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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Malignant Glioma; Glioblastoma Multiforme; Anaplastic Astrocytoma; High Grade Glioma	Biological: Dendritic Cell Vaccine; Biological: Tumor Lysate; Drug: Imiquimod; Procedure: Leukapheresis	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 20 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dendritic Cell Vaccine For Malignant Glioma and Glioblastoma Multiforme in Adult and Pediatric Subjects
• Actual Study Start Date: August 21, 2013
• Actual Primary Completion Date: November 7, 2018
• Actual Study Completion Date: July 16, 2022

Arms and Interventions

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: 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
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: 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

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. 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.
2. 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.
3. 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
4. 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
5. 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.
6. 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.

Eligibility Criteria

• Ages Eligible for Study: 13 Years to 99 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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) ≥ 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.

Contacts and Locations

Locations

United States, Florida

University of Miami

Miami, Florida, United States, 33136

Sponsors and Collaborators

Macarena De La Fuente, MD

Investigators

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

More Information

• Responsible Party: Macarena De La Fuente, MD, Assistant Professor of Clinical, University of Miami
• ClinicalTrials.gov Identifier: NCT01808820
• Other Study ID Numbers: 20120750
• First Posted: March 11, 2013
• Last Update Posted: July 20, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Macarena De La Fuente, MD, University of Miami:

HGG; Dendritic Cell Vaccine; DC Vaccine; Leukapheresis

Additional relevant MeSH terms:

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