Trial Outcomes & Findings for Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma (NCT NCT03927222)
NCT ID: NCT03927222
Last Updated: 2024-04-08
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
6 participants
Primary outcome timeframe
duration of the study (up to 3 years and 4.5 months)
Results posted on
2024-04-08
Participant Flow
Participant milestones
| Measure |
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.
|
|---|---|
|
Overall Study
STARTED
|
6
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
6
|
Reasons for withdrawal
| Measure |
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.
|
|---|---|
|
Overall Study
Progression
|
3
|
|
Overall Study
CMV testing results inconclusive
|
1
|
|
Overall Study
Unable to generate enough vaccines
|
1
|
|
Overall Study
Early study termination
|
1
|
Baseline Characteristics
Immunotherapy Targeted Against Cytomegalovirus in Patients With Newly-Diagnosed WHO Grade IV Unmethylated Glioma
Baseline characteristics by cohort
| Measure |
DC Vaccination With Td Preconditioning and GM CSF
n=6 Participants
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.
|
|---|---|
|
Age, Continuous
|
63 years
STANDARD_DEVIATION 12.2 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: duration of the study (up to 3 years and 4.5 months)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.
Outcome measures
| Measure |
DC Vaccination With Td Preconditioning and GM CSF
n=6 Participants
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.
|
|---|---|
|
Median Overall Survival (OS) of Subjects Receiving Td Pre-conditioning With GM-CSF
|
17.4 months
Interval 13.3 to
No not enough failure times to estimate the upper bound.
|
SECONDARY outcome
Timeframe: 5 yearsPopulation: Data not collected.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 5 yearsPopulation: Data not collected.
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
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 5 yearsPopulation: Data not collected.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 1 yearPopulation: Data not collected.
The mean difference in TRegs between vaccine 1 and the maximum measured level post-vaccine 1 will be reported.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 1 yearAn 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.
Outcome measures
| Measure |
DC Vaccination With Td Preconditioning and GM CSF
n=6 Participants
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.
|
|---|---|
|
Number of Participants With Unacceptable Toxicity
|
0 Participants
|
Adverse Events
DC Vaccination With Td Preconditioning and GM CSF
Serious events: 0 serious events
Other events: 6 other events
Deaths: 5 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
DC Vaccination With Td Preconditioning and GM CSF
n=6 participants at risk
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.
|
|---|---|
|
Psychiatric disorders
Agitation
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Investigations
Alanine aminotransferase increased
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Immune system disorders
Allergic reaction
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Blood and lymphatic system disorders
Anemia
|
66.7%
4/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Metabolism and nutrition disorders
Anorexia
|
66.7%
4/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Psychiatric disorders
Anxiety
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Cardiac disorders
Atrial fibrillation
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Investigations
Blood bilirubin increased
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Eye disorders
Blurred vision
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Investigations
Cholesterol high
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Investigations
Creatinine increased
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Psychiatric disorders
Depression
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Nervous system disorders
Dizziness
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Nervous system disorders
Dysesthesia
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Nervous system disorders
Dysphasia
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Ear and labyrinth disorders
Ear pain
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Eye disorders
Eye disorders - Other, specify
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
General disorders
Fatigue
|
83.3%
5/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Gastrointestinal disorders
Flatulence
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
83.3%
5/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
General disorders
General disorders and administration site conditions - Other, specify
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Nervous system disorders
Headache
|
66.7%
4/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Ear and labyrinth disorders
Hearing impaired
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Gastrointestinal disorders
Hemorrhoids
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Vascular disorders
Hypertension
|
83.3%
5/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Metabolism and nutrition disorders
Hypokalemia
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Vascular disorders
Hypotension
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Infections and infestations
Infections and infestations - Other, specify
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
General disorders
Injection site reaction
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Injury, poisoning and procedural complications
Injury, poisoning and procedural complications - Other, specify
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Psychiatric disorders
Insomnia
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Investigations
Investigations - Other, specify
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Investigations
Lymphocyte count decreased
|
66.7%
4/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Nervous system disorders
Memory impairment
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Gastrointestinal disorders
Nausea
|
83.3%
5/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Nervous system disorders
Nervous system disorders - Other, specify
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Investigations
Neutrophil count decreased
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Investigations
Platelet count decreased
|
50.0%
3/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory, thoracic and mediastinal disorders - Other, specify
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Nervous system disorders
Seizure
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other, specify
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Ear and labyrinth disorders
Tinnitus
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Infections and infestations
Urinary tract infection
|
33.3%
2/6 • Duration of the study (up to 3 years and 4.5 months)
|
|
Investigations
White blood cell decreased
|
16.7%
1/6 • Duration of the study (up to 3 years and 4.5 months)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place