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Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas (ACTION)

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ClinicalTrials.gov Identifier: NCT03334305
Recruitment Status : Recruiting
First Posted : November 7, 2017
Last Update Posted : December 28, 2018
Sponsor:
Collaborators:
National Pediatric Cancer Foundation
National Cancer Institute (NCI)
Moffitt Clinical Research Network (MCRN)
National Institutes of Health (NIH)
Information provided by (Responsible Party):
University of Florida

Tracking Information
First Submitted Date  ICMJE October 26, 2017
First Posted Date  ICMJE November 7, 2017
Last Update Posted Date December 28, 2018
Actual Study Start Date  ICMJE May 16, 2018
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
Evaluate safety of TTRNA-DCs and TTRNA-xALT [ Time Frame: From first DC Vaccine through 30 days after administration of the last dose of trial drug or subject death ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03334305 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 2, 2017)
  • Determine feasibility of completing treatment [ Time Frame: Up to 10 months ]
    Number of subjects completing treatment
  • Anti-tumor immune responses [ Time Frame: up to 10 months ]
    Estimate the mean difference and the variation in INF gamma secretion
  • Progression-free survival (PFS) [ Time Frame: Up to 8 years ]
    Days of PFS
  • Overall survival (OS) [ Time Frame: Up to 8 years ]
    Days of OS
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Adoptive Cellular Therapy in Pediatric Patients With High-grade Gliomas
Official Title  ICMJE ACTION Trial: Adoptive Cellular Therapy Following Dose-Intensified Temozolomide in Newly-diagnosed Pediatric High-grade Gliomas (Phase I).
Brief Summary

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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Glioma
Intervention  ICMJE
  • 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.
Study 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)
    Interventions:
    • Biological: TTRNA-DC vaccines with GM-CSF
    • Drug: Dose-intensified TMZ
    • Biological: TTRNA-xALT
    • Drug: Td vaccine
  • 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
    • Drug: Dose-intensified TMZ
    • Biological: Autologous Hematopoietic Stem cells (HSCs)
    • Biological: TTRNA-xALT
    • Drug: Td vaccine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 11, 2018)
8
Original Estimated Enrollment  ICMJE
 (submitted: November 2, 2017)
18
Estimated Study Completion Date May 2026
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender
Sexes Eligible for Study: All
Ages 3 Years to 21 Years   (Child, Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE
Contact: Marcia Hodik, RN 352-273-6971 marcia.hodik@neurosurgery.ufl.edu
Contact: Jennifer King, RN 352-273-8374 jennifer.king@neurosurgery.ufl.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03334305
Other Study ID Numbers  ICMJE IRB201701867-N
R01CA195563 ( U.S. NIH Grant/Contract )
OCR15852 ( Other Identifier: Universiy of Florida )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party University of Florida
Study Sponsor  ICMJE University of Florida
Collaborators  ICMJE
  • National Pediatric Cancer Foundation
  • National Cancer Institute (NCI)
  • Moffitt Clinical Research Network (MCRN)
  • National Institutes of Health (NIH)
Investigators  ICMJE
Principal Investigator: Elias Sayour, MD, PhD University of Florida
Study Chair: Duane Mitchell, MD, PhD University of Florida
PRS Account University of Florida
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP