Dendritic Cell Vaccine Therapy With In Situ Maturation in Pediatric Brain Tumors

NCT ID: NCT01902771

Last Updated: 2017-03-10

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-03
• Study Completion Date: 2017-01-26

Brief Summary

DC 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 children with refractory brain tumors. This will result in anti-tumor immunity that will prolong survival of subjects treated and results will be consistent with the outcomes found for subjects treated by HGG Immuno Group investigators. Study treatment will correlate with laboratory evidence of immune activation. Correlative studies will also reveal targets in the immune system which can be exploited to improve response for patients on successor trials.

Conditions

Glioma; Brain Cancer; Brain Tumor; Glioblastoma Multiforme; High Grade Glioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

DC Vaccine + Lysate

• Leukapheresis: Baseline, post-surgery;
• Dendritic Cell Vaccine (DC Vaccine): Post-Leukapheresis, administered intradermally once weekly via intradermal injection, for 4 weeks for a total of four vaccinations;
• Tumor Lysate (Lysate): Post-DC Vaccine therapy. Administered intradermally during weeks 8, 12, 16, and 28;
• Imiquimod: Self-applied topically by subject before and after scheduled DC Vaccine or Lysate administrations.

Group Type: EXPERIMENTAL

Dendritic Cell Vaccine

Intervention Type: BIOLOGICAL

Post-Leukapheresis. Subjects will receive DC Vaccine administered once weekly, via intradermal injection, for 4 weeks for a total of four vaccinations, per study protocol.

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: OTHER

Subjects will self-apply Imiquimod topically to each designated vaccine site before and after scheduled administrations of DC Vaccine or Lysate, per study protocol.

Leukapheresis

Intervention Type: PROCEDURE

Baseline, post-surgery. Subjects will undergo leukapheresis procedure during baseline, after recovery from surgery to collect peripheral blood mononuclear cells (PBMCs) from which dendritic cells will be obtained, per study protocol.

Interventions

Dendritic Cell Vaccine

Post-Leukapheresis. Subjects will receive DC Vaccine administered once weekly, via intradermal injection, for 4 weeks for a total of four vaccinations, per study protocol.

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

Subjects will self-apply Imiquimod topically to each designated vaccine site before and after scheduled administrations of DC Vaccine or Lysate, per study protocol.

Intervention Type: OTHER

Leukapheresis

Baseline, post-surgery. Subjects will undergo leukapheresis procedure during baseline, after recovery from surgery to collect peripheral blood mononuclear cells (PBMCs) from which dendritic cells will be obtained, per study protocol.

Intervention Type: PROCEDURE

Other Intervention Names

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

Eligibility Criteria

Inclusion Criteria

1. Age: ≥ 1 year and ≤ 29 years

2. Relapse or progression of any central nervous system tumor initially diagnosed before the age of 21 years.

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 or 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.

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) ≥750/L
• Lymphocytes ≥ 500/L
• Platelets ≥ 75,000/L
• Hemoglobin ≥ 9 g/dL
• Aspartate aminotransferase (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 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. Other active malignancies.

7. 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.

8. 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.

9. 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: 1 Year
• Maximum Eligible Age: 29 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Edward Ziga

OTHER

Sponsor Role: lead

Responsible Party

Edward Ziga

Assistant Professor of Clinical Pediatrics

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Edward Ziga, MD

Role: PRINCIPAL_INVESTIGATOR

University of Miami

Locations

University of Miami

Miami, Florida, United States

Countries

United States

Other Identifiers

20130136

Identifier Type: -

Identifier Source: org_study_id