infiltrating lymphocyte (TIL) proliferation (CD8+/Ki-67+ staining).
II. Estimate difference in PD-1 and PD-L1 immunohistochemistry expression between density or clonality with clinical responses to combination therapy in recurrent glioblastoma subjects.
III. Estimate differences between outcome groups in monocytic PD-L1 expression at baseline and over time.
IV. Estimate differences between outcome groups in circulating tumor DNA, circulating tumor cells, and CD4+ T cells at baseline and over time.
- Estimate difference in PD-1 and PD-L1 immunohistochemical (IHC) expression between archived and study samples.
VI. Explore patterns of tumor proteomic profiling. VII. Estimate efficacy of combination therapy by progression-free survival (PFS), rates of contrasted tumor change over time, and overall survival (OS).
VIII. Explore effect of nivolumab on TIL proliferation (CD8+/Ki-67+ staining). IX. Explore whether oligoclonal T cell populations within tumor tissue are similarly expanded in peripheral blood after nivolumab, the magnitude of which correlates with clinical responses.
- Explore if changes in specific MRI parameters correlate with tumor and peripheral blood immune responses.
XI. Explore if a mesenchymal gene expression signature present in the initial archived tumor sample correlates with T lymphocytic response in tumor after nivolumab.
XII. Correlate changes of positron emission tomography (PET) in tumor with the following: TIL density or clonality, clinical outcome, T cell measures in peripheral blood, clinical toxicity.
XIII. Correlate changes in PET in lymph nodes with the following: TIL density or clonality, clinical outcome, T cell measures in peripheral blood, clinical toxicity.
XIV. Correlate changes in PET in organ tissue with TIL density or clonality.
OUTLINE: Patients are randomized to 1 of 2 groups.
GROUP I: Patients receive dendritic cell-autologous lung tumor vaccine intradermally (ID) on days 0, 7, 14, and weeks 4, 6, 8, 11, 14, 17 and 20.
GROUP II: Patients receive dendritic cell-autologous lung tumor vaccine as in Group I, and nivolumab intravenously (IV) over 30 minutes on days 0, 14, and weeks 4, 6, 8, 11, 14, 17, and 20.
After completion of study treatment, patients are followed up for up to 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group I (DCVax-L) | Experimental | Biological: autologous dendritic cells pulsed with tumor lysate antigen Vaccine, Other: Laboratory Biomarker Analysis, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients receive autologous dendritic cells pulsed with tumor lysate antigen vaccine ID on days 0, 7, 14, and weeks 4, 6, 8, 11, 14, 17 and 20. |
| Group II (DCVax-L, nivolumab) | Experimental | Biological: autologous dendritic cells pulsed with tumor lysate antigen Vaccine, Other: Laboratory Biomarker Analysis, Biological: Nivolumab, Other: Quality-of-Life Assessment, Other: Questionnaire AdministrationPatients receive autologous dendritic cells pulsed with tumor lysate antigen vaccine as in Group I, and nivolumab IV over 30 minutes on days 0, 14, and weeks 4, 6, 8, 11, 14, 17, and 20. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (40 listed)
- PRE-SURGERY SCREENING PROCESS
- Original diagnosis of glioblastoma multiforme (GBM) confirmed by central review
- Radiographic evidence of first recurrence per Response Assessment in Neuro-Oncology (RANO) criteria confirmed by central review
- Surgically accessible, unilateral, recurrent GBM tumor for which extirpative resection, with intent to perform a gross total or near gross total resection, is indicated; a subject may be screened if he or she has had a previous biopsy and is scheduled for a subsequent gross or near gross total resection prior to commencement of other therapies
- Ability to understand and sign the tumor procurement informed consent form indicating awareness of the investigational nature of this study; the consent for tumor tissue donation may be signed by a legally authorized representative (LAR) if allowed by the institution
Key exclusion criteria (32 listed)
- PRE-SCREENING
- Progression on imaging based on RANO criteria within 12 weeks of conclusion of radiotherapy
- History of other prior malignancy except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or other cancers that were deemed fully resolved 5 or more years prior to surgery
- History of active, known, or suspected autoimmune or immunodeficiency disease
- Known human immunodeficiency virus (HIV)-1 or -2 or human T-cell lymphotropic virus (HTLV)-1 or -2 positivity
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 |
|---|---|---|
| autologous dendritic cells pulsed with tumor lysate antigen VaccineAlso: DCVax-LungGiven ID | Biological | Group I (DCVax-L), Group II (DCVax-L, nivolumab) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Group I (DCVax-L), Group II (DCVax-L, nivolumab) |
| NivolumabAlso: BMS-936558, MDX-1106, NIVO, ONO-4538Given IV | Biological | Group II (DCVax-L, nivolumab) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentAncillary studies | Other | Group I (DCVax-L), Group II (DCVax-L, nivolumab) |
| Questionnaire AdministrationAncillary studies | Other | Group I (DCVax-L), Group II (DCVax-L, nivolumab) |
Primary outcome
Incidence of adverse events assessed by National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03
Time frame: Up to 12 months
Will be compared between groups and to those reported for historical standards, including subjects treated with nivolumab in prior trials.
Overall Survival (OS)
Time frame: Up to 12 months
The overall survival curves will be displayed using a Kaplan-Meier curve for the pooled and individual treatments. A one-sample log-rank test will also be completed as a sensitivity analysis for the same survival rate assumption as the primary efficacy analysis, and a two-sample log-rank test will be used to compare the survival distribution between the two arms.
11 secondary outcomes
Overall Survival rate
Time frame: 9 months
Overall Survival rate
Time frame: 12 months
Overall Survival rate
Time frame: 18 months
Progression Free Survival (PFS)
Time frame: From treatment initiation to first progression or death assessed up to 12 months.
Quality of Life (QoL)
Time frame: Up to 12 months
Number of participants with complete response (CR)
Time frame: Up to 12 months of follow up after initiation of treatment
Number of participants with partial response (PR)
Time frame: Up to 12 months of follow up after initiation of treatment
Number of participants with stable disease (SD)
Time frame: Up to 12 months of follow up after initiation of treatment
Number of participants with progressive disease (PD)
Time frame: Up to 12 months of follow up after initiation of treatment
Objective response rate (ORR) defined as the percentage of participants with CR + PR
Time frame: Up to 12 months of follow up after initiation of treatment
Response/Stable Disease Rate (RSDR) defined as the percentage of participants demonstrating CR+PR+SD
Time frame: Up to 12 months of follow up after initiation of treatment
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 Jul 2020.
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HSV G207 in Children With Recurrent or Refractory Cerebellar Brain Tumors
Neoplasms, Brain, Glioblastoma Multiforme
Active, not recruitingPhase 4
Pediatric Long-Term Follow-up and Rollover Study
Diffuse Astrocytoma, Anaplastic Astrocytoma
Active, not recruitingPhase 1
Vorinostat and Temozolomide in Treating Patients With Malignant Gliomas
Adult Anaplastic Astrocytoma, Adult Anaplastic Oligodendroglioma
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.
Timothy Cloughesy 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 2 study testing autologous dendritic cells pulsed with tumor lysate antigen Vaccine, Laboratory Biomarker Analysis and Nivolumab in people with Giant Cell Glioblastoma and Gliosarcoma, 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 40 inclusion and 32 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 Jul 2020. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 assessed by National Cancer Institute's Common Terminology Criteria for Adverse Events version 4.03 (time frame: Up to 12 months). The study lists 2 primary outcomes in all. 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 Jul 2020.