NCT06514898

Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade in Patients With Medulloblastoma

MATCHPOINT - Medulloblastoma Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 4 Years – 30 Years
• Healthy volunteers: Not accepted

Summary

This is a pilot study in a small number of children and young adults with suspected recurrent/progressive medulloblastoma (MB) looking at the feasibility and safety of adoptive cell therapy plus PD-1 blockade.

Detailed description

This is a single-site, single arm, unblinded, uncontrolled pilot study to evaluate the feasibility and safety of ACT + PD-1 blockade in children and young adults with suspected recurrence/progression of Group 3 or 4 (non-SHH/non-WNT) medulloblastoma since completion of definitive focal +/- craniospinal irradiation who are a candidate for surgical resection or biopsy. After a screening consent is obtained, subjects will undergo standard of care resection for tumor debulking or biopsy for confirmatory diagnosis of disease progression. Tumor tissue will be collected during surgery for tumor debulking or biopsy for total tumor RNA and generation of investigational DC vaccine in parallel. Following biopsy and confirmatory pathologic diagnosis of recurrent MB, patients will be enrolled in the treatment phase of the trial. After surgery, patients will undergo a 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 post-surgical salvage chemotherapy regimen. Salvage therapy prescribed by treating neuro-oncologist 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 bi-weekly 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 salvage therapy will resume with monthly TTRNA-DC vaccines for an additional 1-3 cycles until ex vivo expanded T cells are manufactured and released from the UF cGMP facility. For ACT, patients will undergo non-myeloablative conditioning with cyclophosphamide/fludarabine followed by infusion of ex vivo expanded tumor-reactive lymphocytes at 3 x 108 cells/Kg, infusion of autologous CD34+ HSCs (targeted dose of 2 x 106 CD34+ HSCs/Kg), PD-1 blockade and three biweekly intradermal TTRNA-DC vaccines to boost T cell engraftment and expansion. 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 intravenous infusion of ex vivo expanded tumor-reactive T cells, and a. single intravenous infusion of autologous HSCs; and PD-1 blockade IV starting with ACT continuing for up to 2 years as long as tolerable and without disease progression. All patients will receive a full Td booster (5 Lf) IM vaccine prior to Vaccine #1, regardless of booster history. All patients will undergo vaccine site pretreatment with a one-fifth dose of Td (1 Lf) intradermally, at the site of planned DC vaccine, 4-24 hours prior to vaccines #3, #5, #7 and #9.

Conditions

• Recurrent Group 3 Medulloblastoma
• Recurrent Group 4 (Non-SHH/Non-WNT) Medulloblastoma

Interventions

Type	Name	Description
BIOLOGICAL	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. 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	TTRNA-xALT	All participants will receive a single infusion of T-cells.
DRUG	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, #5, #7 and #9.
BIOLOGICAL	autologous HSCs	All participants will receive a single intravenous infusion of autologous HSCs.
DRUG	Pembrolizumab	Participants will receive PD-1 blockade IV starting with ACT continuing for up to 2 years as long as tolerable and without disease progression.

Timeline

• Start date: 2025-05-05
• Primary completion: 2027-09-01
• Completion: 2028-12-01
• First posted: 2024-07-23
• Last updated: 2026-04-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study