Dendritic Cell (DC) Vaccine for Malignant Glioma and Glioblastoma

NCT ID: NCT01808820

Last Updated: 2022-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-21
• Study Completion Date: 2022-07-16

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.

Conditions

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

Dendritic Cell Vaccine

Intervention Type: BIOLOGICAL

Between 1.2 to 12 million DC per dose administered once a week via intradermal injection for 4 weeks.

Tumor Lysate

Intervention Type: BIOLOGICAL

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.

Imiquimod

Intervention Type: DRUG

5% topical cream applied to vaccine site before and after administrations of DC vaccine or lysate

Leukapheresis

Intervention Type: PROCEDURE

Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained.

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).

Group Type: EXPERIMENTAL

Dendritic Cell Vaccine

Intervention Type: BIOLOGICAL

Between 1.2 to 12 million DC per dose administered once a week via intradermal injection for 4 weeks.

Tumor Lysate

Intervention Type: BIOLOGICAL

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.

Imiquimod

Intervention Type: DRUG

5% topical cream applied to vaccine site before and after administrations of DC vaccine or lysate

Leukapheresis

Intervention Type: PROCEDURE

Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained.

Interventions

Dendritic Cell Vaccine

Between 1.2 to 12 million DC per dose administered once a week via intradermal injection for 4 weeks.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

Imiquimod

5% topical cream applied to vaccine site before and after administrations of DC vaccine or lysate

Intervention Type: DRUG

Leukapheresis

Baseline, post-surgery blood draw via catheter to obtain peripheral blood mononuclear cells (PBMCs) from which Dendritic cells will be obtained.

Intervention Type: PROCEDURE

Other Intervention Names

DC Vaccine; Lysate of Tumor; Lysate Boost; Aldara; Pheresis

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.

• Minimum Eligible Age: 13 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Macarena De La Fuente, MD

OTHER

Sponsor Role: lead

Responsible Party

Macarena De La Fuente, MD

Assistant Professor of Clinical

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Macarena De La Fuente, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

Other Identifiers

20120750

Identifier Type: -

Identifier Source: org_study_id