Trial Outcomes & Findings for Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme (NCT NCT00643097)

Last Updated: 2017-02-01

Results Overview

Number of patients that developed a delayed-type hypersensitivity (DTH) response at following vaccination. Any skin reaction in response to the intradermal injection of the antigen was measured and recorded. A positive skin test was defined as \> 5 mm induration (swelling).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

40 participants

Primary outcome timeframe

26 months

Results posted on

2017-02-01

Participant Flow

Participant milestones

Participant milestones
Measure	Arm I (ACTIVATE) Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) every 2 weeks starting 4 weeks after the completion of radiation. Subsequent vaccinations were given once a month until clinical or radiographic evidence of progression or death.	Arm II (ACT II STD) Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 200 mg/m2 for the first 5 days of a 28 day cycle.	Arm III (ACT II DI) Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 100 mg/m2 for the first 21 days of a 28 day cycle.
Overall Study STARTED	18	12	10
Overall Study COMPLETED	18	12	10
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vaccine Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm I (ACTIVATE) n=18 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) every 2 weeks starting 4 weeks after the completion of radiation. Subsequent vaccinations were given once a month until clinical or radiographic evidence of progression or death.	Arm II (ACT II STD) n=12 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 200 mg/m2 for the first 5 days of a 28 day cycle.	Arm III (ACT II DI) n=10 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 100 mg/m2 for the first 21 days of a 28 day cycle.	Total n=40 Participants Total of all reporting groups
Age, Continuous	52 years n=5 Participants	57 years n=7 Participants	59 years n=5 Participants	53 years n=4 Participants
Gender Female	5 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Gender Male	13 Participants n=5 Participants	11 Participants n=7 Participants	6 Participants n=5 Participants	30 Participants n=4 Participants

PRIMARY outcome

Timeframe: 26 months

Population: The test was performed on a subset of patients in each group that were available at vaccine 8, and results posted for those 30 patients who had the tests performed.

Outcome measures

Outcome measures
Measure	Arm I (ACTIVATE) n=17 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) every 2 weeks starting 4 weeks after the completion of radiation. Subsequent vaccinations were given once a month until clinical or radiographic evidence of progression or death.	Arm II (ACT II STD) n=5 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 200 mg/m2 for the first 5 days of a 28 day cycle.	Arm III (ACT II DI) n=8 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 100 mg/m2 for the first 21 days of a 28 day cycle.
Humoral and Cellular Immune Response	3 participants	0 participants	7 participants

PRIMARY outcome

Timeframe: 58 months

Time in months from the start of study treatment to the date of first progression according to Macdonald criteria, or to death due to any cause. Patients alive who had not progressed as of the last follow-up had PFS censored at the last follow-up date. Median PFS was estimated using a Kaplan-Meier curve. Macdonald criteria are standard criteria in neuro-oncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of: 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).

Outcome measures

Outcome measures
Measure	Arm I (ACTIVATE) n=18 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) every 2 weeks starting 4 weeks after the completion of radiation. Subsequent vaccinations were given once a month until clinical or radiographic evidence of progression or death.	Arm II (ACT II STD) n=12 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 200 mg/m2 for the first 5 days of a 28 day cycle.	Arm III (ACT II DI) n=10 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 100 mg/m2 for the first 21 days of a 28 day cycle.
Clinical Efficacy of Vaccination, in Terms of Progression-free Survival (PFS)	14.2 months Interval 9.9 to 17.6	12.1 months Interval 10.5 to 23.7	11.6 months Interval 8.1 to 12.7

SECONDARY outcome

Timeframe: 26 months

Population: This objective was not completed, as the test was not performed successfully.

The objective is to assess the duration of immunosuppressive cytokine secretion and to identify a receptive interval for active immunotherapy. Immunosuppression will determined by monitoring a panel of immunosuppressive serum/plasma cytokines longitudinally and by determining the response of each patient to Recombivax Hepatitis B (HB) vaccination. Response is defined as seropositive or seronegative to the Hepatitis B surface antigen.

Outcome measures

Outcome measures
Measure	Arm I (ACTIVATE) n=18 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) every 2 weeks starting 4 weeks after the completion of radiation. Subsequent vaccinations were given once a month until clinical or radiographic evidence of progression or death.	Arm II (ACT II STD) n=12 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 200 mg/m2 for the first 5 days of a 28 day cycle.	Arm III (ACT II DI) n=10 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 100 mg/m2 for the first 21 days of a 28 day cycle.
Response to Vaccination	NA Months Standard Deviation NA This objective was not completed, as the test was not performed successfully.	NA Months Standard Deviation NA This objective was not completed, as the test was not performed successfully.	NA Months Standard Deviation NA This objective was not completed, as the test was not performed successfully.

SECONDARY outcome

Timeframe: 26 months

To assess for any potential toxicity to the PEP-3 vaccine immunization in patients with newly diagnosed glioblastoma, Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used to tabulate any toxicities attributable to PEP-3. The number of patients with toxicity attributable to vaccine while on study are tabulated.

Outcome measures

Outcome measures
Measure	Arm I (ACTIVATE) n=18 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) every 2 weeks starting 4 weeks after the completion of radiation. Subsequent vaccinations were given once a month until clinical or radiographic evidence of progression or death.	Arm II (ACT II STD) n=12 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 200 mg/m2 for the first 5 days of a 28 day cycle.	Arm III (ACT II DI) n=10 Participants Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 100 mg/m2 for the first 21 days of a 28 day cycle.
Toxicity to PEP-3 Vaccine Immunization	4 participants	1 participants	7 participants

Adverse Events

Arm I (ACTIVATE)

Serious events: 1 serious events

Other events: 17 other events

Deaths: 0 deaths

Arm II (ACT II STD)

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Arm III (ACT II DI)

Serious events: 3 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Arm I (ACTIVATE) n=18 participants at risk Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) every 2 weeks starting 4 weeks after the completion of radiation. Subsequent vaccinations were given once a month until clinical or radiographic evidence of progression or death.	Arm II (ACT II STD) n=12 participants at risk Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 200 mg/m2 for the first 5 days of a 28 day cycle.	Arm III (ACT II DI) n=10 participants at risk Patients first receive 3 initial vaccinations of an epidermal growth factor receptor variant III (EGRRvIII)- specific peptide (PEP-3) keyhole limpet hemocyanin (KLH) conjugate vaccine and sargramostim (GM-CSF) biweekly starting within 6 weeks of completing radiation. Additional vaccinations were given until clinical or radiographic evidence of progression or death. Patients subsequently receive temozolomide at a targeted dose of 100 mg/m2 for the first 21 days of a 28 day cycle.
Gastrointestinal disorders Dry mouth	0.00% 0/18 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	10.0% 1/10 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
General disorders Non-cardiac chest pain	0.00% 0/18 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	10.0% 1/10 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Immune system disorders Allergic reaction	5.6% 1/18 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	0.00% 0/10 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/18 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	20.0% 2/10 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Skin and subcutaneous tissue disorders Rash acneiform	0.00% 0/18 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	10.0% 1/10 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Skin and subcutaneous tissue disorders Rash maculo-papular	0.00% 0/18 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	20.0% 2/10 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Vascular disorders Flushing	0.00% 0/18 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	30.0% 3/10 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.
Vascular disorders Hypotension	0.00% 0/18 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	0.00% 0/12 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.	10.0% 1/10 • 26 months The adverse events were gathered in Common Terminology Criteria for Adverse Events v.3.0, and have been converted to v.4.0 for entry into ClinicalTrials.gov.

Other adverse events

Additional Information

Dr. John H. Sampson

Duke University Medical Center

Phone: 919-684-9041

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place