Dendritic Cell (DC) Vaccine for Malignant Glioma and Glioblastoma

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

The purpose of this research study is to evaluate an investigational vaccine using patent-derived dendritic cells (DC) to treat malignant glioma or glioblastoma.

Study Overview

• Status: Completed
• Conditions: Glioblastoma Multiforme; High Grade Glioma; Malignant Glioma; Anaplastic Astrocytoma
• Intervention / Treatment: Biological: Tumor Lysate; Procedure: Leukapheresis; Biological: Dendritic Cell Vaccine; Drug: Imiquimod

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	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; Procedure: Leukapheresis; Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained.; Other Names: Pheresis; Biological: Dendritic Cell Vaccine; Between 1.2 to 12 million DC per dose administered once a week via intradermal injection for 4 weeks.; Other Names: DC Vaccine; Drug: Imiquimod; 5% topical cream applied to vaccine site before and after administrations of DC vaccine or lysate; Other Names: Aldara
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).	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; Procedure: Leukapheresis; Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained.; Other Names: Pheresis; Biological: Dendritic Cell Vaccine; Between 1.2 to 12 million DC per dose administered once a week via intradermal injection for 4 weeks.; Other Names: DC Vaccine; Drug: Imiquimod; 5% topical cream applied to vaccine site before and after administrations of DC vaccine or lysate; Other Names: Aldara

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Treatment-Related Adverse Events	Adverse Events will be evaluated using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.0 by treating physician	Up to Week 32 (30 days after last dose of protocol therapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Overall Survival (OS) in Study Participants	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.	Up to Week 80 (5 years post therapy)
Rate of Progression-Free Survival (PFS) in Study Participants	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.	Up to Week 80 (5 years post therapy)
Change in MDSC Levels	Immune response will be reported as the change in Myeloid Derived Suppressor Cell (MDSC) levels from blood samples	Baseline, Up to Week 28
Change in blood counts	Measurement of immune response will be reported as the change in red and white blood counts from blood samples evaluated in million cells/microliter	Baseline, Up to Week 28
Comparison of clinical parameters associated with outcomes in study participants to patients on other DC/Imiquimod studies.	To demonstrate if the clinical parameters associated with outcomes described for patients on other DC / imiquimod protocols hold for subjects treated on this study.	Up to 5 years Post-Therapy
Proportion of participants completing intervention.	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.	Up to Week 28

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2013
• Primary Completion (Actual): November 7, 2018
• Study Completion (Actual): July 16, 2022

Study Registration Dates

• First Submitted: March 6, 2013
• First Submitted That Met QC Criteria: March 7, 2013
• First Posted (Estimate): March 11, 2013

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 19, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Dendritic Cell Vaccine; Leukapheresis; HGG; DC Vaccine
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma; Astrocytoma; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Adjuvants, Immunologic; Interferon Inducers; Vaccines; Imiquimod
• Other Study ID Numbers: 20120750

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No