Clinical trial NCT00323115: Phase II Feasibility Study of Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme
Official title: A Phase II Feasibility Study of Adjuvant Intra-Nodal Autologous Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: immunotherapy
cancer vaccine
glioblastoma multiforme
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
First posted: 2006-05-09
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Tumor-specific Cytotoxic T-cell Response
timeFrame: Day 42
Secondary outcomes:
measure: Number of Adverse Events: Toxicity Profile of Intra-nodal DC/Tumor Lysate Vaccination
timeFrame: Until death or approximately 24 months after diagnosis
measure: Number of Participants With Evaluable Data: Feasibility of Vaccination
timeFrame: Through enrollment, approximately 2 years
measure: Progression Free Survival (PFS)
timeFrame: Approximately 42 months
measure: Number of Participants With Significant Difference in Tumor Volume Size Pre- and Postvaccination: Neuroimaging and Tumor Assessment
timeFrame: baseline and 4 weeks
measure: Overall Survival Duration: Efficacy Parameters
timeFrame: Approximately 42 months
measure: Frequency of CD4+ and CD8+ T Cells - the Proportion of Cells in the Parent Population Responding to Glioblastoma Multiforme (GBM) - Median
timeFrame: Day 7 (pre-vaccination) and Day 42 (post-vaccination).
measure: Percentage of Tumor-specific T-cells - Correlation Between Immunological Parameters and Efficacy- Median
timeFrame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
measure: Number of Enzyme-linked Immunosorbent Spots (ELISPOT) - Correlation Between Immunological Parameters and Efficacy - Median
timeFrame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
measure: Frequency of CD4+ and CD8+ T Cells - the Proportion of Cells in the Parent Population Responding to Glioblastoma Multiforme (GBM) - Mean
timeFrame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
measure: Percentage of Tumor-specific T-cells - Correlation Between Immunological Parameters and Efficacy- Mean
timeFrame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
measure: Number of Enzyme-linked Immunosorbent Spots (ELISPOT) - Correlation Between Immunological Parameters and Efficacy - Mean
timeFrame: Day 7 (pre-vaccination) and Day 42 (post-vaccination)
measure: Evaluation of T Cell Characteristics
timeFrame: Before starting radiation/Temozolomide and at Day 7 and Day 42.
measure: Immunohistochemistry
timeFrame: Approximately 42 months
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Dartmouth-Hitchcock Medical Center
name: Camilo E. Fadul, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fadul CE, Fisher JL, Hampton TH, Lallana EC, Li Z, Gui J, Szczepiorkowski ZM, Tosteson TD, Rhodes CH, Wishart HA, Lewis LD, Ernstoff MS. Immune response in patients with newly diagnosed glioblastoma multiforme treated with intranodal autologous tumor lysate-dendritic cell vaccination after radiation chemotherapy. J Immunother. 2011 May;34(4):382-9. doi: 10.1097/CJI.0b013e318215e300.