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

Brain Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00893945
• Other study ID #: RDA-0611
• Status: Completed
• Phase: Phase 1
• First received: December 5, 2008
• Last updated: December 19, 2014
• Start date: June 2007
• Est. completion date: December 2013

Study information

• Verified date: December 2014
• Source: Rockefeller University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Brain Neoplasms
• Brain Tumors

Intervention

Drug:
• DC/AAT
Autologous dendritic cells that have been co-cultured with autologous apoptotic tumor (AAT) specimens.
• DC/AAT-Flu
Intradermal injection of Autologous dendritic cell vaccine (DC/AAT-Flu) after co-culture with flu-infected AAT
• 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.

Locations

Country	Name	City	State
United States	Rockefeller University	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Rockefeller University	Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Toxicity- assessment of safety and tolerability		week 0 to week 9	Yes
Secondary	Measurable disease		baseline and after completion of vaccination	No
Secondary	Activity-monitoring both clinical and immunologic parameters		week 0 to week 9	No