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Dendritic Cell (DC) Vaccine for Malignant Glioma and Glioblastoma

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ClinicalTrials.gov Identifier: NCT01808820
Recruitment Status : Active, not recruiting
First Posted : March 11, 2013
Last Update Posted : February 6, 2019
Sponsor:
Information provided by (Responsible Party):
Macarena De La Fuente, University of Miami

Tracking Information
First Submitted Date  ICMJE March 6, 2013
First Posted Date  ICMJE March 11, 2013
Last Update Posted Date February 6, 2019
Actual Study Start Date  ICMJE August 21, 2013
Actual Primary Completion Date November 2, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 28, 2016)
Number of Study Participants Experiencing Adverse Events [ Time Frame: Up to 30 days after Last Dose of Protocol Therapy ]
The number of study participants experiencing adverse events.
Original Primary Outcome Measures  ICMJE
 (submitted: March 7, 2013)
Number of Subjects Experiencing Adverse Events [ Time Frame: 5 years ]
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
Change History Complete list of historical versions of study NCT01808820 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 28, 2016)
  • Rate of Overall Survival (OS) in Study Participants [ Time Frame: Up to 5 years Post-Therapy ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 7, 2013)
  • Measurement levels of Myeloid Derived Supressor Cells before and after treatment [ Time Frame: 5 years ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dendritic Cell (DC) Vaccine for Malignant Glioma and Glioblastoma
Official Title  ICMJE Dendritic Cell Vaccine For Malignant Glioma and Glioblastoma Multiforme in Adult and Pediatric Subjects
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Malignant Glioma
  • Glioblastoma Multiforme
  • Anaplastic Astrocytoma
  • High Grade Glioma
Intervention  ICMJE
  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Biological: Dendritic Cell Vaccine
    • Biological: Tumor Lysate
    • Other: Imiquimod
    • Procedure: Leukapheresis
  • 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.
    Interventions:
    • Biological: Dendritic Cell Vaccine
    • Biological: Tumor Lysate
    • Other: Imiquimod
    • Procedure: Leukapheresis
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 Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 7, 2013)
20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE November 2023
Actual Primary Completion Date November 2, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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) ≥ 0.75 10*3/µl
    • Lymphocytes ≥ 0.5 10*3/µl
    • Platelets ≥ 75 10*3/µl
    • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 13 Years to 99 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01808820
Other Study ID Numbers  ICMJE 20120750
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  ICMJE Not Provided
Responsible Party Macarena De La Fuente, University of Miami
Study Sponsor  ICMJE Macarena De La Fuente
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Macarena De La Fuente, MD University of Miami
PRS Account University of Miami
Verification Date February 2019

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