Trial Outcomes & Findings for Phase II Feasibility Study of Dendritic Cell Vaccination for Newly Diagnosed Glioblastoma Multiforme (NCT NCT00323115)

Results Overview

MRI \& pheresis post vaccine

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

11 participants

Primary outcome timeframe

Day 42

Results posted on

2018-10-10

Participant Flow

Between May 2006 and February 2008, 60 patients were diagnosed with GBM at our institution. Of 11 patients who entered the study, 1 had a seizure with neurologic deterioration several weeks after leukapheresis and did not receive any DC vaccinations.

Participant milestones

Participant milestones
Measure	Vaccine Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression
Vaccine Administration STARTED	11
Vaccine Administration COMPLETED	10
Vaccine Administration NOT COMPLETED	1
Adjuvant Therapy & Survival Follow-Up STARTED	10
Adjuvant Therapy & Survival Follow-Up COMPLETED	2
Adjuvant Therapy & Survival Follow-Up NOT COMPLETED	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Vaccine Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression
Vaccine Administration Adverse Event	1
Adjuvant Therapy & Survival Follow-Up Death	8

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vaccine n=11 Participants Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants
Age, Continuous	63.273 years STANDARD_DEVIATION 9.53 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Region of Enrollment United States	11 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 42

Population: All participants who received all 3 vaccine administrations were used in this data analysis.

MRI \& pheresis post vaccine

Outcome measures

Outcome measures
Measure	Vaccine n=10 Participants Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression	Post-Vaccine Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week	Vaccine - Second Leukapheresis Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression
Tumor-specific Cytotoxic T-cell Response No. CD8+	0.4836 10^9 cells/L Interval 0.135 to 0.976	—	—
Tumor-specific Cytotoxic T-cell Response No. CD4+	0.496 10^9 cells/L Interval 0.198 to 0.921	—	—

SECONDARY outcome

Timeframe: Until death or approximately 24 months after diagnosis

Population: Participants were monitored for adverse events at each visit and observed for 2 hours after intranodal injections. Toxicities were graded using the Common Terminology Criteria for Adverse Events (version 3.0) and Common Toxicity Criteria (version 3.0).

Adverse events attributed to vaccination. Collected and attributed adverse events at each study visit; monitored participants for adverse events for two hours following vaccination procedure.

Outcome measures

Outcome measures
Measure	Vaccine n=10 Participants Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression	Post-Vaccine Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week	Vaccine - Second Leukapheresis Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression
Number of Adverse Events: Toxicity Profile of Intra-nodal DC/Tumor Lysate Vaccination	1 attributable adverse events	—	—

SECONDARY outcome

Timeframe: Through enrollment, approximately 2 years

To determine the feasibility of this approach, the investigators hypothesize that at least 2/3 of the patients included in the study will be evaluable, meaning that the participants would have received the 3 vaccinations with immunologic outcome parameters measured before and after vaccination. Therefore a maximum of 15 patients would be enrolled in the study to obtain 10 evaluable patients. If after enrolling 15 patients the investigators are unable to obtain 10 evaluable patients, the investigators would consider this approach not feasible.

Outcome measures

Outcome measures
Measure	Vaccine n=10 Participants Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression	Post-Vaccine Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week	Vaccine - Second Leukapheresis Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression
Number of Participants With Evaluable Data: Feasibility of Vaccination	10 Participants	—	—

SECONDARY outcome

Timeframe: Approximately 42 months

Progression-free survival will be assessed for each patient as the time from surgery until the patient reaches objective disease progression by MRI criteria. Death will be regarded as a progression event in those patients that die before disease progression. Patients without documented objective progression at the time of the analysis will be censored at the date of their last objective tumor assessment. Since disease free survival and overall survival are secondary endpoints all patients will be followed until death or for a period of 5 years following enrollment.

Outcome measures

Outcome measures
Measure	Vaccine n=10 Participants Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression	Post-Vaccine Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week	Vaccine - Second Leukapheresis Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression
Progression Free Survival (PFS)	9.5 Months Interval 5.0 to 41.0	—	—

SECONDARY outcome

Timeframe: baseline and 4 weeks

Patients with evidence of evaluable enhancing disease on contrast-enhanced MRI performed within four weeks of study entry will be evaluated for response rate. Patients will be evaluated for objective tumor assessments by gadolinium-enhanced magnetic resonance imaging (Gd-MRI). Comparisons of objective assessments, excluding progressive disease, are based upon major changes in tumor size on the Gd-MRI compared to the baseline scan. Determination of progressive disease is based upon comparison to the previous scan with volumetric analysis.

Outcome measures

Outcome measures
Measure	Vaccine n=10 Participants Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression	Post-Vaccine Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week	Vaccine - Second Leukapheresis Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression
Number of Participants With Significant Difference in Tumor Volume Size Pre- and Postvaccination: Neuroimaging and Tumor Assessment	0 Participants	—	—

SECONDARY outcome

Timeframe: Approximately 42 months

Population: There were 4 patients alive when data collection ended, including the patient the longest overall survival.

Overall survival will also be followed. Survival will be assessed from the date of surgery to the date of patient death, due to any cause, or to the last date the patient was known to be alive.

Outcome measures

Outcome measures
Measure	Vaccine n=10 Participants Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression	Post-Vaccine Dendritic Cell Vaccine: Vaccine given cervical lymphnode injection 3 times every other week	Vaccine - Second Leukapheresis Adult patients who have surgical resection of newly diagnosed glioblastoma multiforme (GBM) will be treated with radiotherapy and concurrent chemotherapy followed by intranodal vaccine with autologous dendritic cells (DCs) primed with tumor lysate. Adjuvant chemotherapy will be administered after vaccination for 1 year or until tumor progression
Overall Survival Duration: Efficacy Parameters	28 Months Interval 15.0 to 44.0	—	—

SECONDARY outcome

Timeframe: Day 7 (pre-vaccination) and Day 42 (post-vaccination).

Population: proportion of cells responding to GBM; GBM = glioblastoma multiforme

Pre- and post-vaccine immune assay results (Tumor-specific T-cells ) are summarized on a continuous scale as median.