Vaccine Therapy for the Treatment of Newly Diagnosed Glioblastoma Multiforme

NCT02465268 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB201400697-NR01CA175517OCR14127
• Study Type: interventional
• Target: 175
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this research study is to determine if an investigational dendritic cell vaccine, called pp65 DC, is effective for the treatment of a specific type of brain tumor called glioblastoma (GBM) when given with stronger doses of routine chemotherapy.

Conditions

Glioblastoma Multiforme; Glioblastoma; Malignant Glioma; Astrocytoma, Grade IV; GBM

Outcome Measures

Primary Outcomes (1)

• Comparison of Overall Survival (OS) Between the Active Treatment Group (Arms 1 and 2) and the Control Group (Arm 3)

  Kaplan-Meier survival curves and the log rank test will be used to characterize and compare OS in patients who received pp65-LAMP mRNA DC vaccine (Arms 1 and 2) and in control patients (Arm 3). OS will be defined as the time between first vaccination and death and will be censored at the last follow-up if death has not occurred.

  From date of first vaccine until the date of death, up to 48 months

Secondary Outcomes (7)

• Comparison of Progression-free Survival Between the Active Treatment Group (Arms 1 and 2 Combined) and the Control Group (Arm 3)

  From date of first vaccine until time disease progression or death without prior progression/recurrence, up to 48 months

• ELISPOT Assay (pp65)

  baseline, post-vaccine #3

• Flow Cytometric Analysis (T Cell)

  baseline, post-vaccine #3

• Cytokine Array Analysis (IFN-g)

  baseline, post-vaccine #3

• ELISPOT Assay (Actin)

  baseline, post-vaccine #3

Study Arms (3)

Arm 1: pp65-shLAMP DC with GM-CSF and Td

EXPERIMENTAL

Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.

Biological: pp65-shLAMP DC with GM-CSF; Drug: Td

Arm 2: pp65-flLAMP DC with GM-CSF and Td

EXPERIMENTAL

Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.

Drug: Td; Biological: pp65-flLAMP DC with GM-CSF

Arm 3: unpulsed PBMC and Saline

PLACEBO COMPARATOR

Given under the skin at day 22-24 after the first temozolomide cycle then at 2 week intervals. Doses 4-10 will be given on day 22-24 of each temozolomide cycle. Doses will continue until a total of 10 or until progression or unacceptable toxicity.

Biological: unpulsed PBMC and saline; Drug: Saline

Interventions

pp65-shLAMP DC with GM-CSF BIOLOGICAL

Also known as: pp65-shLAMP mRNA DCs with GM-CSF

Arm 1: pp65-shLAMP DC with GM-CSF and Td

unpulsed PBMC and saline BIOLOGICAL

Also known as: Peripheral Blood Mononuclear Cells

Arm 3: unpulsed PBMC and Saline

Td DRUG

All subjects will receive a Td booster before study drug dose #1. Subjects in the experimental arms will receive Td skin prep before study drug doses #3, #6, and #9.

Also known as: Tetanus and Diphtheria Toxoid

Arm 1: pp65-shLAMP DC with GM-CSF and Td; Arm 2: pp65-flLAMP DC with GM-CSF and Td

Saline DRUG

Also known as: Normal Saline

Arm 3: unpulsed PBMC and Saline

pp65-flLAMP DC with GM-CSF BIOLOGICAL

Also known as: pp65-flLAMP mRNA DCs with GM-CSF

Arm 2: pp65-flLAMP DC with GM-CSF and Td

Eligibility Criteria

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

You may qualify if:

• To be assessed at study enrollment prior to standard of care chemo-radiation therapy:
• Age ≥ 18 years.
• Histopathologically proven newly-diagnosed de novo GBM (WHO Grade IV glioma)
• The tumor must have a supratentorial component.
• Must have undergone definitive surgical resection of tumor with less than approximately 3cm x 3cm residual enhancing tumor as product of longest perpendicular planes by MRI.
• Recovery from the effects of surgery, postoperative infection, and other complications.
• Diagnostic contrast-enhanced MRI or CT scan of the brain preoperatively and postoperatively.
• Karnofsky Performance Status of ≥ 70.
• Signed informed consent.
• For females of childbearing potential, negative serum pregnancy test.
• Women of childbearing potential and male participants must be willing to practice adequate contraception throughout the study and for at least 24 weeks after the last dose of study drug.
• To be assessed prior to initiation of adjuvant TMZ:
• Must have completed RT (targeted total dose of 59.4-60.0 Gy over ≤ 7 weeks) and concomitant TMZ (targeted dose of 75mg/m2/d for ≤ 49 days) therapy without significant toxicity that persisted over 4 weeks.
• History \& physical with neurologic examination prior to initiation of adjuvant TMZ.
• For patients receiving steroids, daily dose must be ≤ 4 mg.

You may not qualify if:

• To be verified in order to randomize subject:
• Prior invasive malignancy unless disease free for ≥ 3 years.
• Metastases detected below the tentorium or beyond the cranial vault and leptomeningeal involvement.
• Recurrent or multifocal malignant gliomas.
• HIV, Hepatitis B, or Hepatitis C seropositive.
• Known active infection or immunosuppressive disease.
• Prior chemotherapy or radiosensitizers (including Gliadel wafers) for cancers of the head and neck region.
• Prior radiotherapy to the head or neck, resulting in overlap of radiation fields.
• Severe, active co-morbidity.
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception for the entire study period.
• Pregnant or lactating women.
• Prior allergic reaction to temozolomide, GM-CSF or Td.
• Prior history of brachial neuritis or Guillain-Barré syndrome.
• Patients treated on any other therapeutic clinical protocols within 30 days prior to study entry.
• To be assessed prior to initiation of adjuvant TMZ:

Sponsors & Collaborators

• University of Florida: lead
• National Cancer Institute (NCI): collaborator

Study Sites (3)

University of Florida

Gainesville, Florida, 32610, United States

Location

Orlando Health

Orlando, Florida, 32806, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Glioblastoma; Glioma

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; Sodium Chloride; Tetanus Toxoid; Diphtheria Toxoid; Saline Solution

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Toxoids; Vaccines; Biological Products; Complex Mixtures; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Duane Mitchell, MD, PhD
• Organization: University of Florida

duane.mitchell@neurosurgery.ufl.edu

352-273-9000

Study Officials

• Duane Mitchell, MD, PhD

  University of Florida

  STUDY CHAIR

• Maryam Rahman, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2015
• First Posted: June 8, 2015
• Study Start: August 9, 2016
• Primary Completion: November 30, 2023
• Study Completion: November 30, 2023
• Last Updated: January 14, 2025
• Results First Posted: January 14, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)