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

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ClinicalTrials.gov Identifier: NCT02465268
Recruitment Status : Recruiting
First Posted : June 8, 2015
Last Update Posted : November 23, 2020
Sponsor:
Collaborators:
University of Florida
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Immunomic Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE May 27, 2015
First Posted Date  ICMJE June 8, 2015
Last Update Posted Date November 23, 2020
Study Start Date  ICMJE August 2016
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 3, 2015)
Change in median overall survival [ Time Frame: From date of randomization until the date of death, assessed up to 24 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 26, 2016)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: June 3, 2015)
  • Migration of dendritic cells to vaccine draining lymph nodes [ Time Frame: Level of uptake approximately 1 month after randomization ]
  • Changes in peripheral blood and PBMC immune response [ Time Frame: Change between baseline and approximately 1 month after randomization ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vaccine Therapy for the Treatment of Newly Diagnosed Glioblastoma Multiforme
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE
  • Glioblastoma Multiforme
  • Glioblastoma
  • Malignant Glioma
  • Astrocytoma, Grade IV
  • GBM
Intervention  ICMJE
  • Biological: pp65-shLAMP DC with GM-CSF
    Other Name: pp65-shLAMP mRNA DCs with GM-CSF
  • Biological: unpulsed PBMC and saline
    Other Name: Peripheral Blood Mononuclear Cells
  • 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: Saline
    Other Name: Normal Saline
  • Biological: pp65-flLAMP DC with GM-CSF
    Other Name: pp65-flLAMP mRNA DCs with GM-CSF
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: pp65-shLAMP DC with GM-CSF
    • Drug: Td
  • 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.
    Interventions:
    • Drug: Td
    • Biological: pp65-flLAMP DC 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.
    Interventions:
    • Biological: unpulsed PBMC and saline
    • Drug: Saline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 3, 2019)
120
Original Estimated Enrollment  ICMJE
 (submitted: June 3, 2015)
150
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Abbreviated 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.

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 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Nina McGrew, MSN 352-273-5519 nina.mcgrew@neurosurgery.ufl.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02465268
Other Study ID Numbers  ICMJE IRB201400697-N
R01CA175517 ( U.S. NIH Grant/Contract )
OCR14127 ( Other Identifier: Universiy of Florida )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Immunomic Therapeutics, Inc.
Study Sponsor  ICMJE Immunomic Therapeutics, Inc.
Collaborators  ICMJE
  • University of Florida
  • National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Duane Mitchell, MD, PhD University of Florida
Principal Investigator: Maryam Rahman, MD University of Florida
PRS Account Immunomic Therapeutics, Inc.
Verification Date November 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP