Autologous Dendritic Cells Pulsed With Autologous Apoptotic Tumor Cells Administered to Patients With Brain Tumors

Study Overview
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Brief Summary
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This study involves cancer research and the purpose is to assess the safety and activity of a type of vaccine as immune therapy for cancer. This vaccine will be made from each participant's own immune cells (called dendritic cells) obtained by blood donation. Dendritic cells (DCs) are immune cells whose role is to identify foreign material in the body (such as bacteria, viruses, or tumor cells). When DCs recognize this material, they use it to activate other cells of the immune system to mount an attack against that foreign material. In the Laboratory of Molecular Neuro-Oncology, each participant's DCs will be loaded with samples of their own tumor cells that were obtained at surgical resection. These tumor cells are killed in the laboratory using a special protocol, and then fed to the DCs. The DCs eat this material, and these fed DCs make up the vaccine.

Detailed Description
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If you are eligible, and you decide to join this research study, you will get two to three shots of the experimental vaccine, each three weeks apart. You will then have a follow up period where we will monitor you and your medical records for any affects of the experimental treatment.

Official Title
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A Phase I Study of Autologous Dendritic Cells Pulsed With Autologous Apoptotic Tumor Cells (DC/AAT) Administered Intradermally to Cancer Patients With Brain Tumors

Conditions
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Brain Tumors

Intervention / Treatment
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* Drug: DC/AAT
* Drug: DC/AAT-Flu
* Drug: DC/KLH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Screening to determine eligibility (with the exception of HLA haplotyping) will be completed within 45 days fo study entry. Disease Characteristics Histologically confirmed brain cancers, reviewed at MSKCC. Pathologic examination will be of surgical resection specimens deemed of suitable quality for definitive diagnosis by the histopathologist. Primary Brain Tumors: Anaplastic astrocytoma Glioblastoma multiforme Anaplastic oligodendroglioma Malignant mixed oligoastrocytoma Secondary (metastatic) brain tumors - newly diagnosed or recurrent disease All histological grade of disease accepted Surgically accessible tumor for which resection is indicated. Tumors may be from initial resections or re-resections. Recovery of a minimum of 1x10^7 tumor cells ex vivo is required. Patients with primary brain tumors must have been previously treated with conventional therapy. Prior/Concurrent Therapy Recovered from toxicity of any prior therapy Biologic Therapy No concurrent other immunotherapy and no prior immunotherapy with any of the components of the current regimen (autologous DCs, cancer cells, or KLH) Chemotherapy: No concurrent immunomodulatory or chemotherapy therapy Chemotherapy, including temozolomide and local chemotherapies such as Gliadel Wafers, must be deferred until after last post-vaccine leukapheresis Endocrine evaluation/therapy: steroid dose no greater than 1mg daily dexamethasone (or equivalent) Radiotherapy: No concurrent brain radiation Surgery: Surgical resection must have been completed independently of this study, and suitable samples obtained for vaccine production Patient Characteristics Age: 18 and over, able to give written informed consent. May be obtained through use of legal representation such as a health care proxy Performance status: Karnofsky 60-100% Life expectancy: at least 4-6 months Hematopoietic: WBC greater than 3,800 Absolute lymphocytes greater than 500 Absolute neutrophil counter great than 1,500/mm^3 Platelets greater than 100,000/mm^3 Hb greater than or equal to 10g/dL Hepatic: bilirubin less than 2mg/dL OR SGOT less than 2x ULN Renal: Creatinine no greater than 2mg/dL Cardiovascular: No NYHA class III/IV status No active angina, uncontrolled clinically significant cardiac arrythmia, recent (6 months) myocardial infarction Pulmonary: No symptomatic pulmonary disease or pulse oximetry less than 93% on room air Endocrine: No history of autoimmune thyroid disease Radiographic: baseline contrast-enhanced MRI or CT scan of brain post surgical resection Coagulation: No unexplained INR >2 Exclusion criteria: No active infection requiring antibiotics No history of HIV, hepatitis B or hepatitis C virus infection, no history of high risk behavior for such infection (intravenous drug abuse, men having unprotected sex with men). Laboratory evaluation for HIV, hepatitis B, hepatitis C to be obtained prior to study entry No history of hypersensitivity to vaccine components No history of autoimmune or vasculitic disease (including but not limited to systemic lupus erythematosis, Hashimoto's thyroiditis, rheumatoid arthritis, systemic necrotizing vasculitides (polyarteritis nodosa group), hypersensitivity vasculitis, Wegener's granulomatosis), scleroderma, multiple sclerosis, juvenile-onset insulin-dependent diabetes No medical or psychiatric illness or social condition that, in the opinion of the investigator, would interfere with adherence to study requirements No alcohol or drug use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DC/AAT vaccine<br>Intradermal injection of 3 Autologous dendritic cell vaccines (DC/AAT, DC/AAT-flu, DC/KLH) that have been co-cultured with autologous apoptotic tumor specimens. | Drug: DC/AAT<br>* Autologous dendritic cells that have been co-cultured with autologous apoptotic tumor (AAT) specimens.<br>* Other names: Dendritic cell/autologous apoptotic tumor;Drug: DC/AAT-Flu<br>* Intradermal injection of Autologous dendritic cell vaccine (DC/AAT-Flu) after co-culture with flu-infected AAT<br>* Other names: dendritic cell/flu-infected autologous apoptotic tumor;Drug: DC/KLH<br>* Intradermal injection of Autologous dendritic cell vaccine (DC/KLH) which have been co-cultured with Keyhole pimpit hemocyanin (KLH) as a positive control.<br>* Other names: dendritic cell/Keyhole Limplet hemocyanin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity- assessment of safety and tolerability |  | week 0 to week 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurable disease |  | baseline and after completion of vaccination | 
| Activity-monitoring both clinical and immunologic parameters |  | week 0 to week 9 |