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Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by University of Miami
Information provided by (Responsible Party):
Edward Ziga, University of Miami Identifier:
First received: July 16, 2013
Last updated: August 26, 2016
Last verified: August 2016
DC vaccine manufactured and partially matured using our standard operating procedures, developed in collaboration with the HGG Immuno Group, then administered through imiquimod treated skin will be safe and feasible in children with refractory brain tumors. This will result in anti-tumor immunity that will prolong survival of subjects treated and results will be consistent with the outcomes found for subjects treated by HGG Immuno Group investigators. Study treatment will correlate with laboratory evidence of immune activation. Correlative studies will also reveal targets in the immune system which can be exploited to improve response for patients on successor trials.

Condition Intervention Phase
Brain Cancer
Brain Tumor
Glioblastoma Multiforme
High Grade Glioma
Biological: Dendritic Cell Vaccine
Biological: Tumor Lysate
Other: Imiquimod
Procedure: Punch Biopsy of the Skin
Procedure: Leukapheresis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Dendritic Cell Vaccine Therapy With In Situ Maturation for Pediatric Brain Tumors

Resource links provided by NLM:

Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Number of Subjects Experiencing Adverse Events [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    To demonstrate that dendritic cell vaccine loaded with tumor lysate is feasible and safe in patients diagnosed with brain cancer as children.

Secondary Outcome Measures:
  • Number of Subjects Experiencing Complete Response or Partial Response according to RECIST Criteria 1.1 [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To demonstrate that treatment with dendritic cell vaccines loaded with tumor lysate created and matured through the in vivo process cause benefit for subjects in the form of prolonged survival or prolonged progression free survival.

  • Measurement levels of Myeloid Derived Suppressor Cells before and after treatment [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To demonstrate that treatment with dendritic cell vaccines loaded with tumor lysate injected through imiquimod treated skin cause immune responses that can be measured in subjects.

  • Number of Patients with Recurrent Brian Tumor who complete Therapy [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    To estimate the proportion of patients with recurrent pediatric brain tumors who are able to receive all administrations of DC and the proportion who are able to receive all administrations of DC and lysate.

Estimated Enrollment: 20
Study Start Date: July 2013
Estimated Primary Completion Date: July 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: DC Vaccine + Lysate Biological: Dendritic Cell Vaccine
Subjects will begin to receive DC vaccination alone, when recovered from pheresis and continue weekly for a total of four vaccinations. The vaccination with loaded DC will be given in the clinic as an intradermal injection in the upper arms. DC will be delivered with each vaccination in 6 separate syringes (3 syringe injections per arm within the area of approximately the size of a silver dollar spaced approximately equally) alternating between anterior and posterior deltoid. For subjects who are missing limbs (e.g., arms), the injection sites will be rotated between the arms and thighs (alternating anterior and lateral thigh) with anterior and posterior deltoid. For subjects who do not have an accessible deltoid, both legs will be used. All injections with DC or lysate will be done after topical treatment with imiquimod to the site of injection the day prior to injection, which will then be applied for two nights after the injection to the sites.
Other Name: DC Vaccine
Biological: Tumor Lysate
After completion of DC vaccination course, lysate of tumor will be administered during weeks 8, 12, 16, and 28. Lysate dose will be 1.5 mg of tumor lysate, divided into 4 equal doses. All lysate will be injected into one (1) arm intradermally in alternating arms/thigh as above within an area of approximately the size of a silver dollar spaced approximately equally. Lysate will be injected from one syringe for each administration. Clinical examination after study treatment ends will be required every three (3) months +/- 14 days
Other Names:
  • Tumor Cell Lysate
  • Lysate of Tumor
Other: Imiquimod
Subjects will self-apply imiquimod one night before and each night for two nights after the scheduled administration of DC or lysate. Investigator will instruct the subject to apply a thin layer of imiquimod on the selected area (approximately the area of a silver dollar) of both arms,or thigh. Subjects are advised to rinse the selected area with water (where imiquimod is applied) the morning after application. Subjects will be given a medication diary when supplied with imiquimod in which they will record both the time of application of the imiquimod, and the time of rinse of the imiquimod. The DC and lysate are to be injected in the clinic by the PI or his designee. Subjects will be evaluated 24 hours, and whenever possible, 48 hours after injection for administration site reactions and delayed type hypersensitivity reactions (DTH).
Other Name: Aklara
Procedure: Punch Biopsy of the Skin
This procedure is optional
Other Names:
  • Punch Biopsy
  • Skin Biopsy
Procedure: Leukapheresis
Patients enrolled in the study will undergo a leukapheresis procedure performed to collect peripheral blood mononuclear cells. Leukapheresis will be performed using a continuous flow blood cell separator (COBE Spectra, Caridian BCT, Lakewood, CO). This instrument relies on density gradient centrifugation to collect mononuclear cells from the apheresis patients. Leukapheresis is typically performed through a central venous catheter (a catheter inserted into one of the larger veins in the body) or through a peripheral intravenous catheter that may be placed the day of the procedure. An anticoagulant is added to circulate blood to prevent clotting during the procedure. In this study, leukapheresis will be performed to collect 1.5 x 10^09 mononuclear cells. Each procedure may take 3-5 hours.
Other Name: Pheresis


Ages Eligible for Study:   1 Year to 30 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age: > or equal to 1 year and < 30 years
  • Relapse or progression of any central nervous system tumor initially diagnosed before the age of 21 years.
  • Total or subtotal resection of tumor mass, confirmed by assessment by the neurosurgeon and by postoperative MRI scan within 72 hours after surgery. The post-operative assessment should demonstrate residual tumor less than or equal to 2 cm3 as judged by surgeon and on MRI the tumor should only show linear contrast enhancement at the border of the resection cavity or nodule less than 2 cm3.
  • No radiotherapy and/or chemotherapy received for at least 1 month before first DC vaccination is to be administered
  • No treatment with corticosteroids or salicylates for at least 1 week before first vaccination.
  • Life expectancy > 3 months
  • Written consent by patient or parent(s) (if patient is < 18 years) on an institutional review board (IRB)-approved informed consent form prior to any study-specific evaluation. Assent is required from children as per UM IRB guidelines.
  • Adequate organ function (to be measured at enrollment):

    • Absolute neutrophil count (ANC) >750/L
    • Lymphocytes > 500/L
    • Platelets > 75,000/L
    • Hemoglobin > 9 g/dL
    • AST/ALT < 2.5 X ULN; if liver metastases, < 5 X ULN
    • Serum Creatinine < 1.5 X ULN
    • Total Bilirubin < 3 X ULN
    • Albumin > 2 g/dL
  • Subjects must agree to use adequate method of contraception or abstinence throughout and up to 4 weeks after the study treatment completion.
  • Capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent.
  • Karnofsky score greater than or equal to 70 or ECOG status of 0 or 1.

Exclusion Criteria:

  • Pregnancy
  • Breast feeding females
  • Any concomitant participation in other therapeutic trials
  • Virus serology positive for HIV (testing is not required in the absence of clinical suspicion)
  • Documented immunodeficiency
  • Documented autoimmune disease
  • Other active malignancies
  • Refusal to use adequate contraception for fertile patients (females and males) during the study and for 30 days after the last dose of study treatment.
  • Any serious or uncontrolled medical or psychiatric condition that in the opinion of the investigator makes the patient not able to participate in the study.
  • Application of gliadel wafers within the prior 4 months or a plan to place gliadel wafers at the time of resection for tumor acquisition for study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01902771

United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Edward Ziga, MD   
Contact: Magdolna Pakocs   
Principal Investigator: Edward Ziga, MD         
Sponsors and Collaborators
Edward Ziga
Principal Investigator: Edward Ziga, MD University of Miami
  More Information

Responsible Party: Edward Ziga, Assistant Professor of Clinical Pediatrics, University of Miami Identifier: NCT01902771     History of Changes
Other Study ID Numbers: 20130136 
Study First Received: July 16, 2013
Last Updated: August 26, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Miami:
Brain Tumor
Tumor Lysate
Dendritic Cell Vaccine
In Situ
Glioblastoma Multiforme
High Grade Glioma

Additional relevant MeSH terms:
Brain Neoplasms
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antineoplastic Agents
Interferon Inducers processed this record on October 25, 2016