Phase II Feasibility Study of Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT00323115
First received: May 4, 2006
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme will be treated with radiotherapy/chemotherapy followed by dendritic cell vaccine. Chemotherapy will be administered after three vaccinations for one year or until progression of disease.


Condition Intervention Phase
Glioblastoma Multiforme
Biological: Autologous Dendritic Cell
Drug: Temozolomide
Procedure: Radiotherapy
Biological: Dendritic Cell Vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Feasibility Study of Adjuvant Intra-Nodal Autologous Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Dartmouth-Hitchcock Medical Center:

Primary Outcome Measures:
  • Tumor-specific Cytotoxic T-cell Response [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    MRI & pheresis post vaccine


Secondary Outcome Measures:
  • Feasibility and Toxicity Profile of Intra-nodal DC/Tumor Lysate Vaccination [ Time Frame: Pheresis ] [ Designated as safety issue: Yes ]
  • Progression Free Survival (PFS)and Overall Survival (OS) Comparison to Prognostic Matched Historical Controls [ Time Frame: From Enrollment - March 2011 ] [ Designated as safety issue: No ]
    PFS will be assessed for each patient as the time from surgery until the patient reaches objective disease progression by MRI, defined as greater than or equal to a 25% increase in the product of the largest perpendicular diameters of contrast enhancement of any lesion or any new enhancing tumor on MRI or CT scans.

  • Immunological Parameters With PFS vs Overall Survival [ Time Frame: Evaluable patients for immunologic parameters are those who have completed 3 vaccines ] [ Designated as safety issue: No ]
  • Radiological Response When There is Residual Enhancing Tumor at Baseline MRI [ Time Frame: MRI post vaccine ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: May 2006
Study Completion Date: July 2013
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccine Biological: Autologous Dendritic Cell
Vaccine given by cervical lymph node injection 3 times every other week
Drug: Temozolomide
Radiotherapy (RT) with concurrent temozolomide (TMZ) for 6 weeks before vaccine is SOC
Procedure: Radiotherapy
RT is standard of care (SOC) post surgery
Biological: Dendritic Cell Vaccine
Vaccine given cervical lymphnode injection 3 times every other week

Detailed Description:

Two to six weeks after surgery, patients with newly diagnosed glioblastoma multiforme (GBM) will undergo a six-week course of radiotherapy with concurrent chemotherapy (temozolomide). Between three and seven weeks after completing radiotherapy/chemotherapy, patients will undergo leukapheresis to collect white blood cells. These cells will be grown into dendritic cells, and cultured with tumor cells from the individual patient. Vaccinations will be given every two weeks for a total of three vaccinations. Four weeks after the third vaccination patients will resume chemotherapy for one year or until disease progression.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically proven GBM with central pathology review at Dartmouth-Hitchcock Medical Center (DHMC)
  • Tumor specimen obtained at the time of surgery adequate for vaccination
  • 18 years of age or older
  • Karnofsky Performance Status 60% or greater
  • Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10 9th/L
  • Platelets greater than or equal to 100 x 10 9th/L
  • Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) less than or equal to 5 times the upper limits of normal (ULN)
  • Total bilirubin less than or equal to 1.5 times ULN
  • Serum creatinine less than or equal to 1.5 times ULN, OR estimated creatinine clearance greater than or equal to 60 mL/min
  • No known immunosuppression other than chemo-related
  • Negative HIV serologies
  • No evidence of acute or chronic hepatitis on standard hepatitis C and B screening tests
  • No chemotherapy within four weeks prior to leukapheresis
  • Radiotherapy at outside institution is permitted if tissue was obtained at time of surgery at DHMC and patient is willing to follow-up per protocol
  • Off steroids for at least two weeks before leukapheresis
  • No second malignancies except non-melanoma skin cancer, and non-invasive cancer such at cervical CIS, superficial bladder cancer or breast CIS
  • Negative serum or urine pregnancy test for women of childbearing potential
  • No serious uncontrolled medical disorder or active infection
  • All patients must give informed consent
  • No history of clinical evidence of active autoimmune disease

Exclusion Criteria:

  • Invasive cancers in the past 5 years
  • Rheumatologic/autoimmune disease
  • Pregnancy or unwillingness to remain on acceptable form of birth control during study
  • Major cardiac, pulmonary, or other systemic disease; viral hepatitis; HIV infection
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00323115

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
Sponsors and Collaborators
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: Camilo E. Fadul, MD Dartmouth-Hitchcock Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier: NCT00323115     History of Changes
Other Study ID Numbers: D0536
Study First Received: May 4, 2006
Results First Received: August 24, 2012
Last Updated: June 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Dartmouth-Hitchcock Medical Center:
immunotherapy
cancer vaccine
glioblastoma multiforme

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
Temozolomide
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 28, 2014