A Phase I/II Clinical Trial on the Per-operative Intratumoral Administration of Myeloid Dendritic Cells Plus Ipilimumab and Nivolumab, Followed by Repeated Intracavitary Plus Intravenous Administration of Nivolumab in Patients With Recurrent Glioblastoma.

Sponsor
Universitair Ziekenhuis Brussel
Study ID
NCT03233152
Phase
PHASE1/PHASE2
Status
Active Not Recruiting

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Ipilimumab (YervoyTM, 50 mg/10 mL solution) — DRUG
    Ipilimumab will be administered by at the end of the neurosurgical resection procedure at a dose of injection of 10 mg (: 2 ml of YervoyTM, 50 mg/10mL vial). Injections will be performed manually using a 100 μ-liter dispensing syringe. Twenty needle tracks will dispense the ipilimumab solution within the brain tissue lining the resection cavity. The region suspect on preoperative MRI of the brain to be invaded by glioblastoma cells but not amenable to safe resection will be targeted by adjacent needle tracks through which up to 2 cm of depth a volume of 100 μl per needle track will be injected (: in total 20 needle tracks will be performed). This methodology has been applied previously within the context of phase III clinical trials with sitimagene ceradenovec.
  • Nivolumab (OpdivoTM, 40 mg/4mL solution) — DRUG
    First administration of 10 mg of nivolumab by the intravenous route should be administered within 24 hours prior to the planned neurosurgical resection. Administrations of 10 mg nivolumab (OpdivoTM, 40 mg/4mL solution) will be by a 15 minutes intravenous infusion on days 15, 29, 43, 57, and 71 (or up to ± 3 days before or after the scheduled date if necessary).
  • Autologous CD1c(BDCA-1)+ /CD141(BDCA-3)+ myDC — BIOLOGICAL
    Autologous CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC will be isolated from PBMC obtained from the leukapheresis. These are injected in the neighbouring brain tissue post tumor resection.

Study Details

Phase I/II clinical trial on the per-operative intra-tumoral administration of myeloid dendritic cells plus ipilimumab and nivolumab, followed by repeated intracavitary administration of ipilimumab and nivolumab plus intravenous administration of nivolumab in patients with recurrent glioblastoma. The aim of this clinical trial is to exploit the potential synergy of combined intra-tumoral CTLA-4 and autologous CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC and systemic PD-1 blockade while minimizing the risk for increased immune-related toxicity by intratumoral administration of the CTLA-blocking mAb ipilimumab following the resection of the recurrent glioblastoma.

Key Dates

Start date
Nov 17, 2016
Status verified
Nov 2025
Primary completion
Nov 17, 2026
Completion
Nov 17, 2026

Study Design

Enrollment
110 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: ipilimumab + nivolumab + CD1c (BDCA-1)+ myDC and CD141 (BDCA-3)+ myDC
    Phase I CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC dose escalation (: 3 predefined dose levels) part of the study: to document the safety of peroperative injection of an escalating number of autologous CD1c(BDCA-1)+/CD141(BDCA-3)+ myDC plus IT injection of nivolumab and ipilimumab, following tumor resection. Phase II part of the study: to document the anti-tumor activity of peroperative injection of a defined number of autologous CDC1(BDCA-1)+/CD141(BDCA-3)+myDC. Ipilimumab (YervoyTM, 50 mg/10 mL) and Nivolumab (OpdivoTM, 40 mg/4mL solution) will be administered peroperatively at a dose of injection of 10 mg (2 ml of YervoyTM, 50 mg/10mL vial). as well as intracavitary on days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169. 10 mg Nivolumab by the intravenous route will be administered by a 15 minutes intravenous infusion on days 15, 29, 43, 57, 71, 85, 99, 113, 127, 141, 155 and 169. (or up to ± 3 days before or after the scheduled date if necessary).

Primary Outcome Measure

Progression-free survival (PFS) [ Time Frame: up to 30 weeks ]

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