Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas

Study Purpose

It is believed that the body's immune system protects the body by attacking and killing tumor cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they recognize special proteins on the surface of tumors. In most patients with advanced cancer, T-cells are not stimulated enough to kill the tumor. In this research study, we will use a patient's tumor to make a vaccine which we hope will stimulate T-cells to kill tumor cells and leave normal cells alone. High grade gliomas (HGGs) are very aggressive and difficult for the body's immune system to attack. Before T-cells can become active against tumor cells, they require strong stimulation by special "stimulator" cells in the body called Dendritic Cells (DCs) which are also part of the immune system. DCs can recognize the cancer cells and then activate the T lymphocytes, and create this strong stimulation. The purpose of this research study is to learn whether anti-tumor T-cells and anti-tumor DC vaccines can be given safely. Most importantly, this study is also to determine whether the T-cells and DC vaccines can stimulate a person's immune system to fight off the tumor cells in the brain.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 3 Years - 21 Years
Gender All
More Inclusion & Exclusion Criteria

Screening Eligibility:

  • - Patients with histologically confirmed WHO Grade III or IV malignant glioma - Scheduled for definitive surgical resection of suspected HGG (biopsy only subjects are not eligible for this study) Post-Surgical Resection Eligibility - Histologically confirmed WHO Grade III or IV malignant glioma - Residual post-surgical disease burden < 3 cm as defined by longest perpendicular diameter of contrast enhancing tumor on post-operative MRI Karnofsky Performance Status (KPS) of > 60% (KPS for > 16 years of age) or Lansky performance Score (LPS) of ≥ 60 (LPS for ≤ 16 years of age) assessed within 2 weeks prior to registration - Bone Marrow: ANC (Absolute neutrophil count) ≥ 1000/µl (unsupported); Platelets ≥ 100,000/µl (unsupported for at least 3 days); Hemoglobin > 8 g/dL (may be supported) - Renal:Serum creatinine ≤ upper limit of institutional normal Hepatic: Bilirubin ≤ 1.5 times upper limit of institutional normal for age.
SGPT (ALT) ≤ 3 times upper limit of institutional normal for age. SGOT (AST) ≤ 3 times upper limit of institutional normal for age.
  • - Signed informed consent according to institutional guidelines.
  • - Patient or patient guardian consent to PBSC harvest following registration.
  • - Subjects of childbearing or child-fathering potential must be willing to use medically acceptable forms of birth control while being treated on this study.
  • - Subjects with post-surgical neurological deficits should have deficits that are stable for a minimum of 1 week prior to registration.
Prior to 1st Vaccine
  • - Off corticosteroids or weaning to a minimal/stable dose of replacement steroids ≤ 4 mg/day within 1 week of scheduled DC vaccination.

Exclusion Criteria:

  • - HGG biopsy only subjects are not eligible for this study - Midline unresectable tumors - Gliomatosis Cerebri - Residual post-surgical disease burden > 3 cm as defined by longest perpendicular diameter of contrast enhancing tumor on MRI.
  • - Pregnant or need to breast feed during the study period (Negative serum pregnancy test required).
  • - Known autoimmune or immunosuppressive disease or human immunodeficiency virus infection.
  • - Subjects with significant renal, cardiac (congestive cardiac failure, myocardial infarction, myocarditis), pulmonary, hepatic or other organ dysfunction.
  • - Subjects who require corticosteroids above physiologic doses (>4mg/day or equivalent dexamethasone).
  • - Severe or unstable concurrent medical conditions.
  • - Prior allergic reaction to TMZ, GM-CSF, or Td - Subjects who are unwilling or unable to receive treatment and undergo follow-up evaluations at the enrolled Sunshine Project Consortium treatment site.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03334305
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Florida
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Elias Sayour, MD, PhDDuane Mitchell, MD, PhD
Principal Investigator Affiliation University of FloridaUniversity of Florida
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherOtherNIHOtherNIH
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Malignant Glioma, High Grade Glioma
Additional Details

It is believed that the body's immune system protects the body by attacking and killing tumor cells. T-lymphocytes (T-cells) are part of the immune system and can attack when they recognize special proteins on the surface of tumors. But in most patients with advanced cancer, T-cells are not stimulated enough to kill the tumor. In this research study, we will use your tumor to make a vaccine which we hope will stimulate your T-cells to kill tumor cells and leave your normal cells alone. High grade gliomas (HGGs) are very aggressive and difficult for the body's immune system to attack. Before T-cells can become active against tumor cells, they require strong stimulation by special "stimulator" cells in the body called Dendritic Cells (DCs) which are also part of the immune system. DCs can recognize the cancer cells and then activate the T lymphocytes, and create this strong stimulation. The purpose of this research study is to learn whether anti-tumor T-cells and anti-tumor DC vaccines can be given safely. Most importantly, this study is also to determine whether the T-cells and DC vaccines can stimulate your immune system to fight off the tumor cells in your brain. When the vaccine for this study is made, dendritic cells will be loaded with genetic material called RNA (ribonucleic acid) from your tumor to stimulate the dendritic cells. The vaccine has two components given at different times after chemoradiation and throughout chemotherapy cycles. The first part, the DC vaccine, involves RNA loaded dendritic cells that are given under the skin at several time points in the study and the second part, xALT vaccine, is a single infusion of tumor-specific T cells delivered through one of two peripheral IV catheters that are placed prior to infusion. This vaccine is investigational which means that it is not approved by the US Food and Drug Administration (FDA) and is being tested in research studies. It is hoped that by injecting the DC vaccine into your skin and infusing the T-cells into your blood, your immune system will be activated against the tumor. Once it is activated against the tumor, your immune system may recognize and attack the tumor cells in your brain and not attack normal cells. Use of a vaccine that stimulates your immune system is called immunotherapy.

Arms & Interventions

Arms

Experimental: Group A

Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine without Autologous Hematopoietic Stem cells (HSCs)

Experimental: Group B

Dose-intensified TMZ with TTRNA-DC vaccines with GM-CSF and TTRNA-xALT plus Td vaccine with Autologous Hematopoietic Stem cells (HSCs)

Interventions

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.

Drug: - Dose-intensified TMZ

After chemoradiation, subjects will receive the first cycle of dose-intensified TMZ followed by three biweekly TTRNA-DC vaccines with GM-CSF. All subjects will have an additional five cycles of dose-intensified TMZ (for a total of 6 Cycles) with concurrent monthly DC vaccinations.

Biological: - Autologous Hematopoietic Stem cells (HSCs)

Prior to chemoradiation, enrolled subjects will undergo a mobilized leukapheresis for collection of PBSCs and PBMCs for generation of DCs. One group will receive recommended dose of > 2 x 106 CD34+ HSCs/kg. Subjects enrolled in Group B will receive HSCs during TMZ Cycle 6 before receiving DC vaccine and T-cell infusion.

Biological: - TTRNA-xALT

During TMZ Cycle 6 and with DC vaccine #8, an infusion of T-cells will be administered to all subjects.

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, #6, and #8.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Children's National Hospital, Washington, District of Columbia

Status

Recruiting

Address

Children's National Hospital

Washington, District of Columbia, 20010

Site Contact

Brittany Hodik

bhodik@childrensnational.org

202-476-6493

UF Health Shands Children's Hospital, Gainesville, Florida

Status

Recruiting

Address

UF Health Shands Children's Hospital

Gainesville, Florida, 32608

Site Contact

Marcia Hodik, RN

marcia.hodik@neurosurgery.ufl.edu

352-273-6971

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