Recurrent Group 3 MedulloblastomaPhase 1MATCHPOINTNCT06514898
Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade in Patients With Medulloblastoma
A Phase 1 study testing TTRNA-DC vaccines with GM-CSF, TTRNA-xALT and Td vaccine in people with Recurrent Group 3 Medulloblastoma and Recurrent Group 4 (Non-SHH/Non-WNT) Medulloblastoma, run by University of Florida at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 30 years
- Conditions the study is for
- Recurrent Group 3 Medulloblastoma, Recurrent Group 4 (Non-SHH/Non-WNT) Medulloblastoma
- What is being tested?
- TTRNA-DC vaccines with GM-CSF, TTRNA-xALT and Td vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 2 sitesUnited States
- Study dates
- 5 May 2025to 1 Dec 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Children and young adults ages 4-30 years with suspected recurrence/progression of Group 3 or 4 (non-SHH/non-WNT) MB since completion of definitive focal +/- craniospinal irradiation who are a candidate for surgical resection or biopsy. Of the 6 evaluable subjects, a minimum of 3 slots must be reserved for patients with confirmed Group 4 MB. Patients who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (i.e. Gorlin's syndrome or NF1 mutation) are eligible for enrollment at first disease recurrence/progression.
- Patients must currently be prescribed and approved to receive pembrolizumab therapy (patients who have progressed on anti-PD-1 targeting therapy but are otherwise eligible may be enrolled to receive combination with immunotherapy. Patients who have been previously treated with anti-PD-1 targeting therapy alone or in combination with other agents and discontinued for reasons other than toxicity may be enrolled).
- Must be a candidate for surgery/biopsy Or tumor tissue obtained clinically, has been previously stored in a qualified site in a manner suitable for tumor RNA extraction and amplification and sample is made available to the PI.
- Karnofsky or Lansky Performance Status (KPS) ≥ 60% (KPS for > 16 years of age) or Lansky performance Score (LPS) of ≥ 60 (LPS for < 16 years of age)
- Adequate bone marrow and organ function as defined below:
- ANC ≥ 1,000/mcL (unsupported)
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- Platelets ≥ 100,000/mcL (unsupported for at least 3 days)
- Hemoglobin ≥ 9 g/dL (may be supported)
- Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine > 1.5 x IULN
- Serum total bilirubin ≤ 1.5 x IULN for age OR Direct bilirubin ≤ IULN for patients with total bilirubin > 1.5 x IULN for age
- AST (SGOT) and ALT (SGPT) ≤ 3 x IULN for age
- Cardiac shortening fraction ≥27% or LVEF ≥50% by echocardiogram
- Adequate pulmonary function defined as baseline pulse oximetry of ≥92% on room air
- For females of childbearing potential, negative serum pregnancy test at enrollment
- For women of childbearing potential (WOCBP) must be willing to use acceptable contraceptive methods to avoid pregnancy throughout the study and for at least 24 weeks after the last dose of study drug.
- or For males with female partners of childbearing potential must agree to use physician-approved contraceptive methods (e.g., abstinence, condoms, vasectomy) throughout the study and should avoid conceiving children for 24 weeks following the last dose of study drug.
- Signed informed consent by patient and/or legally authorized representative
Who cannot join
- this study:
- Prior discontinuation of PD-1 inhibitor treatment due to toxicity.
- Corticosteroids equivalent to ≥ 4mg dexamethasone daily.
- Known HIV, Hepatitis B, or Hepatitis C seropositive.
- Known active infection or immunosuppressive disease.
- Known autoimmune disease requiring medical management with immunosuppressant.
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- Pregnancy or lactation, due to possible adverse effects on the developing fetus or infant.
- Treatment with another investigational drug or other intervention within 30 days prior to projected first dose of study treatment (Priming phase with TTRNA-DC).
- Known severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization.
- Transmural myocardial infarction within the last 6 months.
- Acute bacterial or fungal infection requiring intravenous antibiotics at time of enrollment.
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy.
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
- Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Florida Health
Gainesville, Florida, 32608
Marcia Hodik, RN, 352-273-9000, marcia.hodik@neurosurgery.ufl.edu
John Ligon, MD
- Not yet recruiting
Children's National Hospital
Washington D.C., District of Columbia, 20010
Elizabeth Paronett, MSHS, 202-476-5551
Eugene Hwang, MD
About this study
Official title: MATCHPOINT - Medulloblastoma Adoptive T Cell Therapy, DC Vaccines, and Hematopoietic Stem Cells Combined With Immune checkPOINT Blockade
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.
Read the detailed description
This is a multi-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.
- Being tested
- TTRNA-DC vaccines with GM-CSF, TTRNA-xALT, Td vaccine, autologous HSCs, Pembrolizumab
- Medical subject headings
- Medulloblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TTRNA-DC vaccines with GM-CSFBiological
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)
TTRNA-xALTBiological
All participants will receive a single infusion of T-cells.
Td vaccineDrug
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.
autologous HSCsBiological
All participants will receive a single intravenous infusion of autologous HSCs.
PembrolizumabDrug
Participants will receive PD-1 blockade IV starting with ACT continuing for up to 2 years as long as tolerable and without disease progression.
| Study group | Role | What they receive |
|---|---|---|
| Adoptive Cellular Therapy (ACT) + PD-1 blockade with pembrolizumab | Experimental | ACT + PD-1 blockade consists of the intravenous delivery of ex vivo expanded tumor-reactive lymphocytes and autologous hematopoietic stem cells (HSCs) with concomitant tumor RNA-pulsed DC vaccines followed by intravenous delivery of PD-1 blocking antibodies. Receives: Biological: TTRNA-DC vaccines with GM-CSF; Biological: TTRNA-xALT; Drug: Td vaccine; Biological: autologous HSCs; Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with immunotherapy-related dose-limiting toxicities after treatment with TTRNA-DCs, TTRNA-xALT and HSCs plus PD1 blockade
Number of subjects with immunotherapy-related dose-limiting toxicities including 1) Grade III or greater non-neurologic toxicity; 2) Grade III neurologic toxicity that does not improve to Grade II or better within 5 days; or 3) Grade IV neurologic toxicity.
For the purposes of evaluating the safety of ACT combined with PD-1 blockade, dose limiting toxicities will be assessed during the period beginning with administration of ex vivo expanded tumor-reactive (TTRNA- xALT) through 2 weeks post TTRNA -DC vaccine #9.
Safety will be defined as < 1 DLT out of six enrolled and treated subjects.
Measured: enrollment to completion of DLT window; up to 12 months
Number of enrolled participants who receive qualified immunotherapy products out of the total number of participants enrolled.
Feasibility will be defined as capacity to enroll, manufacture, and administer qualified immunotherapy products (TTRNA-DCs, TTRNA-xALT and HSCs) to at least 66.7% of enrolled subjects.
Measured: enrollment up to 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2024
- Study start5 May 2025
- Primary completion1 Sep 2027 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Group 3 MedulloblastomaStudies of the same condition, open and under way.
- More trials run by University of FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Children's National Research Institute
- Responsible party
- Sponsor
- Investigators
- Duane Mitchell, MD, PhD, Study chair, University of FloridaJohn Ligon, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06514898
- Sponsor's protocol ID
- IRB202400861-A
- Other IDs
- OCR45772
- Acronym
- MATCHPOINT
- Status last verified
- Aug 2026
- First submitted
- 17 Jul 2024
- Last updated
- 7 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No