We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

Vaccine Therapy for the Treatment of Newly Diagnosed Glioblastoma Multiforme (ATTAC-II)

This study is currently recruiting participants.
Verified September 2017 by University of Florida
Sponsor:
ClinicalTrials.gov Identifier:
NCT02465268
First Posted: June 8, 2015
Last Update Posted: September 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
University of Florida
  Purpose
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.

Condition Intervention Phase
Glioblastoma Multiforme Glioblastoma Malignant Glioma Astrocytoma, Grade IV GBM Biological: pp65-shLAMP DC with GM-CSF Biological: unpulsed PBMC and saline Drug: Td Drug: Saline Drug: pp65-flLAMP DC with GM-CSF Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Phase II Randomized, Blinded, and Placebo-controlled Trial of CMV RNA-Pulsed Dendritic Cells With Tetanus-Diphtheria Toxoid Vaccine in Patients With Newly-Diagnosed Glioblastoma

Resource links provided by NLM:


Further study details as provided by University of Florida:

Primary Outcome Measures:
  • Change in median overall survival [ Time Frame: From date of randomization until the date of death, assessed up to 24 months ]

Secondary Outcome Measures:
  • Changes in immune response [ Time Frame: Change between baseline and vaccine #3, assessed up to 4 weeks ]
    Parameters include ELISPOT for evaluation of cellular immune responses is a sensitive detection assay for evaluation of antigen specific cytokine producing T cells

  • Change in progression-free survival [ Time Frame: From randomization until first documentation of either disease progression or recurrence assessed up to 24 months ]
  • Changes in immune response [ Time Frame: Change between baseline and vaccine #3, assessed up to 4 weeks ]
    Parameters include peak antibody titers to the CMV pp65, reported as humoral response to the specific antigens.

  • Changes in immune response [ Time Frame: Change between baseline and vaccine #3, assessed up to 4 weeks ]
    Parameters include Cytokine Bead Array analysis to detect multiple cytokines secreted by lymphocytes after in vitro stimulation with specific and control antigens, examine the spectrum of Type 0,1,2, and 3 cytokines secreted by T cells after stimulation with overlapping peptides spanning CMV pp65, PHA, and control peptides

  • Changes in immune response [ Time Frame: Change between baseline and vaccine #3, assessed up to 4 weeks ]
    Parameters include cytokine flow cytometric analysis which involves the rapid early detection and analysis of the production of IFN, TNF, and IL-2 prior to cellular secretion following antigen-specific stimulation in vitro as determined by CFC


Estimated Enrollment: 150
Study Start Date: August 2016
Estimated Study Completion Date: June 2024
Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: pp65-shLAMP DC with GM-CSF
Other Name: pp65-shLAMP mRNA DCs with GM-CSF
Drug: 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.
Other Name: Tetanus and Diphtheria Toxoid
Experimental: 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.
Drug: 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.
Other Name: Tetanus and Diphtheria Toxoid
Drug: pp65-flLAMP DC with GM-CSF
Other Name: pp65-flLAMP mRNA DCs with GM-CSF
Placebo Comparator: 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.
Biological: unpulsed PBMC and saline
Other Name: Peripheral Blood Mononuclear Cells
Drug: Saline
Other Name: Normal Saline

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Abbreviated Inclusion Criteria:

To be assessed at study enrollment prior to 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.

To be assessed prior to initiation of adjuvant TMZ:

  • Must have completed RT (60Gy over 6 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.

Abbreviated 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.
  • 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 iRANO criteria.
  • More than 45 days after completion of radiation therapy and temozolomide
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02465268


Contacts
Contact: Nina McGrew, MSN 352-273-5519 nina.mcgrew@neurosurgery.ufl.edu

Locations
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Phuong Deleyrolle, RN    352-273-5529    phuong.deleyrolle@neurosurgery.ufl.edu   
Principal Investigator: Maryam Rahman, MD         
Orlando Health Recruiting
Orlando, Florida, United States, 32806
Contact: Robert Ferry, B.S.    321-841-1077    Robert.Ferry@orlandohealth.com   
Principal Investigator: Nicholas Avgeropoulos, M.D.         
United States, North Carolina
Duke University Medical Center Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Katherine Peters, MD, PhD    919-684-5301    dukebrain1@dm.duke.edu   
Contact: Stevie Threatt    919-684-5301    dukebrain1@dm.duke.edu   
Sponsors and Collaborators
University of Florida
National Cancer Institute (NCI)
Investigators
Study Chair: Duane Mitchell, MD, PhD University of Florida
  More Information

Responsible Party: University of Florida
ClinicalTrials.gov Identifier: NCT02465268     History of Changes
Other Study ID Numbers: IRB201400697
R01CA175517 ( U.S. NIH Grant/Contract )
First Submitted: May 27, 2015
First Posted: June 8, 2015
Last Update Posted: September 29, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue