Vaccine Therapy for the Treatment of Newly Diagnosed Glioblastoma Multiforme

NCT ID: NCT02465268

Last Updated: 2025-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 175 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-09
• Study Completion Date: 2023-11-30

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.

Detailed Description

Dendritic cells (DC) are involved in activating, or turning-on, your body's immune system. Your immune system helps guard your body from germs, viruses, and other threats. Although dendritic cells are very strong, the number of them in the body is not high enough to cause a powerful immune response; therefore, more DC are made in a laboratory with cells collected from an individual's blood.

In this study, we will make a vaccine that we hope will educate immune cells to target the pp65 antigen, a type of immune marker in GBM, thus resulting in what we call the pp65 DC vaccine. Use of a vaccine that activates your immune system is a type of immunotherapy. It is hoped that by giving the pp65 DC vaccine as a shot under the skin, the immune system will be activated to attack tumor cells in the brain while leaving normal cells alone.

To see if the pp65 DC vaccine is effective for the treatment of GBM, subjects will be assigned to different treatment groups. Two groups of subjects will receive the pp65 DC vaccine and one group will receive a placebo.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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

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.

Group Type: EXPERIMENTAL

pp65-shLAMP DC with GM-CSF

Intervention Type: BIOLOGICAL

Td

Intervention Type: 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.

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

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.

Group Type: EXPERIMENTAL

Td

Intervention Type: 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.

pp65-flLAMP DC with GM-CSF

Intervention Type: BIOLOGICAL

Arm 3: unpulsed PBMC and Saline

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.

Group Type: PLACEBO_COMPARATOR

unpulsed PBMC and saline

Intervention Type: BIOLOGICAL

Saline

Intervention Type: DRUG

Interventions

pp65-shLAMP DC with GM-CSF

Intervention Type: BIOLOGICAL

unpulsed PBMC and saline

Intervention Type: BIOLOGICAL

Td

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.

Intervention Type: DRUG

Saline

Intervention Type: DRUG

pp65-flLAMP DC with GM-CSF

Intervention Type: BIOLOGICAL

Other Intervention Names

pp65-shLAMP mRNA DCs with GM-CSF; Peripheral Blood Mononuclear Cells; Tetanus and Diphtheria Toxoid; Normal Saline; pp65-flLAMP mRNA DCs with GM-CSF

Eligibility Criteria

Inclusion Criteria

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.
• CBC with differential with adequate bone marrow function.
• Adequate renal function.
• Adequate hepatic function.

Exclusion Criteria

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:

• Did not start radiation therapy and temozolomide within 7 weeks of surgery.
• Progression of disease as defined by modified RANO criteria.
• More than 45 days after completion of radiation therapy and temozolomide

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Duane Mitchell, MD, PhD

Role: STUDY_CHAIR

University of Florida

Maryam Rahman, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

University of Florida

Gainesville, Florida, United States

Orlando Health

Orlando, Florida, United States

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

R01CA175517

Identifier Type: NIH

Identifier Source: secondary_id

View Link

OCR14127

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201400697-N

Identifier Type: -

Identifier Source: org_study_id