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ACTIVE NOT RECRUITING
NCT03688178
PHASE2

DC Migration Study to Evaluate TReg Depletion In GBM Patients With and Without Varlilumab

Sponsor: Annick Desjardins, MD

View on ClinicalTrials.gov

Summary

Patients with newly diagnosed glioblastoma will be consented following tumor resection then undergo leukapheresis for harvest of peripheral blood leukocytes for generation of dendritic cells. Subjects will then receive standard of care (planned 6 weeks) radiation therapy (RT) and concurrent temozolomide (TMZ) at a standard targeted dose of 75 mg/m2/day. The study cycle of TMZ comprises a targeted dose of 150-200mg/m2/day for 5 days every 4 (+2) weeks for up to 12 cycles (patients with unmethylated MGMT gene promoter will receive only cycle 1). All patients will receive up to a total of 10 DC vaccines called pp65 CMV dendritic cells (DC). Dendritic Cell (DC) vaccines #1-3 will be given every two weeks, thus delaying the initiation of TMZ cycle 2 for patients receiving TMZ. All remaining TMZ/vaccine cycles will be 4 (+2) weeks in length. After the first 3 DC vaccines given during Cycle 1 of TMZ, the remaining DC vaccine injections are given on Day 21 (+/- 2 days) of each TMZ cycle. Subjects with unmethylated MGMT will only receive one cycle of adjuvant TMZ; however, their vaccine schedule will follow the same 4 (+ 2) week TMZ cycle schedule. Following RT, patients will be randomized into 1 of 3 groups. Groups 1 and 2 will be blinded. The groups differ in the type of pre-conditioning received prior to DC vaccine #4; additionally, Group 3 will be receiving infusions of varlilumab 7 days prior to and with vaccine #1 and 7 days prior to vaccine #3+. The pre-conditioning for each group is as follows: Group 1: Unpulsed DC pre-conditioning prior to DC vaccine #4; Group 2: Tetanus-diphtheria (Td) pre-conditioning prior to DC vaccine #4; Group 3: Td pre-conditioning prior to DC vaccine #4 and varlilumab infusion at 7 days prior to each DC vaccine (except DC vaccine #2) with Td pre-conditioning prior to vaccine #4.

Key Details

Gender

All

Age Range

18 Years - Any

Study Type

INTERVENTIONAL

Enrollment

43

Start Date

2020-08-26

Completion Date

2026-03

Last Updated

2025-04-15

Healthy Volunteers

No

Conditions

Interventions

BIOLOGICAL

Human CMV pp65-LAMP mRNA-pulsed autologous DCs

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.

DRUG

Temozolomide

Temozolomide is a standard chemotherapy given to all enrolled patients at a targeted dose of 150-200mg/m2/d for 5 days every 4 (+ 2) weeks for up to 12 cycles (patients with unmethylated MGMT gene promoter will receive only cycle 1)

BIOLOGICAL

Varlilumab

Varlilumab is an agonist anti-CD27 monoclonal antibody

BIOLOGICAL

Td

A single dose of Td toxoid (1 flocculation unit, Lf, in 0.4 mLs) administered to a single side of the groin given intradermally

BIOLOGICAL

Unpulsed DCs

Patients in Group I will receive 1 x 10\^6 autologous unpulsed DCs in saline administered to a single side of the groin intradermally 1 day before the fourth vaccine.

Locations (1)

Duke University Medical Center

Durham, North Carolina, United States