MedulloblastomaPhase 2Re-MATCHNCT01326104
Vaccine Immunotherapy for Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor
A Phase 2 study testing TTRNA-xALT and TTRNA-DCs in people with Medulloblastoma and Neuroectodermal Tumor, run by University of Florida at 3 sites in United States.
Trial summary
Immunotherapy is a specific approach to treating cancer that has shown promise in adult patients for the treatment of melanoma, malignant brain tumors, and other cancers. The study investigators will use the experience they have gained from these studies to try to improve the outcome for children affected by a… Read more about this study
- Who is it for?
- Ages Up to 30 years
- Conditions the study is for
- Medulloblastoma, Neuroectodermal Tumor
- What is being tested?
- TTRNA-xALT and TTRNA-DCs
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 3 sitesUnited States
- Study dates
- 7 Sep 2010to 28 Mar 2025
- Phase
- Phase 2
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 Up to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Screening:
- Age ≤ 30 years of age.
- Suspected first recurrence/progression of MB/PNET since completion of definitive focal +/- craniospinal irradiation. Disease progression prior to receiving definitive focal +/- craniospinal irradiation will not disqualify patients from enrollment if they have subsequently failed definitive radiotherapy and are at first recurrence/progression at time of enrollment. 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.
- Re-MATCH Protocol:
- Patients must have histologically confirmed recurrent MB/PNET that is a first relapse/progression after completion of definitive radiotherapy +/- craniospinal irradiation. Patients with a first relapse/progression who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (ie. Gorlin's syndrome or NF1 mutation) are eligible for enrollment.
- Patients with neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
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- Karnofsky Performance Status of ≥ 50% or Lansky Performance Score of ≥ 50.
- Absolute Neutrophil Count (ANC) ≥ 1000/µl (unsupported).
- Platelets ≥ 100,000/µl (unsupported).
- Hemoglobin > 8 g/dL (may be supported).
- Serum creatinine ≤ upper limit of institutional normal
- Bilirubin ≤ 1.5 times upper limit of normal for age.
- Serum Glutamic Oxaloacetic Transaminase (ALT) ≤ 3 times institutional upper limit of normal for age.
- Serum Glutamic Oxaloacetic Transaminase (AST) ≤ 3 times institutional upper limit of normal for age.
- Patients of childbearing or child-fathering potential must be willing to use a medically acceptable form of birth control, which includes abstinence, while being treated on this study.
- Patient or patient guardian consent to peripheral blood stem cell (PBSC) and/or bone marrow harvest following registration if PBSC or bone marrow (CD34 count of at least 2x10^6/kg) has not been previously stored and available for use.
- Signed informed consent according to institutional guidelines must be obtained prior to registration.
Who cannot join
- Pregnant or need to breast feed during the study period.
- Active infection requiring treatment or an unexplained febrile (> 101.5F) illness.
- Known immunosuppressive disease, human immunodeficiency virus infection, or carriers of Hepatitis B or Hepatitis C virus.
- Patients with active renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), or pulmonary disease.
- Patients receiving concomitant immunosuppressive agents for medical condition.
- Patients who need definitive radiotherapy for treatment of recurrent MB/PNET. Focal boost radiotherapy may be delivered prior to immunotherapy if required for local control.
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- Patients receiving any other concurrent anticancer or investigational drug therapy.
- Patients with any clinically significant unrelated systemic illness (serious infections or significant cardiac, pulmonary, hepatic or other organ dysfunction).
- Patients with inability to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of Florida
Gainesville, Florida, 32610
Children's Hospital Los Angeles
Los Angeles, California, 90027
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Recurrent Medulloblastoma and Primitive Neuroectodermal Tumor Adoptive T Cell Therapy During Recover From Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation
Immunotherapy is a specific approach to treating cancer that has shown promise in adult patients for the treatment of melanoma, malignant brain tumors, and other cancers. The study investigators will use the experience they have gained from these studies to try to improve the outcome for children affected by a recurrent brain tumor.
Approximately 35 patients with first recurrence of medulloblastoma (reMB)/supratentorial primitive neuroectodermal tumors (PNETs) will be treated with tumor-specific immune cells and dendritic cell vaccines to see what impact they have on the tumor.
Read the detailed description
Malignant brain tumors now represent the most frequent cause of cancer death in children. Despite aggressive and highly toxic multi-modality therapy including surgery, craniospinal radiation, and high-dose chemotherapy coupled with peripheral blood stem cell transplantation, almost half the children diagnosed with the most common malignant brain tumors, medulloblastoma (MB) and primitive neuroectodermal tumors (PNET), will still die from recurrent disease. Furthermore, survivors are often left with severe and lifelong treatment-associated cognitive and motor deficits. The development of more effective and tumor-specific therapies that will not add further toxicity to existing treatments is paramount in improving clinical outcomes for children affected by MB/PNETs. Immunotherapy targeting tumor-specific antigens expressed within brain tumors is a modality potentially capable of meeting this clear and urgent need.
Despite considerable advancements and promising clinical results observed in immunotherapy trials directed against adult malignant brain tumors, efforts in the immunologic treatment of pediatric brain tumors have been limited to relatively few notable studies. This is due, at least in part, to the often limited viable tumor tissue available for tumor cell-based vaccine preparations, and the lack of identification of consistently expressed tumor-specific antigens within these cancers.
The use of total tumor RNA (TTRNA)-loaded dendritic cells (DCs) was pioneered at Duke University, as a novel platform for inducing potent immunologic responses against the variety of uncharacterized and patient-specific antigens present within malignant tumor cells. Duke demonstrated that sufficient RNA for clinical vaccine preparations can be amplified with high fidelity using existing molecular technologies from as few as 500 isolated pediatric and adult brain tumor cells, thus allowing vaccine preparation from surgical biopsies and even microdissected archival tumor specimens.
Immunotherapy administered during recovery from chemotherapy may have tremendous advantages, as adoptive cellular therapy following lymphodepletive conditioning regimens has emerged as the most effective treatment strategy for advanced and refractory melanoma. Our hypothesis is that DC + ex vivo expanded Autologous Lymphocyte Transfer (xALT) therapy targeting recurrent MB/PNETs during recovery from myeloablative chemotherapy will be safe and will prolong survival in children and young adults with recurrent MB/PNETs.
In this study, the investigators will treat patients with first recurrence reMB/PNETs after completion of definitive radiation therapy with autologous tumor-specific T cell immunotherapy (TTRNA-xALT) plus TTRNA-loaded dendritic cell vaccine.
Following surgical resection, biopsy, or cytology examination with confirmatory pathologic diagnosis, patients will be enrolled into Group A (high-dose chemotherapy or HDC) or Group B (non-myeloablative or NMA salvage chemotherapy) based on eligibility for HDC. Patients with localized relapse and have not failed HDC+ peripheral blood stem cell transplant (PBSCT) previously will be enrolled into Group A. Patients with disseminated disease, have previously failed HDC+PBSCT, or are otherwise considered poor candidates for HDC based on overall health status, but otherwise meet eligibility criteria, will be enrolled into Group B. All patients will receive DC + xALT therapy.
- Conditions
- Medulloblastoma, Neuroectodermal Tumor
- Being tested
- TTRNA-xALT, TTRNA-DCs
- Keywords
- Medulloblastoma, Primitive Neuroectodermal Tumor
- Medical subject headings
- Medulloblastoma, Neuroectodermal Tumors, Neuroectodermal Tumors, Primitive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TTRNA-xALTBiological
TTRNA-xALT 3 x 10^7/kg by intravenous injection once.
TTRNA-DCsBiological
TTRNA-DCs 1 x 10^7 by intradermal injection every 2 weeks for 3 total doses.
| Study group | Role | What they receive |
|---|---|---|
| Group A | Experimental | High dose chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. Receives: Biological: TTRNA-xALT; Biological: TTRNA-DCs |
| Group B | Experimental | NMA Salvage chemotherapy plus peripheral blood stem cell transplant followed by TTRNA-xALT and TTRNA-DCs. Receives: Biological: TTRNA-xALT; Biological: TTRNA-DCs |
What is being measured
The primary outcome is the main question the study is designed to answer.
12 Month Progression-free Survival (PFS-12)
PFS-12 is the number of participants (%) with PFS at 12 months. PFS is defined as time interval from date of first DC vaccine to date of progression (death is also treated as progression) or censoring, whichever happens first.
The PFS-12 of Historical Benchmark is 33%. The granular PFS of Historical Bechmark is 4,16, 5, 12, 14, 7, 5, 5, 12, 9, 24 and 13 months (Gururangan et al,. Neuro Oncol. 2008, Table 3)
Measured: up to 12 months
Secondary outcomes (18)
Objective Radiographic Response Rate
Objective Response Rate (ORR), defined as the proportion of subjects who show partial or complete response (CR+PR) to therapy, SD (stable disease), and PD (progressive disease) or not assessable, using RECIST criteria based on their best overall response over 8 weeks when comparing pre-ACT vs. post-ACT MRI.
Measured: Baseline MRI (prior to Adoptive Cellular Therapy (ACT)) compared to post-ACT MRI (approximately 8 weeks post-baseline MRI)
Change in Cytokine Profile for IFNg
We will measure serum cytokines in peripheral blood pre and post ACT therapy for patients in Arm A and Arm B. We will compare baseline (pre-ACT) to post treatment (both TTRNA-xALT and TTRNA-DCs vaccines administered) changes for each arm. Longitudinal difference baseline to Day 14 and 28 with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Overall Survival (OS) Rate
12-month OS calculated based on benchmark.
OS-12 is the proportion of participants with OS at 12 months.
Measured: baseline up to 12 months
Change in Type 1 Interferon
We will measure change in cellular immunity in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to Day 28 (including Day 14) with each patient. OS Univariable Cox Regression with Change in Cellular Immunity was applied. The Hazard Ratio with 95% CI reported.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Type 2 Interferon
We will measure change in cellular immunity in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to Day 28 (including Day 14) with each patient. OS Univariable Cox Regression with Change in Cellular Immunity was applied. The Hazard Ratio with 95% CI reported.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Percentage of CD8 Naive T Cells in PBMC
We will measure change in lymphocyte phenotype in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline (pre-treatment) to 28 days with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Cytokine Profile for IL10
We will measure serum cytokines in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to Day 14 and 28 with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Cytokine Profile for IL12p70
We will measure serum cytokines in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to Day 14 and 28 with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Cytokine Profile for IL2
We will measure serum cytokines in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to Day 14 and 28 with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Cytokine Profile for IL4
We will measure serum cytokines in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to Day 14 and 28 with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Cytokine Profile for IL6
We will measure serum cytokines in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to Day 14 and 28 with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Cytokine Profile for TNFa
We will measure serum cytokines in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to Day 14 and 28 with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in TLR Activation Status
We will measure change in TLR activation status in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to Day 14 and 28 with each patient serving as own control using mixed linear effect model. We quantified pathway activity using GSVA applied to normalized RNA-seq expression data. The enrichment score for each sample was defined as the maximum deviation from zero of this running sum, yielding a dimensionless GSVA score that represents the relative coordinated up- or down-regulation of TLR pathway genes within that sample compared to the background transcriptome. Higher GSVA score represents upregulation and lower GSVA score represents downregulation. There is no clinical relevance threshold.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Percentage of CD8 Memory T Cells in PBMC
We will measure change in lymphocyte phenotype in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to 28 days with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Percentage of CD4 Naive T Cells in PBMC
We will measure change in lymphocyte phenotype in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to 28 days with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Percentage of CD4 Memory T Cells in PBMC
We will measure change in lymphocyte phenotype in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to 28 days with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Percentage of Treg T Cells in PBMC
We will measure change in lymphocyte phenotype in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to 28 days with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Change in Percentage of NK Cells in PBMC
We will measure change in lymphocyte phenotype in peripheral blood pre and post therapy for patients in Arm A and Arm B. We will compare baseline to post treatment changes for each arm. Longitudinal difference baseline to 28 days with each patient serving as own control using mixed linear effect model.
Measured: baseline prior to immunotherapy to 28 days post-vaccine #1 (both TTRNA-xALT and TTRNA-DCs vaccines administered)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2011 (estimated)
- Study start7 Sep 2010
- Primary completion28 Mar 2020
- Study completion28 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Sponsor
- Investigators
- Duane Mitchell, MD, PhD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01326104
- Sponsor's protocol ID
- IRB201500502
- Other IDs
- W81XWH-10-1-0089, CDMRP-PRO93877, OCR13166
- Acronym
- Re-MATCH
- Status last verified
- Apr 2025
- First submitted
- 22 Jul 2010
- Last updated
- 13 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Collins RRJ, Florke Gee RR, Tozandehjani S, Bayat T, Hoyos Sanchez MC, Gutierrez JSS, Breznik B, Lee AK, Peters ST, Connelly JP, Pruett-Miller SM, Roussel MF, Rakheja D, Tillman HS, Potts PR, Fon Tacer K. Melanoma antigens in pediatric medulloblastoma contribute to tumor heterogeneity and species-specificity of group 3 tumors. Acta Neuropathol Commun. 2025 Jul 28;13(1):164. doi: 10.1186/s40478-025-02055-3.
PubMed 40721826