Autologous Dendritic Cells Pulsed With Tumor Lysate Antigen Vaccine and Nivolumab in Treating Patients With Recurrent Glioblastoma

NCT03014804 | Withdrawn Phase 2 DMC FDA Drug

• 2 other identifiers: 16-001706NCI-2016-01587
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Giant Cell Glioblastoma; Gliosarcoma; Oligodendroglioma; Recurrent Glioblastoma; Small Cell Glioblastoma

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 12 months

Secondary Outcomes (11)

• Overall Survival rate

  9 months

• Overall Survival rate

  12 months

• Overall Survival rate

  18 months

• Progression Free Survival (PFS)

  From treatment initiation to first progression or death assessed up to 12 months.

• Quality of Life (QoL)

  Up to 12 months

Other Outcomes (20)

• Changes in PET in lymph nodes

  Baseline up to 12 months

• Changes in PET in organ tissue

  Baseline up to 12 months

• Changes of PET in tumor

  Baseline up to 12 months

Study Arms (2)

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.

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.

Biological: autologous dendritic cells pulsed with tumor lysate antigen Vaccine; Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

autologous dendritic cells pulsed with tumor lysate antigen Vaccine BIOLOGICAL

Given ID

Also known as: DCVax-Lung

Group I (DCVax-L); Group II (DCVax-L, nivolumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Group I (DCVax-L); Group II (DCVax-L, nivolumab)

Nivolumab BIOLOGICAL

Given IV

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

Group II (DCVax-L, nivolumab)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Group I (DCVax-L); Group II (DCVax-L, nivolumab)

Questionnaire Administration OTHER

Ancillary studies

Group I (DCVax-L); Group II (DCVax-L, nivolumab)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Northwest Biotherapeutics: collaborator
• Bristol-Myers Squibb: collaborator
• Brain Tumor Funders Collaborative: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Oligodendroglioma

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Timothy Cloughesy

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2016
• First Posted: January 9, 2017
• Study Start: December 1, 2019
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2022
• Last Updated: July 24, 2020

Record last verified: 2019-08

Locations

US (1)