NCT06254326

ADAGiO: Adoptive Cellular Therapy for the TreAtment of Recurrent OliGodendrogliOma (OG) Adult Patients

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 18 Years – 89 Years
• Healthy volunteers: Not accepted

Summary

This study will enroll 6 DLT evaluable subjects (up to 12 patients total) where we will evaluate feasibility and safety of adoptive cellular therapy combined with IDH1/2 inhibitors in patients with recurrent or progressive oligodendroglioma WHO grade 2 and WHO grade 3.

Detailed description

After screening consent, subjects will undergo standard of care resection or biopsy for confirmatory diagnosis of disease progression and aseptic collection of tumor material for DNA and RNA extraction and sequencing, amplification, and loading of autologous DCs. Following biopsy and confirmatory pathologic diagnosis, eligible patients will be enrolled in treatment. After surgery, patients will undergo a G-CSF mobilized pheresis to collect PBMCs for DC generation and CD34+ HSCs. Amplified tumor RNA obtained from surgically resected or biopsied specimens will be used to generate total tumor RNA-pulsed DCs (TTRNA-DCs) manufactured while patients initiate salvage chemotherapy regimen after surgery. Salvage chemotherapy with IDH1/2 inhibitor will initiate 1-2 weeks after G-CSF mobilized leukapheresis for 1-3 cycles after which, treatment cycles will be paused, and the patients will receive 3 priming TTRNA-DCs vaccines every 2 weeks and undergo a non-mobilized leukapheresis to collect vaccine-boosted lymphocytes for ex vivo T cell expansion and generation of additional TTRNA-DC vaccines. Treatment with IDH1/2 inhibitor will resume with monthly TTRNA-DC vaccines for an additional 1-3 cycles until ex vivo expanded T cells are manufactured. For ACT, patients will undergo non-myeloablative conditioning with cyclophosphamide /fludarabine. The total immunotherapy regimen will consist of up to 9 intradermal DC vaccines (three -bi-weekly (q2 weeks) for priming, monthly for additional 2-3 cycles during T cell expansion, and three bi-weekly during T cell engraftment), a single i.v. infusion of ex vivo expanded tumor-reactive T cells, and a i.v. single infusion of autologous HSCs. The duration of treatment from enrollment to completion of DLT window is anticipated to be 7 to 9 months.

Conditions

• Recurrent Oligodendroglioma
• Progressive Oligodendroglioma

Interventions

Type	Name	Description
BIOLOGICAL	TTRNA-DC vaccines with GM-CSF	Participants will receive up to 9 intradermal DC vaccines (three -bi-weekly (q2 weeks) for priming, monthly for additional 2-3 cycles during T cell expansion, and three bi-weekly during T cell engraftment
BIOLOGICAL	Autologous Hematopoietic Stem cells (HSCs)	Participants will receive a single infusion of autologous CD34+ HSCs
BIOLOGICAL	TTRNA-xALT	Participants will receive a single infusion of ex vivo expanded tumor-reactive T cells
DRUG	Td vaccine	All patients will receive a full Td booster IM vaccine 4-24 hours prior to Vaccine #1 and vaccine site pretreatment with a one-fifth dose of Td intradermally, at the site of planned vaccine, 4-24 hours prior to vaccines #3, #5, #7 and #9.

Timeline

• Start date: 2024-09-19
• Primary completion: 2027-12-01
• Completion: 2028-06-01
• First posted: 2024-02-12
• Last updated: 2026-03-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study