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| ID | Type | Description | Link |
|---|---|---|---|
| 2R42CA153845-02 | U.S. NIH Grant/Contract | View source |
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Funding
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| Name | Class |
|---|---|
| Annias Immunotherapeutics, Inc. | OTHER |
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) | NIH |
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Newly diagnosed glioblastoma (GBM) patients with complete or partial surgical resection who were CMV seropositive patients were eligible to enroll on this trial. Patients were enrolled following standard of care chemoradiation and prior to initiation of post-radiation cycles of temozolomide (TMZ) provided they met all eligibility criteria. All eligible patients received a tetanus-diphtheria (Td) vaccination. Patients enrolled on study were randomized to receive either standard TMZ or dose-intensified TMZ (excluding the safety cohort who only received standard TMZ). All patients received a pre-conditioning injection of tetanus on day 22 of the first post-radiation cycle of TMZ. The following day, patients received the first of 3 intradermal (i.d.) injections of the study drug cytomegalovirus peptide (PEP-CMV), which contained either a combination of Component A and Component B or Component A only depending upon when they enrolled on study. Vaccines #2 and #3 will be given at 2 week intervals. Patients who were O[6]-methylguanine-DNA methyltransferase (MGMT) unmethylated received one adjuvant cycle of the TMZ regimen according to their assigned TMZ arm. Patients who were MGMT methylated or whose methylation status was inconclusive continue with up to 12 cycles of TMZ. After the completion of a patient's last TMZ cycle, vaccines continued every 4-6 weeks for a maximum number of 20 vaccines (unless tumor progression occurred). The study ended prematurely due to lack of funds. The preliminary results suggest that the vaccine may be capable of generating an immune response.
Patients were enrolled following radiation therapy and prior to initiation of post-radiation therapy cycles of adjuvant TMZ provided they met all eligibility criteria. After signing main consent, patients had immune monitoring blood work collected and received a Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, adsorbed). After meeting all eligibility criteria, patients were randomized to receive either standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28-day cycle) with vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle or to receive dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28-day cycle) with vaccination on day 23 (-1 day, +2 days) of each TMZ cycle (excluding patients enrolled in the safety cohort who only received standard TMZ).
Patients began their initial cycle of adjuvant TMZ as soon as possible following randomization, if applicable. For Arm 1, the adjuvant TMZ cycle(s) will be given as described above. If a patient had an MGMT unmethylated tumor, they discontinued TMZ after the 1st cycle.
All patients received a tetanus pre-conditioning injection in the right groin on day 22 (+1 day) of cycle 1 of adjuvant TMZ. On the following day, patients receive their study vaccine (either a combination of Component A and Component B or Component A only depending upon when they enrolled on study).
Vaccines #2 and #3 were given at 2 week intervals (+ 3 days), which will resulted in a ~35-day delay before starting TMZ cycle 2. MGMT unmethylated patients did not receive subsequent cycles of TMZ, but continued to receive vaccines approximately every 4 (+2) weeks. Originally, patients received the vaccine as follows: 500 µg of PEP-CMV Component A mixed with Montanide Incomplete Freund's Adjuvant (ISA)-51 intradermally administered in the right groin and 2 hours later, 500 µg of PEP-CMV Component B mixed in 150 µg of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) intradermally administered in the left groin. A safety cohort was added in 2017 following hypersensitivity reactions in which patient received different schedules of vaccine Components A and B to determine the source of the hypersensitivity reactions. Following this safety cohort, the randomized study was allowed to reinitiate with changes to vaccine administration procedure.
Subsequent revisions were made to the study in the latter part of 2018, due to a continuation of hypersensitivity reactions, and Component B was removed from the study. Patients then received the vaccine as follows: 500 µg of PEP-CMV Component A mixed with Montanide ISA-51 administered intradermally with half in the right groin and half in the left groin.
Patients were imaged with contrast-enhanced magnetic resonance imaging (MRI) within 2 weeks (+3 days) after vaccine 3 and then approximately every 8 weeks. RANO criteria was used for assessment of pseudo-progression, and patients demonstrating definitive progression were removed from study. Blood for immune monitoring was obtained at several time points.
The study ended prematurely due to lack of funds.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 5-day TMZ: Components A and B | Experimental | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. |
|
| 21-day TMZ: Components A and B | Experimental | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. |
|
| 5-day TMZ: Safety Cohort | Experimental | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Vaccine components A and B were administered separately, with a delay between them, to determine if it was an individual component or a combination of the components that resulted in adverse reactions. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 5-day TMZ | Drug | Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Treatment-related Adverse Events | To assess the safety of PEP-CMV vaccination in combination with adjuvant TMZ, the percentage of patients with unacceptable toxicity will be estimated within each arm. All patients who received any PEP-CMV vaccine will be included in these analyses. | 2 weeks after the 3rd vaccine, which is approximately 12 weeks after consent |
| Immunologic Response as Measured by Peak Number of T Cells That Secrete IFNγ by ELISPOT in Response to Component A of PEP-CMV | The primary analysis will focus on patients who have follow-up immunologic monitoring after the 3rd vaccination with component A alone and before initiation of the second TMZ/vaccine cycle. Such a patient is considered "evaluable" for the immunologic response primary analyses. The Wilcoxon rank sum test will compare treatment groups with regard to the median peak number of T cells that secrete IFNγ by ELISPOT in response to component A of PEP-CMV. Analyses will include only those patients who have an assessment of immune response after receiving 3 vaccinations. | Through study completion, an average of 1.5 years |
| Measure | Description | Time Frame |
|---|---|---|
| Antigen Loss | To determine if tumors are CMV antigen negative by immunohistochemical analysis for the presence of the antigen pp65 at the time of disease progression/recurrence | Through study completion, an average of 1.5 years |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| David Ashley, MBBS, FRACP, PhD | Duke University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Preston Robert Tisch Brain Tumor Center at Duke | Durham | North Carolina | 27710 | United States |
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| Label | URL |
|---|---|
| The Preston Robert Tisch Brain Tumor Center at Duke | View source |
| Duke Cancer Institute | View source |
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PEP-CMV vaccine originally was comprised of Component A (a pp65 synthetic long peptide [SLP]) and Component B (a neutralizing antibody epitope from human CMV glycoprotein B [gB] conjugated to KLH). Component B was removed due to insufficient manufacturing of Component B followed by hypersensitivity reactions in a subset of patients.
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| ID | Title | Description |
|---|---|---|
| FG000 | 5-day TMZ: Components A and B | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered |
| FG001 | 21-day TMZ: Components A and B | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 21-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle) PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered |
| FG002 | 5-day TMZ: Safety Cohort | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Vaccine components A and B were administered separately, with a delay between them, to determine if it was an individual component or a combination of the components that resulted in adverse reactions. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered |
| FG003 | 5-day TMZ: Component A Alone | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ |
| FG004 | 21-day TMZ: Component A Alone | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 21-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle) PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 5-day TMZ: Components A and B | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Treatment-related Adverse Events | To assess the safety of PEP-CMV vaccination in combination with adjuvant TMZ, the percentage of patients with unacceptable toxicity will be estimated within each arm. All patients who received any PEP-CMV vaccine will be included in these analyses. | Posted | Number | percentage of participants | 2 weeks after the 3rd vaccine, which is approximately 12 weeks after consent |
|
24 Months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 5-day TMZ: Components A and B | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sinus tachycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anemia | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Principal Investigator | Duke University Medical Center | (919) 684-5301 | dukebrain1@duke.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan: Study Protocol Document with SAP | Aug 26, 2020 | Jun 15, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D005909 | Glioblastoma |
| ID | Term |
|---|---|
| D001254 | Astrocytoma |
| D005910 | Glioma |
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
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| ID | Term |
|---|---|
| D000077204 | Temozolomide |
| D013745 | Tetanus Toxoid |
| ID | Term |
|---|---|
| D003606 | Dacarbazine |
| D014226 | Triazenes |
| D009930 | Organic Chemicals |
| D007093 | Imidazoles |
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| 5-day TMZ: Component A Alone | Experimental | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. |
|
| 21-day TMZ: Component A Alone | Experimental | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. |
|
|
| 21-day TMZ | Drug | Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle) |
|
|
| PEP-CMV: Component A | Biological | 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered |
|
| Tetanus-Diphtheria booster | Drug | At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) |
|
|
| Tetanus Pre-Conditioning | Drug | All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ |
|
|
| PEP-CMV: Component B | Biological | 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered |
|
| BG001 | 21-day TMZ: Components A and B | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 21-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle) PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered |
| BG002 | 5-day TMZ: Safety Cohort | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Vaccine components A and B were administered separately, with a delay between them, to determine if it was an individual component or a combination of the components that resulted in adverse reactions. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered |
| BG003 | 5-day TMZ: Component A Alone | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ |
| BG004 | 21-day TMZ: Component A Alone | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 21-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle) PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ |
| BG005 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG001 | 21-day TMZ: Components A and B | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 21-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle) PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered |
| OG002 | 5-day TMZ: Safety Cohort | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Vaccine components A and B were administered separately, with a delay between them, to determine if it was an individual component or a combination of the components that resulted in adverse reactions. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered |
| OG003 | 5-day TMZ: Component A Alone | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ |
| OG004 | 21-day TMZ: Component A Alone | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 21-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle) PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ |
|
|
| Primary | Immunologic Response as Measured by Peak Number of T Cells That Secrete IFNγ by ELISPOT in Response to Component A of PEP-CMV | The primary analysis will focus on patients who have follow-up immunologic monitoring after the 3rd vaccination with component A alone and before initiation of the second TMZ/vaccine cycle. Such a patient is considered "evaluable" for the immunologic response primary analyses. The Wilcoxon rank sum test will compare treatment groups with regard to the median peak number of T cells that secrete IFNγ by ELISPOT in response to component A of PEP-CMV. Analyses will include only those patients who have an assessment of immune response after receiving 3 vaccinations. | Participants who received Component A alone as well as an assessment of immune response after receiving 3 vaccinations. Data not collected on Components A and B cohorts or the Safety Cohort. | Posted | Median | Full Range | T cells | Through study completion, an average of 1.5 years |
|
|
|
| Secondary | Antigen Loss | To determine if tumors are CMV antigen negative by immunohistochemical analysis for the presence of the antigen pp65 at the time of disease progression/recurrence | No data collected with respect to this outcome. Tumor was not collected at the time of disease progression/recurrence. | Posted | Through study completion, an average of 1.5 years |
|
|
| 4 |
| 4 |
| 4 |
| 4 |
| 4 |
| 4 |
| EG001 | 21-day TMZ: Components A and B | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 21-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle) PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered | 1 | 1 | 1 | 1 | 1 | 1 |
| EG002 | 5-day TMZ: Safety Cohort | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. Vaccine components A and B were administered separately, with a delay between them, to determine if it was an individual component or a combination of the components that resulted in adverse reactions. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ PEP-CMV: Component B: 500 µg of PEP-CMV Component B (a neutralizing antibody epitope from human CMV glycoprotein B conjugated to Keyhole Limpet Hemocyanin) mixed in 150 µg of GM-CSF intradermally administered | 6 | 6 | 2 | 6 | 6 | 6 |
| EG003 | 5-day TMZ: Component A Alone | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of standard TMZ (150-200 mg/m^2/day on days 1-5 of each 28 day cycle) with PEP-CMV vaccination on Day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 5-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of 150-200 mg/m^2/day on days 1-5 of each 28 day cycle PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ | 8 | 8 | 6 | 8 | 8 | 8 |
| EG004 | 21-day TMZ: Component A Alone | All patients receive Tetanus-Diphtheria booster vaccine at time of enrollment. Cycles of dose-intensified TMZ (75-100 mg/m^2/day on days 1-21 of each 28 day cycle) with PEP-CMV vaccination on day 23 (-1 day, + 2 days) of each TMZ cycle and tetanus pre-conditioning the day before the first vaccine. 21-day TMZ: Chemotherapy agent FDA approved to treat newly-diagnosed glioblastoma given as cycles of dose-intensified TMZ (75-100 mg/m2/day on days 1-21 of each 28 day cycle) PEP-CMV: Component A: 500 µg of PEP-CMV Component A (a synthetic long peptide) mixed with Montanide ISA-51 intradermally administered Tetanus-Diphtheria booster: At time of enrollment, after signing consent and undergoing immune monitoring blood work, patients will receive Tetanus-diphtheria booster vaccination with 0.5 mL of Td (tetanus, diphtheria toxoid, absorbed) Tetanus Pre-Conditioning: All patients will receive a tetanus pre-conditioning injection in the right groin intradermally on day 22 (±1 day) of the first post-radiation cycle of TMZ | 8 | 8 | 4 | 8 | 8 | 8 |
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pancreatitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Chills | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Flu like symptoms | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cytokine release syndrome | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Infections and infestations - Other, Specify: PNEUMONIA | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Investigations - Other, Specify: LACTIC ACIDOSIS | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hydrocephalus | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pyramidal tract syndrome | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Seizure | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Psychosis | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Aspiration | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Blood and lymphatic system disorders - Other, Specify: CUT FACE SHAVING; BLED FOR 2+ HOURS | Blood and lymphatic system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Palpitations | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Ear and labyrinth disorders - Other, Specify: "CLOGGED FEELING" | Ear and labyrinth disorders | CTCAE (4.0) | Systematic Assessment |
|
| Ear pain | Ear and labyrinth disorders | CTCAE (4.0) | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | CTCAE (4.0) | Systematic Assessment |
|
| Conjunctivitis | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Eye disorders - Other, Specify: LEFT EYE WEEPY, RED, SWOLLEN, BLOOD SHOT | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Eye disorders - Other, Specify: RED, ITCHY EYES | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Eye disorders - Other, Specify: REDNESS | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Eye disorders - Other, Specify: REQUIRES BRIGHTER LIGHTS WHEN INSIDE IN ORDER TO SEE | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Photophobia | Eye disorders | CTCAE (4.0) | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dysphagia | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fecal incontinence | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gastrointestinal disorders - Other, Specify: CRAMPING | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hemorrhoids | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Chills | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Edema limbs | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fever | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Flu like symptoms | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gait disturbance | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| General disorders and administration site conditions - Other, Specify: NIGHT SWEATS | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Injection site reaction | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pain | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Allergic reaction | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cytokine release syndrome | Immune system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Enterocolitis infectious | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Infections and infestations - Other, Specify: SHINGLES | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Mucosal infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Skin infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | CTCAE (4.0) | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Blood bilirubin increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Creatinine increased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Lymphocyte count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Neutrophil count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Platelet count decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| White blood cell decreased | Investigations | CTCAE (4.0) | Systematic Assessment |
|
| Anorexia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypercalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyperkalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypernatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypoalbuminemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypocalcemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypoglycemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypokalemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypomagnesemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hyponatremia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypophosphatemia | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Metabolism and nutrition disorders - Other, Specify: NIGHT SWEATS | Metabolism and nutrition disorders | CTCAE (4.0) | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Muscle weakness lower limb | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Neoplasms benign, malignant and unspecified - Other, Specify: SQUAMOUS CELL CARCINOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Systematic Assessment |
|
| Cognitive disturbance | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dysarthria | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dysphasia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Encephalopathy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Lethargy | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Memory impairment | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nervous system disorders - Other, Specify: A LITTLE WOBBLY, OFF BALANCE | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nervous system disorders - Other, Specify: HEMIANOPSIA | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nervous system disorders - Other, Specify: QUADRANTANOPSIA | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Paresthesia | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pyramidal tract syndrome | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Seizure | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Agitation | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Confusion | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Depression | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Restlessness | Psychiatric disorders | CTCAE (4.0) | Systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Urinary frequency | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Urinary incontinence | Renal and urinary disorders | CTCAE (4.0) | Systematic Assessment |
|
| Erectile dysfunction | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
|
| Irregular menstruation | Reproductive system and breast disorders | CTCAE (4.0) | Systematic Assessment |
|
| Allergic rhinitis | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hiccups | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hoarseness | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders - Other, Specify: "LUMP IN THROAT" | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders - Other, Specify: "STRANGE SENSATION ON THROAT" | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Respiratory, thoracic and mediastinal disorders - Other, Specify: DRY THROAT | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Sore throat | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Voice alteration | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other, Specify: DARK CRUSTY SPOTS POSS. ACTINIC KERATOSIS | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment | Top of head |
|
| Skin and subcutaneous tissue disorders - Other, Specify: FEVER BLISTER | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other, Specify: POISON IVY | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Skin and subcutaneous tissue disorders - Other, Specify: POSSIBLE PRECANCEROUS LESION | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Skin induration | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Skin ulceration | Skin and subcutaneous tissue disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hematoma | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hot flashes | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
| Hypotension | Vascular disorders | CTCAE (4.0) | Systematic Assessment |
|
Not provided
Not provided
| D009373 |
| Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D014121 | Toxoids |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |