Dendritic Cell (DC) Vaccine for Malignant Glioma and Glioblastoma

• ClinicalTrials.gov Identifier: NCT01808820
• Recruitment Status: Completed
• First Posted: March 11, 2013
• Last Update Posted: July 20, 2022
• Sponsor: Macarena De La Fuente, MD
• Information provided by (Responsible Party): Macarena De La Fuente, MD, University of Miami

Tracking Information

• First Submitted Date: March 6, 2013
• First Posted Date: March 11, 2013
• Last Update Posted Date: July 20, 2022
• Actual Study Start Date: August 21, 2013
• Actual Primary Completion Date: November 7, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 11, 2021)

Number of Participants with Treatment-Related Adverse Events [ Time Frame: Up to Week 32 (30 days after last dose of protocol therapy) ]

Adverse Events will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 by treating physician

Original Primary Outcome Measures (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

Current Secondary Outcome Measures (submitted: January 11, 2021)

• Rate of Overall Survival (OS) in Study Participants [ Time Frame: Up to Week 80 (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: Up to Week 80 (5 years post therapy) ]
  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.
• Change in MDSC Levels [ Time Frame: Baseline, Up to Week 28 ]
  Immune response will be reported as the change in Myeloid Derived Suppressor Cell (MDSC) levels from blood samples
• Change in blood counts [ Time Frame: Baseline, Up to Week 28 ]
  Measurement of immune response will be reported as the change in red and white blood counts from blood samples evaluated in million cells/microliter
• 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 participants completing intervention. [ Time Frame: Up to Week 28 ]
  Proportion of participants able to receive all administrations of DC vaccine and those who are able to receive all administration of DC vaccine and lysate will be reported.

Original Secondary Outcome Measures (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: Dendritic Cell (DC) Vaccine for Malignant Glioma and Glioblastoma
• Official Title: Dendritic Cell Vaccine For Malignant Glioma and Glioblastoma Multiforme in Adult and Pediatric Subjects
• Brief Summary: The purpose of this research study is to evaluate an investigational vaccine using patent-derived dendritic cells (DC) to treat malignant glioma or glioblastoma.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Malignant Glioma
• Glioblastoma Multiforme
• Anaplastic Astrocytoma
• High Grade Glioma

Intervention

• Biological: Dendritic Cell Vaccine
  Between 1.2 to 12 million DC per dose administered once a week via intradermal injection for 4 weeks.
  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
• Drug: Imiquimod
  5% topical cream applied to vaccine site before and after administrations of DC vaccine or lysate
  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

• Experimental: Safety Pilot: DC Vaccine/Lysate
  Participants in this group will undergo leukapheresis after standard of care surgical tumor resection. Leukapheresis will be used to obtain peripheral blood mononuclear cells (PBMC) from which the dendritic cells (DC) will be obtained. Retrieved DC will be used as a vaccine once weekly on Weeks 1-4 within 3 weeks from end of leukapheresis. Participants will also receive Imiquimod, which will be applied one evening prior to DC dose for 8 hours then for 8 hours each of the next two evenings. Enrollment of participants in the Pilot group will be staggered until the second participant has no treatment limiting toxicities. For the first five subjects to be enrolled in the pilot, the administration of DC to each subject will be delayed until the prior subject has received the second administration of DC. Participants will also receive Lysate of tumor administered every 4 weeks + 3 days on Weeks 8, 12, 16 and 28 (+ / - 3 days).
  Interventions:

  • Biological: Dendritic Cell Vaccine
  • Biological: Tumor Lysate
  • Drug: Imiquimod
  • Procedure: Leukapheresis
• Experimental: Expansion Cohort: DC Vaccine/Lysate
  Participants in this group will undergo leukapheresis within after standard of care surgical tumor resection. Leukapheresis will be used to obtain peripheral blood mononuclear cells (PBMC) from which the dendritic cells (DC) will be obtained. Retrieved DC will be used as a vaccine once weekly on Weeks 1-4 within 3 weeks from end of pheresis. Participants will also receive Imiquimod, which will be applied one evening prior to DC dose for 8 hours then for 8 hours each of the next two evenings. Participants will also receive Lysate of tumor administered every 4 weeks + 3 days on Weeks 8, 12, 16 and 28 (+ / - 3 days).
  Interventions:

  • Biological: Dendritic Cell Vaccine
  • Biological: Tumor Lysate
  • Drug: Imiquimod
  • Procedure: Leukapheresis

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 7, 2013): 20
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 16, 2022
• Actual Primary Completion Date: November 7, 2018 (Final data collection date for primary outcome measure)

Eligibility 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) ≥ 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

• Sexes Eligible for Study: All

• Ages: 13 Years to 99 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01808820
• Other Study ID Numbers: 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

• Plan to Share IPD: No

• Current Responsible Party: Macarena De La Fuente, MD, University of Miami
• Original Responsible Party: University of Miami Sylvester Comprehensive Cancer Center
• Current Study Sponsor: Macarena De La Fuente, MD
• Original Study Sponsor: University of Miami Sylvester Comprehensive Cancer Center
• Collaborators: Not Provided

Investigators

• Principal Investigator: Macarena De La Fuente, MD; University of Miami

• PRS Account: University of Miami
• Verification Date: July 2022