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

NCT01902771 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: 20130136
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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

Keywords

Dendritic Cell Vaccine; DCV; Pediatric; Brain Tumor; In Situ; Lysate; Tumor Lysate; Glioblastoma Multiforme; GBM; Pheresis; Leukapheresis; High Grade Glioma; HGG

Outcome Measures

Primary Outcomes (2)

• Rate of Toxicity in Study Participants Receiving Protocol Therapy

  Rate of treatment-limiting toxicities (TLT) and/or adverse events in study participants receiving protocol therapy.

  Up to 28 Weeks

• Rate of Feasibility of Protocol Therapy in Study Participants

  Rate of feasibility of protocol therapy in study participants. Feasibility refers to clinical feasibility - whether or not the patient can have enough monocytes removed to manufacture Dendritic Cells.

  Up to 4 Weeks

Secondary Outcomes (5)

• Rate of Prolonged Survival or Prolonged Progression-Free Survival in Study Participants

  Up to 24 Months

• Rate of Measurable Immune Response in Subjects Receiving Protocol Therapy.

  Up to 24 months

• Comparison of clinical parameters of study participants versus associated outcomes for patients on other DC/Imiquimod studies.

  Up to 24 Months

• Estimation of the Proportion of Subjects with Recurrent Pediatric Brian Tumors who are able to complete DC Vaccine therapy and DC Vaccine + Lysate Therapy.

  Up to 24 months

• Identification of Parameters Associated with Poorer Activity of the Vaccine in Study Participants

  Up to 24 Months

Study Arms (1)

DC Vaccine + Lysate

EXPERIMENTAL

* 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.

Biological: Dendritic Cell Vaccine; Biological: Tumor Lysate; Other: Imiquimod; Procedure: Leukapheresis

Interventions

Dendritic Cell Vaccine 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.

Also known as: DC Vaccine

DC Vaccine + Lysate

Tumor Lysate 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.

Also known as: Tumor Cell Lysate, Lysate of Tumor

DC Vaccine + Lysate

Imiquimod 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.

Also known as: Aldara

DC Vaccine + Lysate

Leukapheresis 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.

Also known as: Pheresis

DC Vaccine + Lysate

Eligibility Criteria

• Age: 1 Year - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: ≥ 1 year and ≤ 29 years
• Relapse or progression of any central nervous system tumor initially diagnosed before the age of 21 years.
• 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.
• No radiotherapy and/or chemotherapy received for at least 1 month before first DC vaccination is to be administered.
• No treatment with corticosteroids or salicylates for at least 1 week before first vaccination.
• Life expectancy ≥ 3 months
• 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.
• 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

You may not qualify if:

• Pregnancy.
• Breast feeding females.
• Any concomitant participation in other therapeutic trials.
• Virus serology positive for HIV (testing is not required in the absence of clinical suspicion).
• Documented immunodeficiency or autoimmune disease.
• Other active malignancies.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Edward Ziga: lead

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

Location

MeSH Terms

Conditions

Glioma; Brain Neoplasms; Glioblastoma

Interventions

lentiviral minigene vaccine of COVID-19 coronavirus; Imiquimod; Leukapheresis; Blood Component Removal

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytapheresis; Biological Therapy; Therapeutics; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Edward Ziga, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Pediatrics

Study Record Dates

• First Submitted: July 16, 2013
• First Posted: July 18, 2013
• Study Start: September 3, 2013
• Primary Completion: October 24, 2016
• Study Completion: January 26, 2017
• Last Updated: March 10, 2017

Record last verified: 2017-03

Locations

US (1)