Dendritic Cell Vaccine For Malignant Glioma and Glioblastoma Multiforme in Adult and Pediatric Subjects

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by University of Miami
Sponsor:
Information provided by (Responsible Party):
John Goldberg, University of Miami
ClinicalTrials.gov Identifier:
NCT01808820
First received: March 6, 2013
Last updated: July 24, 2014
Last verified: July 2014
  Purpose

Dendritic Cell 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 patients with high grade glioma. This will result in anti-tumor immunity that will prolong survival of subjects treated. Study treatment will correlate with laboratory evidence of immune activation.


Condition Intervention Phase
Malignant Glioma
Glioblastoma Multiforme
Anaplastic Astrocytoma
High Grade Glioma
Biological: Dendritic Cell Vaccine
Biological: Tumor Lysate
Other: Imiquimod
Procedure: Leukapheresis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Dendritic Cell Vaccine For Malignant Glioma and Glioblastoma Multiforme in Adult and Pediatric Subjects

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: 5 years ] [ Designated as safety issue: Yes ]
    To demonstrate that dendritic cell vaccine loaded with tumor lysate is feasible and safe in pediatric and adult subjects with relapsed high grade glioma or glioblastoma multiforme treated at the University of Miami. This will be done in the same manner as that of our HGG Immuno collaborators and will use imiquimod topically as the final step in maturing the vaccine product. The number of subjects experiencing adverse events will be characterized by type, grade and attribution to treatment as well as by time of onset in relation to the day of Dendritic Cell vaccination. We will report the number and percent of unacceptable adverse events among subjects


Secondary Outcome Measures:
  • Measurement levels of Myeloid Derived Supressor Cells before and after treatment [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To demonstrate that treatment with dendritic cell vaccines loaded with tumor lysate created injected through imiquimod treated skin cause immune responses that can be measured in subjects

  • Overall Survival [ Time Frame: 5 years ] [ 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. Measured from the date of enrollment on study to the recorded date of death

  • Progression-Free Survival [ Time Frame: 5 years ] [ 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 progression free survival. Measured from the date of enrollment on study to the earliest occurrence of progression, relapse or death from any cause

  • Number of subjects achieving complete response or partial response according to RECIST Criteria v. 1.1 [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    To demonstrate if the clinical parameters associated with outcomes described for patients on other DC / imiquimod protocols hold for subjects treated on our study.

  • Number of subjects with recurrent glioma who are able to receive all administrations of the Dendritic Cell Vaccine [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Number of subjects with recurrent glioma who are able to receive all adminstrations 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: Dendritic Cell Vaccine Biological: Dendritic Cell Vaccine
Subjects will begin to receive DC vaccination alone, approximately 2 weeks after 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 up to 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 Name: 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.
Other Name: Aldara
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 2 x 10^10 mononuclear cells. Each procedure may take 3-5 hours.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age: >= 13 years and < 100 years
  • Relapse of high grade glioma (anaplastic astrocytoma WHO grade III or glioblastoma multiforme WHO grade IV), histologically proven at first stage of disease (radiological evidence for recurrence suffices)
  • Relapse of glioma, which was grade II at initial diagnosis, but which is grade III or IV at relapse based on radiological or pathological criteria
  • 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. Corticosteriod therapy should be rapidly weaned within 1-2 weeks after surgery
  • 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
  • ECOG performance status of 0 or 1
  • 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 above 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
  • Mandatory treatment with corticosteroids or salicylates prior to first vaccination
  • 3.3.8 Other active malignancies
  • Patients with unresectable tumors, for instance pontine gliomas, are excluded.
  • 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.
  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 ClinicalTrials.gov identifier: NCT01808820

Locations
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: John Goldberg, MD    305-243-2795    jgoldberg2@med.miami.edu   
Contact: Emil Kamar       e.kamar@med.miami.edu   
Principal Investigator: John Goldberg, MD         
Sub-Investigator: Ricardo Komotar, MD         
Sub-Investigator: Ofelia Alvarez, MD         
Sub-Investigator: Martin Andreasky, MD, PhD         
Sub-Investigator: Antonello Podda, MD         
Sub-Investigator: Julio Barredo, MD         
Sub-Investigator: Joanna Davis, MD         
Sub-Investigator: Cristina Fernandes, MD         
Sub-Investigator: Roberto Heros, MD         
Sub-Investigator: Deborah Heros, MD         
Sub-Investigator: Ronald Benveniste, MD         
Sub-Investigator: Lynn Feun, MD         
Sponsors and Collaborators
University of Miami
Investigators
Principal Investigator: John Goldberg, MD University of Miami
  More Information

No publications provided

Responsible Party: John Goldberg, Assistant Professor of Clinical, University of Miami
ClinicalTrials.gov Identifier: NCT01808820     History of Changes
Other Study ID Numbers: 20120750
Study First Received: March 6, 2013
Last Updated: July 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
Malignant Glioma
Glioblastoma Multiforme
Anaplastic Astrocytoma
High Grade Glioma
HGG
Dendritic Cell Vaccine
DC Vaccine
Leukapheresis

Additional relevant MeSH terms:
Glioma
Astrocytoma
Glioblastoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Imiquimod
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Interferon Inducers

ClinicalTrials.gov processed this record on August 21, 2014