Immunotherapy Targeted Against Cytomegalovirus in Patient... | NCT03927222

Description Module

Detailed Description

Approximately 64 patients with resected, newly-diagnosed WHO Grade IV glioma who are CMV positive and in which the Methylguanine Methyltransferase (MGMT) is not methylated will be accrued to this study before standard of care radiation therapy (RT) and concurrent TMZ, with the goal of treating 48 patients with dose-intensified temozolomide and pp65 loaded dendritic cell vaccine after completion of standard RT and TMZ.

All enrolled patients will undergo a leukapheresis for the generation of DCs. Patients will then receive approximately 6 weeks of the standard of care radiation therapy (RT) and concurrent TMZ at a standard targeted dose of 75 mg/m2/day. For patients whose initial leukapheresis yields less than 3 vaccines, repeat leukapheresis may be obtained. At the post-RT clinic visit, a single post-RT cycle of dose-intensified TMZ (100 mg/m2/day for 21 days) will be given. On day 23 (± 2 days) of the cycle, patients will receive the first of 3 pp65 DC vaccines. Vaccines #1-3 will be given every two weeks (± 2 days). All patients will receive up to a total of 10 DC vaccines, with vaccines administered every 35 days (± 7 days) after the third vaccine, given bilaterally at the groin site unless progression occurs with no further cycles of TMZ. DC vaccines will be given intradermally (i.d.) and divided equally to both inguinal regions. Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Patients will undergo leukapheresis again for immunologic monitoring with a specific assessment of baseline antigen-specific cellular and humoral immune responses if needed for further DC generations 14 (± 2) days after vaccine #3. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2, the vaccine site will receive a pre-conditioning intradermal injection of Td. Up to 16 patients will receive 111-Indium labeled DCs at the 4th vaccine followed by SPECT/CT imaging immediately, and at 1 and 2 days after injections.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
DC vaccination with Td preconditioning and GM CSF	Experimental	This single-arm phase II study will assess the impact of tetanus pre-conditioning and adjuvant GM-CSF on overall survival of newly diagnosed glioblastoma (GBM) patients who have undergone definitive resection, are unmethylated, and completed standard temozolomide and radiation treatment. All enrolled patients will undergo a leukapheresis for the generation of DCs. Patients will then receive approximately 6 weeks of standard of care radiation therapy (RT) and concurrent TMZ. A single post-RT cycle of dose intensified TMZ (100 mg/m2/day for 21 days) will then be given. On day 23 (± 2 days) of the cycle, patients will receive the first of 3 pp65 DC vaccines every 2 weeks. All patients will receive up to a total of 10 DC vaccines	Biological: Human CMV pp65-LAMP mRNA-pulsed autologous DCs containing GM CSF Drug: Temozolomide Biological: Tetanus-Diphtheria Toxoid (Td) Biological: GM-CSF Biological: 111-Indium-labeling of Cells for in vivo Trafficking Studies

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Human CMV pp65-LAMP mRNA-pulsed autologous DCs containing GM CSF	Biological	2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines.

Measure	Description	Time Frame
Median Overall Survival (OS) of Subjects Receiving Td Pre-conditioning With GM-CSF	Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up has OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.	duration of the study (up to 3 years and 4.5 months)

Measure	Description	Time Frame
Migration and Survival From Vaccine 4	The Cox proportional hazards model will assess the impact of migration on survival after vaccine #4. Migration is defined as the maximum percentage of 111In-labeled dendritic cells (DCs) reaching inguinal nodes during the 48 hours after the 4th vaccination. The hazard ratio associated with a 1-unit change in migration will be estimated with 95% confidence intervals.CSF to site-draining inguinal lymph nodes after Td pre-conditioning and survival after vaccine # 4.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥ 18 years
Newly diagnosed World Health Organization (WHO) Grade IV Glioma with definitive resection prior to the consent, with a residual radiographic contrast enhancing disease on the postoperative computed tomography (CT) or Magnetic Resonance Imaging (MRI) of <1 cm in maximal diameter in any plane.
Able to receive standard of care radiation and chemotherapy for approximately 6 weeks duration and of more than 54 Gray (GY)
MRI post radiation therapy (RT) does not show progressive disease outside the radiation field
Enough tumor tissue available for determination of methylguanine-DNA methyltransferase (MGMT) gene promoter status (must be unmethylated) or prior pathology report available confirming MGMT gene promoter status
Cytomegalovirus (CMV) Seropositive
Karnofsky Performance Status (KPS) of ≥ 70%
Hemoglobin ≥ 9.0 g/dl, absolute neutrophil count (ANC) ≥ 1,000 cells/µl, platelets ≥ 100,000 cells/µl prior to starting TMZ cycle 1 (patient must meet these criteria within 4 weeks after the end of XRT/TMZ to be eligible)
Serum creatinine ≤ 3 times institutional upper limit of normal (ULN) for age, aspartate aminotransferase (AST) ≤ 3 times institutional upper limit of normal for age
Bilirubin ≤ 1.5 times upper limit of normal prior to starting TMZ cycle 1 (Exception: Patient has known Gilbert's Syndrome or patient has suspected Gilbert's Syndrome, for which additional lab testing of direct and/or indirect bilirubin supports this diagnosis. In these instances, a total bilirubin of ≤ 3.0 x ULN is acceptable.)
Signed informed consent approved by the Institutional Review Board
Female patients must not be pregnant or breastfeeding. Female patients of childbearing potential (defined as < 2 years after last menstruation or not surgically sterile) must use a highly effective contraceptive method (allowed methods of birth control, [i.e. with a failure rate of < 1% per year] are implants, injectables, combined oral contraceptives, intrauterine device [IUD; only hormonal], sexual abstinence or vasectomized partner) during the trial and for a period of > 6 months following the last administration of trial drug(s). Female patients with an intact uterus (unless amenorrhea for the last 24 months) must have a negative serum pregnancy test within 48 hours prior to first study procedure (leukapheresis).
Fertile male patients must agree to use a highly effective contraceptive method (allowed methods of birth control [i.e. with a failure rate of < 1% per year] include a female partner using implants, injectables, combined oral contraceptives, intrauterine devices (IUDs) [only hormonal], sexual abstinence or prior vasectomy) during the trial and for a period of > 6 months following the last administration of trial drugs.

Exclusion Criteria:

Pregnant or breastfeeding.
Women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception.
Patients with known potentially anaphylactic allergic reactions to gadolinium- diethylenetriamine penta-acetic acid (DTPA).
Patients who cannot undergo MRI or SPECT due to obesity or to having certain metal in their bodies (specifically pacemakers, infusion pumps, metal aneurysm clips, metal prostheses, joints, rods, or plates).
Patients with evidence of tumor in the brainstem, cerebellum, or spinal cord, radiological evidence of multifocal disease, or leptomeningeal disease.
Severe, active comorbidity, including any of the following:
1. Unstable angina and/or congestive heart failure requiring hospitalization;
2. Transmural myocardial infarction within the last 6 months;
3. Acute bacterial or fungal infection requiring intravenous antibiotics at the time of study initiation;
4. Chronic obstructive pulmonary disease exacerbation or other respiratory illness r requiring hospitalization or precluding study therapy;
5. Known hepatic insufficiency resulting in clinical jaundice and/or coagulation defects;
6. Known Human Immunodeficiency Virus (HIV) and Hepatitis C positive status;
7. Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy;
8. Active connective tissue disorders, such as lupus or scleroderma that, in the opinion of the treating physician, may put the patient at high risk for radiation toxicity.
Co-medication that may interfere with study results; e.g. immuno-suppressive agents other than corticosteroids
Prior, unrelated malignancy requiring current active treatment with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin. (Treatment with tamoxifen or aromatase inhibitors or other hormonal therapy that may be indicated in the prevention of prior cancer disease recurrence, are not considered current active treatment.)
Patients are not permitted to have had any other conventional therapeutic intervention other than steroids prior to enrollment outside of the standard of care chemotherapy and radiation therapy. Patients who receive previous inguinal lymph node dissection, radiosurgery, brachytherapy, or radiolabeled monoclonal antibodies will be excluded
Current, recent (within 4 weeks of the administration of this study agent), or planned participation in an experimental drug study.
Known history of autoimmune disease (with the exceptions of medically-controlled hypothyroidism and Type I Diabetes Mellitus).

Name	Affiliation	Role
Mustafa Khasraw, MBChB, MD, FRCP, FRACP	Duke University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Duke University Medical Center		Durham	North Carolina	27710	United States

Label	URL
The Preston Robert Tisch Brain Tumor Center at Duke	View source
Duke Cancer Institute	View source
Duke Health

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	DC Vaccination With Td Preconditioning and GM CSF	Human CMV pp65-LAMP mRNA-pulsed autologous DCs containing GM CSF: 2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines. Temozolomide: Temozolomide is a chemotherapy drug given to all enrolled patients at the post-RT clinic visit as dose-intensified TMZ (100 mg/m2/day for 21 days). Tetanus-Diphtheria Toxoid (Td): Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2 the vaccine site will receive a pre-conditioning intradermal injection of Td (1 flocculation unit (Lf), in 0.3 mL of saline for a total of 0.4 mL). GM-CSF: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a sterile, white, preservative-free lyophilized powder in a vial containing 250 mcg that will be reconstituted in 0.5 mL of sterile water for injection and used as an adjuvant with the DC vaccine. 111-Indium-labeling of Cells for in vivo Trafficking Studies: 111-In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs labeled with 111-In (50 μCi / 5 x 10^7 DCs) and given i.d. as the fourth vaccine. In up to 16 patients, the fourth vaccine will be labeled with 111-In (50 μCi / 5 x 10^7 DCs) prior to injection.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

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	Feb 4, 2022

Arm/Group Information

ID	Title	Description
BG000	DC Vaccination With Td Preconditioning and GM CSF	Human CMV pp65-LAMP mRNA-pulsed autologous DCs containing GM CSF: 2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines. Temozolomide: Temozolomide is a chemotherapy drug given to all enrolled patients at the post-RT clinic visit as dose-intensified TMZ (100 mg/m2/day for 21 days). Tetanus-Diphtheria Toxoid (Td): Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2 the vaccine site will receive a pre-conditioning intradermal injection of Td (1 flocculation unit (Lf), in 0.3 mL of saline for a total of 0.4 mL). GM-CSF: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a sterile, white, preservative-free lyophilized powder in a vial containing 250 mcg that will be reconstituted in 0.5 mL of sterile water for injection and used as an adjuvant with the DC vaccine. 111-Indium-labeling of Cells for in vivo Trafficking Studies: 111-In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs labeled with 111-In (50 μCi / 5 x 10^7 DCs) and given i.d. as the fourth vaccine. In up to 16 patients, the fourth vaccine will be labeled with 111-In (50 μCi / 5 x 10^7 DCs) prior to injection.

Units	Counts
Participants	BG0006

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

Median Overall Survival (OS) of Subjects Receiving Td Pre-conditioning With GM-CSF

Time in months from the start of study treatment to date of death due to any cause. Patients alive as of the last follow-up has OS censored at the last follow-up date. Median OS was estimated using a Kaplan-Meier curve.

Posted

Median

95% Confidence Interval

months

duration of the study (up to 3 years and 4.5 months)

ID	Title	Description
OG000	DC Vaccination With Td Preconditioning and GM CSF	Human CMV pp65-LAMP mRNA-pulsed autologous DCs containing GM CSF: 2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines. Temozolomide: Temozolomide is a chemotherapy drug given to all enrolled patients at the post-RT clinic visit as dose-intensified TMZ (100 mg/m2/day for 21 days). Tetanus-Diphtheria Toxoid (Td): Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2 the vaccine site will receive a pre-conditioning intradermal injection of Td (1 flocculation unit (Lf), in 0.3 mL of saline for a total of 0.4 mL). GM-CSF: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a sterile, white, preservative-free lyophilized powder in a vial containing 250 mcg that will be reconstituted in 0.5 mL of sterile water for injection and used as an adjuvant with the DC vaccine. 111-Indium-labeling of Cells for in vivo Trafficking Studies: 111-In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs labeled with 111-In (50 μCi / 5 x 10^7 DCs) and given i.d. as the fourth vaccine. In up to 16 patients, the fourth vaccine will be labeled with 111-In (50 μCi / 5 x 10^7 DCs) prior to injection.

Units	Counts
Participants	OG0006

Title

Denominators

Categories

Title	Measurements
	OG00017.4(13.3 to NA)No not enough failure times to estimate the upper bound.

Secondary

Migration and Survival From Vaccine 4

The Cox proportional hazards model will assess the impact of migration on survival after vaccine #4. Migration is defined as the maximum percentage of 111In-labeled dendritic cells (DCs) reaching inguinal nodes during the 48 hours after the 4th vaccination. The hazard ratio associated with a 1-unit change in migration will be estimated with 95% confidence intervals.CSF to site-draining inguinal lymph nodes after Td pre-conditioning and survival after vaccine # 4.

Data not collected.

Posted

5 years

ID	Title	Description
OG000	DC Vaccination With Td Preconditioning and GM CSF	Human CMV pp65-LAMP mRNA-pulsed autologous DCs (dendritic cells) containing GM CSF: 2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines. Temozolomide: Temozolomide is a chemotherapy drug given to all enrolled patients at the post-RT clinic visit as dose-intensified TMZ (100 mg/m2/day for 21 days). Tetanus-Diphtheria Toxoid (Td): Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2 the vaccine site will receive a pre-conditioning intradermal injection of Td (1 flocculation unit (Lf), in 0.3 mL of saline for a total of 0.4 mL). GM-CSF: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a sterile, white, preservative-free lyophilized powder in a vial containing 250 mcg that will be reconstituted in 0.5 mL of sterile water for injection and used as an adjuvant with the DC vaccine. 111-Indium-labeling of Cells for in vivo Trafficking Studies: 111-In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs labeled with 111-In (50 μCi / 5 x 10^7 DCs) and given i.d. as the fourth vaccine. In up to 16 patients, the fourth vaccine will be labeled with 111-In (50 μCi / 5 x 10^7 DCs) prior to injection.

Secondary

Chemokine (C-C Motif) Ligand 3 (CCL3) and Survival From Vaccine 4

The Cox proportional hazards model will assess the impact of CCL3 on survival post-vaccine 4. The hazard ratio associate with a 1-unit increase in CCL3 will be estimated with 95% confidence intervals

Data not collected.

Posted

5 years

ID	Title	Description
OG000	DC Vaccination With Td Preconditioning and GM CSF	Human CMV pp65-LAMP mRNA-pulsed autologous DCs (dendritic cells) containing GM CSF: 2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines. Temozolomide: Temozolomide is a chemotherapy drug given to all enrolled patients at the post-RT clinic visit as dose-intensified TMZ (100 mg/m2/day for 21 days). Tetanus-Diphtheria Toxoid (Td): Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2 the vaccine site will receive a pre-conditioning intradermal injection of Td (1 flocculation unit (Lf), in 0.3 mL of saline for a total of 0.4 mL). GM-CSF: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a sterile, white, preservative-free lyophilized powder in a vial containing 250 mcg that will be reconstituted in 0.5 mL of sterile water for injection and used as an adjuvant with the DC vaccine. 111-Indium-labeling of Cells for in vivo Trafficking Studies: 111-In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs labeled with 111-In (50 μCi / 5 x 10^7 DCs) and given i.d. as the fourth vaccine. In up to 16 patients, the fourth vaccine will be labeled with 111-In (50 μCi / 5 x 10^7 DCs) prior to injection.

Secondary

Polyfunctionality and Survival From Vaccine 4

Cox proportional hazards model will assess the association between fold change increase between baseline and the leukapheresis 2 in the frequency of pp65 antigen-specific CD8+ T cells producing three or more cytokines (IFNγ, CCL3, IL-2, TNFα, CD107a), and survival post-vaccine 4. The hazard ratio associate with a 1-unit fold change in polyfunctionality will be estimated with 95% confidence intervals.

Data not collected.

Posted

5 years

ID	Title	Description
OG000	DC Vaccination With Td Preconditioning and GM CSF	Human CMV pp65-LAMP mRNA-pulsed autologous DCs (dendritic cells) containing GM CSF: 2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines. Temozolomide: Temozolomide is a chemotherapy drug given to all enrolled patients at the post-RT clinic visit as dose-intensified TMZ (100 mg/m2/day for 21 days). Tetanus-Diphtheria Toxoid (Td): Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2 the vaccine site will receive a pre-conditioning intradermal injection of Td (1 flocculation unit (Lf), in 0.3 mL of saline for a total of 0.4 mL). GM-CSF: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a sterile, white, preservative-free lyophilized powder in a vial containing 250 mcg that will be reconstituted in 0.5 mL of sterile water for injection and used as an adjuvant with the DC vaccine. 111-Indium-labeling of Cells for in vivo Trafficking Studies: 111-In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs labeled with 111-In (50 μCi / 5 x 10^7 DCs) and given i.d. as the fourth vaccine. In up to 16 patients, the fourth vaccine will be labeled with 111-In (50 μCi / 5 x 10^7 DCs) prior to injection.

Secondary

Maximum Peak Increase From Vaccine 1 in Percent Regulatory T Cells (TReg) of CD4+ T Cells

The mean difference in TRegs between vaccine 1 and the maximum measured level post-vaccine 1 will be reported.

Data not collected.

Posted

1 year

ID	Title	Description
OG000	DC Vaccination With Td Preconditioning and GM CSF	Human CMV pp65-LAMP mRNA-pulsed autologous DCs (dendritic cells) containing GM CSF: 2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines. Temozolomide: Temozolomide is a chemotherapy drug given to all enrolled patients at the post-RT clinic visit as dose-intensified TMZ (100 mg/m2/day for 21 days). Tetanus-Diphtheria Toxoid (Td): Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2 the vaccine site will receive a pre-conditioning intradermal injection of Td (1 flocculation unit (Lf), in 0.3 mL of saline for a total of 0.4 mL). GM-CSF: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a sterile, white, preservative-free lyophilized powder in a vial containing 250 mcg that will be reconstituted in 0.5 mL of sterile water for injection and used as an adjuvant with the DC vaccine. 111-Indium-labeling of Cells for in vivo Trafficking Studies: 111-In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs labeled with 111-In (50 μCi / 5 x 10^7 DCs) and given i.d. as the fourth vaccine. In up to 16 patients, the fourth vaccine will be labeled with 111-In (50 μCi / 5 x 10^7 DCs) prior to injection.

Secondary

Number of Participants With Unacceptable Toxicity

An unacceptable toxicity is defined as any grade 3 or greater toxicity that is possibly, probably, or definitely attributed to the pre-conditioning agent Td or pp65 DC vaccine that does not resolve to baseline within 3 weeks; any Grade 3 hypersensitivity reactions or autoimmune toxicity requiring steroids or hormone replacement; , and is not due to progressive disease, or any life-threatening event not attributable to concomitant medication, co-morbid event, or disease progression. Toxicities will be graded according to the National Cancer Institute Common Toxicity Criteria of Adverse Events (NCI CTCAE) version 5 criteria.

Posted

Count of Participants

Participants

1 year

ID	Title	Description
OG000	DC Vaccination With Td Preconditioning and GM CSF	Human CMV pp65-LAMP mRNA-pulsed autologous DCs (dendritic cells) containing GM CSF: 2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines. Temozolomide: Temozolomide is a chemotherapy drug given to all enrolled patients at the post-RT clinic visit as dose-intensified TMZ (100 mg/m2/day for 21 days). Tetanus-Diphtheria Toxoid (Td): Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2 the vaccine site will receive a pre-conditioning intradermal injection of Td (1 flocculation unit (Lf), in 0.3 mL of saline for a total of 0.4 mL). GM-CSF: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a sterile, white, preservative-free lyophilized powder in a vial containing 250 mcg that will be reconstituted in 0.5 mL of sterile water for injection and used as an adjuvant with the DC vaccine. 111-Indium-labeling of Cells for in vivo Trafficking Studies: 111-In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs labeled with 111-In (50 μCi / 5 x 10^7 DCs) and given i.d. as the fourth vaccine. In up to 16 patients, the fourth vaccine will be labeled with 111-In (50 μCi / 5 x 10^7 DCs) prior to injection.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	DC Vaccination With Td Preconditioning and GM CSF	Human CMV pp65-LAMP mRNA-pulsed autologous DCs (dendritic cells) containing GM CSF: 2x10^7 human CMV pp65-LAMP mRNA-pulsed autologous DCs are given intradermally and bilaterally at the groin site (divided equally to both inguinal regions). Patients will receive up to a total of 10 DC vaccines. Temozolomide: Temozolomide is a chemotherapy drug given to all enrolled patients at the post-RT clinic visit as dose-intensified TMZ (100 mg/m2/day for 21 days). Tetanus-Diphtheria Toxoid (Td): Before the first DC vaccination, patients will receive 0.5 mL of Td (tetanus and diphtheria toxoids adsorbed) intramuscularly into the deltoid muscle to ensure adequate immunity to the tetanus antigen. Prior to pp65 DC vaccination #4,(3±1) weeks after leukapheresis 2 the vaccine site will receive a pre-conditioning intradermal injection of Td (1 flocculation unit (Lf), in 0.3 mL of saline for a total of 0.4 mL). GM-CSF: Granulocyte macrophage-colony stimulating factor (GM-CSF) is a sterile, white, preservative-free lyophilized powder in a vial containing 250 mcg that will be reconstituted in 0.5 mL of sterile water for injection and used as an adjuvant with the DC vaccine. 111-Indium-labeling of Cells for in vivo Trafficking Studies: 111-In-labeled DCs are 2 x 10^7 pp65-LAMP mRNA loaded mature DCs labeled with 111-In (50 μCi / 5 x 10^7 DCs) and given i.d. as the fourth vaccine. In up to 16 patients, the fourth vaccine will be labeled with 111-In (50 μCi / 5 x 10^7 DCs) prior to injection.	5	6	0	6	6	6

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Agitation	Psychiatric disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Alanine aminotransferase increased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Allergic reaction	Immune system disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Anemia	Blood and lymphatic system disorders	CTCAE (5.0)	Systematic Assessment	EG0004 affected6 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment	EG0004 affected6 at risk
Anxiety	Psychiatric disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Atrial fibrillation	Cardiac disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Back pain	Musculoskeletal and connective tissue disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Blood bilirubin increased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Blurred vision	Eye disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Cholesterol high	Investigations	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Constipation	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Creatinine increased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Depression	Psychiatric disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Dizziness	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Dry skin	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Dysesthesia	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Dysphasia	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Ear pain	Ear and labyrinth disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Eye disorders - Other, specify	Eye disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Fatigue	General disorders	CTCAE (5.0)	Systematic Assessment	EG0005 affected6 at risk
Flatulence	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0005 affected6 at risk
General disorders and administration site conditions - Other, specify	General disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Headache	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0004 affected6 at risk
Hearing impaired	Ear and labyrinth disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Hemorrhoids	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Hypertension	Vascular disorders	CTCAE (5.0)	Systematic Assessment	EG0005 affected6 at risk
Hypocalcemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Hypotension	Vascular disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Infections and infestations - Other, specify	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Injection site reaction	General disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Injury, poisoning and procedural complications - Other, specify	Injury, poisoning and procedural complications	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Insomnia	Psychiatric disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Investigations - Other, specify	Investigations	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Lymphocyte count decreased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0004 affected6 at risk
Memory impairment	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Nausea	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0005 affected6 at risk
Nervous system disorders - Other, specify	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Neutrophil count decreased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Platelet count decreased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0003 affected6 at risk
Pruritus	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
Respiratory, thoracic and mediastinal disorders - Other, specify	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Seizure	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Tinnitus	Ear and labyrinth disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk
Urinary tract infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0002 affected6 at risk
White blood cell decreased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0001 affected6 at risk

ID	Term
D001254	Astrocytoma
D005910	Glioma
D018302	Neoplasms, Neuroepithelial
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009375	Neoplasms, Glandular and Epithelial
D009380	Neoplasms, Nerve Tissue
D003015	Clostridium Infections
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections

ID	Term
D000077204	Temozolomide
D016178	Granulocyte-Macrophage Colony-Stimulating Factor
C081222	sargramostim

ID	Term
D003606	Dacarbazine
D014226	Triazenes
D009930	Organic Chemicals
D007093	Imidazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D003115	Colony-Stimulating Factors
D006023	Glycoproteins
D006001	Glycoconjugates
D002241	Carbohydrates
D016298	Hematopoietic Cell Growth Factors
D016207	Cytokines
D036341	Intercellular Signaling Peptides and Proteins
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D011506	Proteins
D001685	Biological Factors