Ignite Creation Date:
2024-10-26 @ 3:35 PM
Last Modification Date:
2024-10-26 @ 3:35 PM
Study NCT ID:
NCT06514898
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-07-17
Brief Title:
Adoptive T Cell Therapy DC Vaccines and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade in Patients With Medulloblastoma
Sponsor:
None
Organization:
None
Study Overview
Official Title:
MATCHPOINT - Medulloblastoma Adoptive T Cell Therapy DC Vaccines and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MATCHPOINT
Brief Summary:
This is a pilot study in a small number of children and young adults with relapsedprogressive 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 recurrenceprogression of Group 3 or 4 non-SHHnon-WNT medulloblastoma since completion of definitive focal - craniospinal irradiation who are a candidate for surgical resection or biopsy
After a screening consent is obtained for the collection of tumor sample 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 obtaining informed consent
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 chemotherapy 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 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 salvage chemotherapy 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 cyclophosphamidefludarabine followed by infusion of ex vivo expanded tumor-reactive lymphocytes at 3 x 108 cellsKg infusion of autologous CD34 HSCs targeted dose of 2 x 106 CD34 HSCsKg 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 4-24 hours 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
After a screening consent is obtained for the collection of tumor sample 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 obtaining informed consent
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 chemotherapy 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 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 salvage chemotherapy 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 cyclophosphamidefludarabine followed by infusion of ex vivo expanded tumor-reactive lymphocytes at 3 x 108 cellsKg infusion of autologous CD34 HSCs targeted dose of 2 x 106 CD34 HSCsKg 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 4-24 hours 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None