Nivolumab With DC Vaccines for Recurrent Brain Tumors

NCT02529072 | Completed Phase 1 Results DMC

• 1 other identifier: Pro00065241
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Patients will be randomized to one of two treatment arms - Group I and Group II. Group I will receive nivolumab monotherapy until surgical resection, and Group II will receive nivolumab alone and with DC vaccine therapy until surgical resection. During surgical resection blood and tumor samples will be assessed and compared. Following surgery, both groups will continue to receive DC vaccines (total of 8) and nivolumab therapy until confirmed progression.

Conditions

Malignant Glioma; Astrocytoma; Glioblastoma

Outcome Measures

Primary Outcomes (1)

• The Safety of Administering DC Vaccines With Nivolumab

  The percentage of patients who experience unacceptable toxicity during combination treatment by arm is tabulated. Unacceptable toxicity is defined as any grade 3, 4, or 5 adverse event that is possibly, probably, or definitely related to either nivolumab or DC vaccination treatment during concurrent treatment, or any Grade 2 drug-related uveitis or eye pain or blurred vision that does not respond to topical therapy and does not improve to Grade 1 severity within the re-treatment period OR requires systemic treatment. In addition, any complication following resection (ex. excessive intracranial bleeding, delays in wound healing) that are prolonged longer than 4-6 weeks post-surgery will be considered an unacceptable toxicity.

  12 months

Secondary Outcomes (2)

• Overall Survival

  approximately 4 years from study initiation

• Progression Free Survival (PFS)

  6 to 48 months from study initiation

Study Arms (2)

Group I

EXPERIMENTAL

Patients will receive nivolumab 3 mg/kg IV every 2 weeks for 8 weeks followed by surgery. Following resection, nivolumab and DC vaccine will be administered every 2 weeks (± 1) for a total of 3 vaccines, followed by biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.

Drug: nivolumab; Biological: DC

Group II

EXPERIMENTAL

Patients will initially receive the fourth cycle of nivolumab then receive nivolumab 3 mg/kg IV and DC vaccine every 2 weeks for a total of 3 vaccines, and then surgery. Subsequent to surgery, the patient will resume biweekly treatment with nivolumab and monthly DC vaccinations for a total of 5 more vaccines. Patients will continue to receive nivolumab every 2 weeks until progression.

Drug: nivolumab; Biological: DC

Interventions

nivolumab DRUG

Nivolumab is a fully human monoclonal antibody that targets the programmed death-1 (PD-1) cluster of differentiation 279 cell surface membrane receptor. PD-1 is a negative regulatory molecule expressed by activated T and B lymphocytes. Binding of PD-1 to its ligands, programmed death-ligands 1 and 2, results in the down-regulation of lymphocyte activation. Inhibition of the interaction between PD-1 and its ligands promotes immune responses and antigen-specific T cell responses to both foreign antigens as well as self-antigens. Nivolumab is expressed in Chinese hamster ovary cells and is produced using standard mammalian cell cultivation and chromatographic purification technologies. The clinical study product is a sterile solution for parenteral administration.

Also known as: BMS-936558, MDX1106

Group I; Group II

DC BIOLOGICAL

DCs are potent immunostimulatory cells that continuously sample the antigenic environment of the host and specifically activate cluster of differentiation 4 positive (CD4+) and cluster of differentiation 8 positive (CD8+) T-cells and B-cells. They are at the crossroads of many of the elegant networks of the immune system, and DCs represent the most promising contemporary biologic entity for realizing the promise of immunotherapy. Potent immune responses and encouraging clinical results have been seen in Phase I and II human clinical trials in systemic cancers. Numerous animal studies and the investigator's institution's humans studies have demonstrated potent antitumor responses using DC-based immunotherapy against MGs.

Also known as: DC vaccine, pp65 DC vaccine, Human CMV pp65-LAMP mRNA-pulsed autologous DCs, CMV pp65 DCs

Group I; Group II

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-80 years of age
• First or second recurrence of MG (WHO Grade III or IV glioma or astrocytoma) in surgically accessible areas with prior histologic diagnosis of MG
• Bevacizumab-naïve - no prior exposure to Bevacizumab
• Karnofsky Performance Status (KPS) of ≥ 70%
• Radiation Therapy (RT) with ≥ 45 Gray (Gy) tumor dose, completed ≥ 8 weeks prior to study entry
• Laboratory values must meet the following criteria:
• White Blood Count (WBC) ≥ 2000/microliters (uL)
• Neutrophils ≥ 1500/uL
• Platelets ≥ 100x103/uL
• Hemoglobin ≥ 9.0 g/dL
• Serum creatinine ≤ 1.5x the upper limit of normal (ULN) or creatinine clearance (CrCl)≥ 40 mL/min (using the Cockcroft-Gault formula) c. Female CrCl = (140 - age in years) x weight in kg x 0.85 /72 x serum creatinine in mg/dL d. Male CrCl = (140 - age in years) x weight in kg x 1.00/72 x serum creatinine in mg/dL
• Aspartate Aminotransferase (AST) ≤ 3x ULN
• Alanine Aminotransferase (ALT) ≤ 3x ULN
• Bilirubin≤ 1.5x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin \< 3.0 mg/dL)
• Subjects must have resting baseline O2 saturation by pulse oximetry of ≥ 92% at rest.

You may not qualify if:

• Contrast-enhancing tumor component crossing the midline, multi-focal tumor, or tumor dissemination (subependymal or leptomeningeal)
• Clinically significant increased intracranial pressure (e.g., impending herniation), uncontrolled seizures, or requirement for immediate palliative treatment
• Pregnant or need to breast feed during the study period (Negative human chorionic gonadotropin (β-HCG) test required), or unable to maintain use of contraception while on study and for 31 weeks after the last dose of nivolumab
• Active infection requiring treatment or an unexplained febrile (\> 101.5o F) illness
• Known immunosuppressive disease, autoimmune disease or human immunodeficiency virus infection, Hepatitis B or Hepatitis C
• Known allergy or hypersensitivity to tetanus, or any other tetanus or diphtheria toxoid-containing vaccine, or any component of this vaccine (i.e., aluminum phosphate, formaldehyde)
• Known severe (Grade 3 or 4) infusion-related allergy or hypersensitivity to any monoclonal antibody
• Previous radiation therapy with anything other than standard radiation therapy (such as previous stereotactic radiosurgery) or previous treatment with an immune checkpoint inhibitor (i.e., nivolumab, pembrolizumab, ipilimumab)
• Unstable or severe intercurrent medical conditions such as severe heart (New York Association Class 3 or 4) or lung (FEV1 \< 50%) disease, uncontrolled diabetes mellitus
• Corticosteroid use \> 4 mg/day at time of consent
• Prior inguinal lymph node dissection.

Sponsors & Collaborators

• Gary Archer Ph.D.: lead
• Bristol-Myers Squibb: collaborator
• Duke Cancer Institute: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Glioma; Astrocytoma; Glioblastoma

Interventions

Nivolumab; lentiviral minigene vaccine of COVID-19 coronavirus

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Principal Investigator
• Organization: Duke University Medical Center

dukebrain1@duke.edu

9196845301

Study Officials

• Katherine Peters, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 12, 2015
• First Posted: August 19, 2015
• Study Start: January 1, 2016
• Primary Completion: September 15, 2017
• Study Completion: December 30, 2019
• Last Updated: March 26, 2020
• Results First Posted: March 26, 2020

Record last verified: 2020-03

Locations

US (1)