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Dendritic Cell (DC) Vaccine for Malignant Glioma and Glioblastoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2016 by University of Miami
Sponsor:
Information provided by (Responsible Party):
Edward Ziga, University of Miami
ClinicalTrials.gov Identifier:
NCT01808820
First received: March 6, 2013
Last updated: November 28, 2016
Last verified: November 2016
  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: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel 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 Study Participants Experiencing Adverse Events [ Time Frame: Up to 30 days after Last Dose of Protocol Therapy ] [ Designated as safety issue: Yes ]
    The number of study participants experiencing adverse events.


Secondary Outcome Measures:
  • Rate of Overall Survival (OS) in Study Participants [ Time Frame: Up to 5 years Post-Therapy ] [ Designated as safety issue: No ]
    Rate of overall survival in study participants receiving protocol therapy. Overall survival is defined as the time elapsed from the start of treatment until death. For surviving patients, follow-up will be censored at the date of last contact.

  • Rate of Progression-Free Survival (PFS) in Study Participants [ Time Frame: 6, 12 and 24 months ] [ Designated as safety issue: No ]
    Rate of prolonged progression-free survival in study participants receiving protocol therapy. Progression-Free Survival (PFS) is defined as the time elapsed from the start of treatment to the date of documented progression or death, whichever comes first. For surviving patients without progression who begin alternative treatment, PFS will be censored at the last date of documented progression-free status prior to starting alternative treatment. Similarly, losses to follow up will be censored at the last date of documented progression-free status.

  • Measurement levels of immune response before and after treatment [ Time Frame: Baseline, Up to Week 28 ] [ Designated as safety issue: No ]
    Immune response is demonstrated by Myeloid Derived Suppressor Cell (MDSC) levels and blood counts in study participants. Pre and post-treatment Myeloid Derived Suppressor Cell (MDSC) levels and blood counts will be evaluated.

  • Comparison of clinical parameters associated with outcomes in study participants to patients on other DC/Imiquimod studies. [ Time Frame: Up to 5 years Post-Therapy ] [ 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 this study.

  • Proportion of Study Participants who complete all DC Vaccine administrations and the proportion who complete all DC Vaccine and Lysate administrations. [ Time Frame: Up to 5 years Post-Therapy ] [ Designated as safety issue: No ]
    The proportion of patients with recurrent glioma 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: Safety Pilot: DC Vaccine/Lysate
  • Leukapheresis: Baseline, post-surgery;
  • Dendritic Cell Vaccine (DC Vaccine): Post-Leukapheresis, administered once weekly in dose-escalation scheme for 4 weeks;
  • Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered during weeks 8, 12, 16 and 28;
  • Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Biological: Dendritic Cell Vaccine
Subjects will receive DC Vaccine administered once weekly, via intradermal injection, for 4 weeks for a total of four vaccinations, per study protocol.
Other Name: DC Vaccine
Biological: Tumor Lysate
Post-DC Vaccine therapy. Up to 1.5 mg of Lysate of tumor per dose administered via intradermal injection at intervals defined by study protocol.
Other Names:
  • Lysate of Tumor
  • Lysate Boost
Other: Imiquimod
Subjects will self-apply Imiquimod topically to each designated vaccine site before and after scheduled administrations of DC Vaccine or Lysate, per study protocol.
Other Name: Aldara
Procedure: Leukapheresis
Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained.
Other Name: Pheresis
Experimental: Expansion Cohort: DC Vaccine/Lysate
  • Leukapheresis: Baseline, post-surgery;
  • Dendritic Cell Vaccine (DC Vaccine): Post-Leukapheresis, administered once weekly in dose-escalation scheme for 4 weeks;
  • Lysate of Tumor (Lysate): Post-DC Vaccine therapy, administered every 4 weeks for a total of 4 doses;
  • Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.
Biological: Dendritic Cell Vaccine
Subjects will receive DC Vaccine administered once weekly, via intradermal injection, for 4 weeks for a total of four vaccinations, per study protocol.
Other Name: DC Vaccine
Biological: Tumor Lysate
Post-DC Vaccine therapy. Up to 1.5 mg of Lysate of tumor per dose administered via intradermal injection at intervals defined by study protocol.
Other Names:
  • Lysate of Tumor
  • Lysate Boost
Other: Imiquimod
Subjects will self-apply Imiquimod topically to each designated vaccine site before and after scheduled administrations of DC Vaccine or Lysate, per study protocol.
Other Name: Aldara
Procedure: Leukapheresis
Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained.
Other Name: Pheresis

  Eligibility

Ages Eligible for Study:   13 Years to 99 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age: ≥ 13 years and ≤ 99 years.
  2. (2a) Relapse of high grade glioma (anaplastic astrocytoma World Health Organization (WHO) grade III or glioblastoma multiforme WHO grade IV), histologically proven at first stage of disease (radiological evidence for recurrence suffices); OR (2b) 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.
  3. 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 cm^3 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 cm^3.
  4. No radiotherapy and/or chemotherapy received for at least 1 month before first DC vaccination is to be administered
  5. No treatment with corticosteroids or salicylates for at least 1 week before first vaccination. Corticosteroid therapy should be rapidly weaned within 1-2 weeks after surgery.
  6. Life expectancy > 3 months.
  7. 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 University of Miami (UM) IRB guidelines. Subject must be capable of understanding the investigational nature, potential risks and benefits of the study and able to provide valid informed consent.
  8. 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
    • Aspartate transaminase (AST)/Alanine transaminase (ALT) ≤ 2.5 X upper limit of normal (ULN); if liver metastases, ≤ 5 X ULN
    • Serum Creatinine ≤ 1.5 X ULN
    • Total Bilirubin ≤ 3 X ULN
    • Albumin > 2 g/dL
  9. Subjects must agree to use adequate method of contraception or abstinence throughout and up to 4 weeks after the study treatment completion.
  10. Karnofsky score 70 or higher or Eastern Cooperative Oncology Group (ECOG) status of 0 or 1.

Exclusion Criteria:

  1. Pregnancy.
  2. Breast feeding females.
  3. Any concomitant participation in other therapeutic trials.
  4. Virus serology positive for HIV (testing is not required in the absence of clinical suspicion).
  5. Documented immunodeficiency or autoimmune disease.
  6. Mandatory treatment with corticosteroids or salicylates in the week prior to first vaccination.
  7. Other active malignancies.
  8. Patients with unresectable tumors, for instance pontine gliomas, are excluded.
  9. 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.
  10. 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.
  11. 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 ClinicalTrials.gov identifier: NCT01808820

Locations
United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Macarena De La Fuente, MD       mdelafuente@med.miami.edu   
Contact: Magdolna Pakocs       mps65@med.miami.edu   
Principal Investigator: Macarena De La Fuente, MD         
Sponsors and Collaborators
Edward Ziga
Investigators
Principal Investigator: Macarena De La Fuente, MD University of Miami
  More Information

Responsible Party: Edward Ziga, Assistant Professor of Clinical Pediatrics, University of Miami
ClinicalTrials.gov Identifier: NCT01808820     History of Changes
Other Study ID Numbers: 20120750 
Study First Received: March 6, 2013
Last Updated: November 28, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

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
Glioblastoma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Vaccines
Imiquimod
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Antineoplastic Agents
Interferon Inducers

ClinicalTrials.gov processed this record on December 02, 2016