Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor

NCT01171469 | Completed Phase 1 DMC

• 2 other identifiers: 2008LS0530809M48641
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center Phase I study to determine the safety and maximum tolerated dose (MTD) of autologous dendritic cells (DCs) loaded with allogeneic brain tumor stem cells administered as a vaccination in children and adults with recurrent brain tumors. Once the MTD has been determined, we will conduct a phase II study to determine efficacy. Clinical trials that utilize DCs for immunotherapy have demonstrated significant survival benefit for patients who exhibit robust immune responses against tumor cells. Unfortunately, at the present time the majority of tumor patients are unable to mount an adequate immune response and thus succumb to their tumors. We postulate that the inability to generate an appropriate immune response in these patients is due to a lack of sufficient numbers of appropriate T cells due to an inadequate source of tumor antigens.

Conditions

Brain Tumor; Glioblastoma; Medulloblastoma; Ependymoma; Anaplastic Astrocytoma

Keywords

Brain tumor; Immunotherapy; Glioma

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose

  To determine the safety and maximum tolerated dose (MTD) of dendritic cells (DCs) loaded with brain tumor stem cells (BTSCs) as a source of tumor antigen for immunotherapy in children and adults with recurrent GBM, ependymoma or medulloblastoma brain tumors. Toxicity is determined using the criteria established by the National Cancer Institute's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE).

  4 Weeks Post Vaccination

Secondary Outcomes (1)

• Time to Tumor Progression

  Every 4 Weeks From Baseline to 1 Year

Study Arms (3)

Dose Level 3

EXPERIMENTAL

15 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.

Biological: Dendritic Cells; Drug: Imiquimod

Dose Level 2

EXPERIMENTAL

10 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.

Biological: Dendritic Cells; Drug: Imiquimod

Dose Level 1

EXPERIMENTAL

5 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.

Biological: Dendritic Cells; Drug: Imiquimod

Interventions

Dendritic Cells BIOLOGICAL

5, 10 or 15 Million dendritic cells (DCs) - administered via intradermal injections in 0.5 ml Phosphate Buffered Saline (PBS) in the shoulders near the back of the neck to facilitate trafficking of the DCs to the cervical lymph nodes.

Also known as: DCs

Dose Level 1; Dose Level 2; Dose Level 3

Imiquimod DRUG

Imiquimod (INN) is a prescription medication that acts as an immune response modifier. Imiquimod is marketed as 5% Aldara cream in 250 mg packets, providing a total dose of 12.5 mg per packet and sufficient to cover 20 square centimeters. The contents of ½ of a packet will be applied as a thin film to cover approximately 10 square centimeters of skin in the area of the planned vaccination.

Also known as: Aldara

Dose Level 1; Dose Level 2; Dose Level 3

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed brain tumors (glioblastoma multiforme, anaplastic astrocytoma, medullo
• Age 0 through 17 years (pediatric subjects), and 18 years and above (adult subjects)
• Lansky score of ≥ 60 (0-15 years) or Karnofsky (16 years or older) performance score of ≥ 60%
• Adequate organ function within 14 days of study registration including the following:
• Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) ≥ 1.0 x 10\^9/L, platelets ≥100 x 10\^9/L; hemoglobin ≥ 8 g/dL
• Hepatic: bilirubin ≤1.3 mg/dL or 0-22 mmol/L, aspartate transaminase (AST) and alanine transaminase (ALT) \< 3 x upper limit of normal (ULN)
• Renal: Normal serum creatinine for age (below) or creatinine clearance \>60 ml/min/1.73 m\^2.
• Sexually active women of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of the vaccination period. Sexually active men must agree to use barrier contraceptive for the duration of the vaccination period.
• Willingness to travel to participate in study if from outside local region.
• Voluntary written informed consent must be obtained from all patients (if of assent age) and their parents or legal guardians before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

You may not qualify if:

• Pregnant or breast-feeding. Pregnancy testing will be performed on all menstruating females within 14 days of study enrollment.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.
• Currently receiving any other investigational agents.
• History of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, ongoing pregnancy, transplant immuno-suppression).
• Any conditions that could potentially alter immune function (e.g., AIDS, multiple sclerosis, diabetes, renal failure).

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Brain Neoplasms; Glioblastoma; Medulloblastoma; Ependymoma; Astrocytoma; Glioma

Interventions

Imiquimod

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Christopher Moertel, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2010
• First Posted: July 28, 2010
• Study Start: September 1, 2010
• Primary Completion: May 1, 2012
• Study Completion: June 1, 2012
• Last Updated: December 2, 2017

Record last verified: 2017-11

Locations

US (1)