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

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

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.

Study Overview

• Status: Completed
• Conditions: Brain Tumors
• Intervention / Treatment: Drug: DC/AAT; Drug: DC/AAT-Flu; Drug: DC/KLH

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • Rockefeller University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Screening to determine eligibility (with the exception of HLA haplotyping) will be completed within 45 days fo study entry.

1. 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.

2. Prior/Concurrent Therapy

   1. Recovered from toxicity of any prior therapy

   2. 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)

   3. 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

   4. Endocrine evaluation/therapy:

      • steroid dose no greater than 1mg daily dexamethasone (or equivalent)

   5. Radiotherapy:

      • No concurrent brain radiation

   6. Surgery:

      • Surgical resection must have been completed independently of this study, and suitable samples obtained for vaccine production

3. Patient Characteristics

   1. Age: 18 and over, able to give written informed consent. May be obtained through use of legal representation such as a health care proxy
   2. Performance status: Karnofsky 60-100%
   3. Life expectancy: at least 4-6 months

   4. 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
   5. Hepatic: bilirubin less than 2mg/dL OR SGOT less than 2x ULN
   6. Renal: Creatinine no greater than 2mg/dL

   7. Cardiovascular:

      • No NYHA class III/IV status
      • No active angina, uncontrolled clinically significant cardiac arrythmia, recent (6 months) myocardial infarction
   8. Pulmonary: No symptomatic pulmonary disease or pulse oximetry less than 93% on room air
   9. Endocrine: No history of autoimmune thyroid disease
   10. Radiographic: baseline contrast-enhanced MRI or CT scan of brain post surgical resection
   11. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: DC/AAT vaccine; 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; Autologous dendritic cells that have been co-cultured with autologous apoptotic tumor (AAT) specimens.; Other Names: Dendritic cell/autologous apoptotic tumor; Drug: DC/AAT-Flu; Intradermal injection of Autologous dendritic cell vaccine (DC/AAT-Flu) after co-culture with flu-infected AAT; Other Names: dendritic cell/flu-infected autologous apoptotic tumor; Drug: DC/KLH; Intradermal injection of Autologous dendritic cell vaccine (DC/KLH) which have been co-cultured with Keyhole pimpit hemocyanin (KLH) as a positive control.; Other Names: dendritic cell/Keyhole Limplet hemocyanin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Rockefeller University
• Collaborators: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Robert Darnell, MD, PhD, Rockefeller University

Publications and helpful links

General Publications

• Frank MO, Kaufman J, Parveen S, Blachere NE, Orange DE, Darnell RB. Dendritic cell vaccines containing lymphocytes produce improved immunogenicity in patients with cancer. J Transl Med. 2014 Dec 5;12:338. doi: 10.1186/s12967-014-0338-3.

Study record dates

Study Major Dates

• Study Start: June 1, 2007
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: December 5, 2008
• First Submitted That Met QC Criteria: May 5, 2009
• First Posted (Estimate): May 6, 2009

Study Record Updates

• Last Update Posted (Estimate): December 23, 2014
• Last Update Submitted That Met QC Criteria: December 19, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: RDA-0611