Trial Outcomes & Findings for Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas (NCT NCT03334305)

Last Updated: 2026-04-23

Results Overview

Percentage of subjects with grade 3 or greater adverse events. Adverse events (AEs) were summarized in the safety population (N = 5) at the participant level. For each AE term, a participant was counted once using the maximum observed CTCAE grade. Recurrent occurrences of the same AE in a participant were not counted multiple times.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death, whichever occurs first, up to 10 months

Results posted on

2026-04-23

Participant Flow

From 08/27/2018 (first enrollment date) to 03/10/2023 (last enrollment date), 18 patients were accrued to Arm A. Arm B never enrolled participants - study was terminated. Enrollment date is date of consent. Of these, 13 patients were not eligible. Five patients were eligible and evaluable for efficacy and toxicity analyses.

Twelve participants were ineligible due to histology and one was withdrawn at direction of physician.

Participant milestones

Participant milestones
Measure	Group A Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) TTRNA-DC vaccines with GM-CSF: After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. Dose-intensified TMZ: After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. TTRNA-xALT: During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. Td vaccine: A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Group B Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with embedded GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines are given intradermal. After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. A full Td booster will be administered IM at Vaccine #1 and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.
Overall Study STARTED	5	0
Overall Study COMPLETED	1	0
Overall Study NOT COMPLETED	4	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) TTRNA-DC vaccines with GM-CSF: After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. Dose-intensified TMZ: After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. TTRNA-xALT: During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. Td vaccine: A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Group B Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with embedded GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines are given intradermal. After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. A full Td booster will be administered IM at Vaccine #1 and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.
Overall Study Withdrawal by Subject	1	0
Overall Study Adverse Event	1	0
Overall Study Disease Progression	2	0

Baseline Characteristics

Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A n=5 Participants Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) TTRNA-DC vaccines with GM-CSF: After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. Dose-intensified TMZ: After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. TTRNA-xALT: During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. Td vaccine: A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Group B Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with embedded GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines are given intradermal. After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. A full Td booster will be administered IM at Vaccine #1 and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Total n=5 Participants Total of all reporting groups
Age, Continuous	17 years n=60 Participants	—	17 years n=116 Participants
Sex: Female, Male Female	1 Participants n=60 Participants	0 Participants n=56 Participants	1 Participants n=116 Participants
Sex: Female, Male Male	4 Participants n=60 Participants	0 Participants n=56 Participants	4 Participants n=116 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants
Race (NIH/OMB) Asian	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants
Race (NIH/OMB) Black or African American	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants
Race (NIH/OMB) White	5 Participants n=60 Participants	0 Participants n=56 Participants	5 Participants n=116 Participants
Race (NIH/OMB) More than one race	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=60 Participants	0 Participants n=56 Participants	0 Participants n=116 Participants
Region of Enrollment United States	5 participants n=60 Participants	—	5 participants n=116 Participants

PRIMARY outcome

Timeframe: From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death, whichever occurs first, up to 10 months

Population: The study was terminated prior to commencement in Arm B. Single-arm analysis; no comparison group.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) TTRNA-DC vaccines with GM-CSF: After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. Dose-intensified TMZ: After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. TTRNA-xALT: During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. Td vaccine: A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Group B Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with embedded GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines are given intradermal. After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. A full Td booster will be administered IM at Vaccine #1 and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.
Evaluate Safety of TTRNA-DCs and TTRNA-xALT	1 Participants	—

SECONDARY outcome

Timeframe: Up to 10 months

Population: The trial was terminated prior to commencement in Arm B. Single-arm analysis; no comparison group.

Number of subjects completing treatment. Completion defined as receipt of ≥3 DC vaccinations.

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) TTRNA-DC vaccines with GM-CSF: After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. Dose-intensified TMZ: After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. TTRNA-xALT: During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. Td vaccine: A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Group B Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with embedded GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines are given intradermal. After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. A full Td booster will be administered IM at Vaccine #1 and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.
Determine Feasibility of Completing Treatment	4 participants	—

SECONDARY outcome

Timeframe: baseline to up to 10 months after initiation of treatment

Population: Group A Single-arm analysis; no comparison group.

Change in CD4:CD8 T-cell ratio from baseline to post-treatment immune assessment measured in peripheral blood samples.

Outcome measures

Outcome measures
Measure	Group A n=4 Participants Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) TTRNA-DC vaccines with GM-CSF: After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. Dose-intensified TMZ: After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. TTRNA-xALT: During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. Td vaccine: A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Group B Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with embedded GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines are given intradermal. After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. A full Td booster will be administered IM at Vaccine #1 and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.
Change in CD4:CD8 T-cell Ratio	-0.67 Change in CD4:CD8 ratio Standard Deviation 0.29	—

SECONDARY outcome

Timeframe: From date of first treatment until documented disease progression or death, assessed during study follow-up (up to approximately 3 years)

Population: The trial was terminated prior to commencement in Arm B. Single-arm analysis; no comparison group.

Median time to progression

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) TTRNA-DC vaccines with GM-CSF: After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. Dose-intensified TMZ: After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. TTRNA-xALT: During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. Td vaccine: A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Group B Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with embedded GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines are given intradermal. After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. A full Td booster will be administered IM at Vaccine #1 and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.
Progression-free Survival (PFS)	314 days Interval 10.0 to 697.0	—

SECONDARY outcome

Timeframe: From date of first treatment until death from any cause, assessed during study follow-up (up to approximately 3 years)

Population: The trial was terminated prior to the commencement of Arm B. Single-arm analysis; no comparison group.

Median time to death

Outcome measures

Outcome measures
Measure	Group A n=5 Participants Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) TTRNA-DC vaccines with GM-CSF: After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. Dose-intensified TMZ: After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. TTRNA-xALT: During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. Td vaccine: A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Group B Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with embedded GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines are given intradermal. After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. A full Td booster will be administered IM at Vaccine #1 and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.
Overall Survival (OS)	913 days Interval 471.0 to 991.0	—

Adverse Events

Group A

Serious events: 1 serious events

Other events: 1 other events

Deaths: 3 deaths

Group B

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group A n=5 participants at risk Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) TTRNA-DC vaccines with GM-CSF: After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. Dose-intensified TMZ: After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. TTRNA-xALT: During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. Td vaccine: A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Group B Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with embedded GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines are given intradermal. After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. A full Td booster will be administered IM at Vaccine #1 and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.
General disorders Muscle weakness	20.0% 1/5 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
Nervous system disorders Dysphasia	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
Nervous system disorders Ischemia cerebrovascular	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
Nervous system disorders Stroke	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.

Other adverse events

Other adverse events
Measure	Group A n=5 participants at risk Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs) TTRNA-DC vaccines with GM-CSF: After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines will be embedded with GM-CSF (150 µg per injection) and given intradermal. Dose-intensified TMZ: After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. TTRNA-xALT: During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. Td vaccine: A full Td booster vaccine will be administered IM at Vaccine #1 to all subjects, and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.	Group B Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs) After chemoradiation subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with embedded GM-CSF. Monthly DC vaccines will be given during TMZ Cycles 2-5 for Groups A and B and 48-96 hours after completion of TMZ Cycle 6 Day 21 for Group A and 12-36 hours after HSCs for Group B. All subjects will receive an additional two bi-weekly vaccines during Cycle 6 for a total of 10 DC vaccines. All DC vaccines are given intradermal. After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations. Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of \> 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion. During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects. A full Td booster will be administered IM at Vaccine #1 and vaccine site pretreatment will be administered to all subjects prior to Vaccine#3, #6, and #8.
General disorders Fatigue	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
Ear and labyrinth disorders Vestibular disorder	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
General disorders Hypersomnia	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
Blood and lymphatic system disorders CD4 lymphocytes decreased	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
Blood and lymphatic system disorders Lymphocyte count decreased	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
Investigations Hypocalemia	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
Investigations Hypokalemia	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
Skin and subcutaneous tissue disorders Rash maculo-papular	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.
Skin and subcutaneous tissue disorders Urticaria	20.0% 1/5 • Number of events 1 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.	— 0/0 • From start of leukapheresis to 24 hours after completion of procedure and from first administration of DC vaccine through 30 days after the last dose of trial drug or death, whichever occurs first (up to approximately 3 years) Adverse events were collected for participants enrolled in Arm A. Arm B did not enroll participants because the study was terminated early. Serious and non-serious adverse events were summarized descriptively.

Additional Information

Duane Mitchell, MD, PhD

University of Florida

Phone: 352-273-9000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place