Neoplasms

All Conditions

Carcinoma

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Head and Neck Neoplasms

All Drugs and Chemicals

Micronutrients

Antineoplastic Agents

Vitamins

Vaccines

Vitamin A

Retinol palmitate

Retinol

The vaccine is composed of lethally irradiated semi-allogenic human fibroblasts (MRC-5) transfected with genomic tumor DNA from the patients own tumor.

Each vaccination consists of up to 1 x 10e7 (not less than 7 x 10e6) DNA-transfected irradiated fibroblasts. Each vaccination will be administered intradermally using a 1 mL syringe and a 25 gauge needle.The first immunization will be administered at least 12 weeks after surgery or completion of adjuvant chemotherapy and/or radiotherapy.Three additional vaccines will be administered once a week for a total of four vaccines.

Patients will have vaccinations administered at 4 different sites as follows:

Site #1: Right arm Site #2: Left arm Site #3: Right thigh Site #4: Left thigh. Approximately equal numbers of transfected fibroblasts will be administered at each site.

Semi-allogenic human fibroblast (MRC-5) transfected with DNA

Robert L Ferris, MD

Hypothesis The incidence of toxicity in patients receiving the tumor DNA-transfected fibroblast vaccine will be acceptably low and the immunologic response rate sufficiently high to warrant further study of this therapy

The study of the vaccine will proceed in two stages after the method of Simon (102). In the first stage, 15 patients will be accrued and treated. If two or fewer objective immunologic responses occur, the study will be terminated. If 3 or more responses are observed, the study will proceed to the second stage, accruing an additional 22 patients. If the second stage is complete and a total of 9 or more immunologic responses are observed among the 37 patients treated, the treatment response rate for the vaccine will be considered high enough to warrant further study. Conversely, if the evaluation of the vaccine concludes at the first stage, or if 8 or fewer total immunologic responses occur after completing the second stage, the vaccine will not be considered for further study.

This is a single institution open-label phase Ib clinical trial designed to determine the safety of immunization of patients with resected Head and Neck Squamous Cell Carcinoma (HNSCC) with lethally irradiated semi-allogeneic human fibroblasts (MRC-5) transfected with DNA derived from the subject's own tumor and to measure the immune response to the autologous tumor vaccine.

Briefly, the plan is to use a two-stage trial design and to initially enroll 15 patients with Head and Neck Squamous Cell Carcinoma (HNSCC). The patients will undergo surgical resection to provide complete removal of the primary lesion with negative gross and microscopic margins. A portion of the primary tumor specimen not necessary for the pathologic diagnosis will be obtained to serve as a source of DNA for preparing the vaccine. Each DNA-based vaccine will contain 1 x 10e7 DNA-transfected human allogeneic fibroblasts. The vaccine will be lethally irradiated before it is used for immunization. It will be administered intradermally in the Outpatient Clinic for a total of four vaccinations delivered at weekly intervals.

Patients delayed-type hypersensitivity (DTH) responses will be tested but will not be an eligibility criterion. Immunologic response to the vaccine will be evaluated. If there is no evidence of toxicity, and \>3 of the 15 initial patients show immunologic response, the second stage of the study will be opened for accrual of 22 patients.

To determine patient's response to the DNA-based vaccines, the frequency of T cells reactive with recipient cells transfected with the autologous tumor DNA will be measured by ELISPOT for IFN-y and compared with the response to non-transfected fibroblasts prior to and after vaccination. All patients will be monitored for Immunologic response by assays include ELISPOT, flow cytometry for lymphocyte markers, Annexin V binding, TcR expression, caspase3 activity and serum antibodies.

Biological Vaccine: Semi-allogeneic Human Fibroblasts (MRC-5) Transfected With DNA

Active Immunization of Patients With Head and Neck Squamous Cell Carcinoma (HNSCC) Using Fibroblasts Transfected With DNA From Autologous Tumor

Immune competence and the presence/absence of immune suppression will be evaluated before and after vaccine administration and at the 6 month follow-up visit. The ability of DNA-based vaccines to reverse or diminish demonstrated effects in signaling defects, lymphocyte apoptosis or proportions of T(reg) in the peripheral circulation will be measured but will not be used as a criterion for evaluation of the immune response.

Toxicity will be monitored continuously from the first vaccination through the 6 month post follow up study visit for each subject.

Patients will have a follow-up visit at 1 week after last vaccination (day 29, off treatment), at 1 month, 3 months and 6 months after last vaccination or after removal from study or until death, whichever occurs first. After the 6 month follow-up visit, subjects will be followed for survival only (no additional clinical trial site visits). Patients removed from study for unacceptable adverse event(s) will be followed until resolution or stabilization of the adverse event.

All subjects should be enrolled within 2 years and follow up studies complete within 3 years.

Immunologic evidence of a response to the DNA-based vaccine will depend on the results of ELISPOT assays performed at five to seven time points: pre-surgery, pre-vaccine (either at the day -28 or Day 1 prior to vaccination), on day 15, on day 29, 1 month, 3 months (if clinically indicated at 1 and 3 months) and at the 6 month post treatment follow-up appointment. A significant difference in the frequency of vaccine reactive or anti-tumor-reactive T cells between pre- and post-vaccine determinations will be considered as a positive immune response to the vaccine.

Additionally, immune competence and the presence/absence of immune suppression will be evaluated before and after vaccine administration. The ability of DNA-based vaccines to reverse or diminish demonstrated effects in signaling defects, lymphocyte apoptosis or proportions of T(reg) in the peripheral circulation will be measured but will not be used as a criterion for evaluation of the immune response.

Immune Cell Therapy Inc.

Robert Ferris

Professor of Otolaryngology

Respiratory Tract (Lung and Bronchial) Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

vaccine composed of lethally irradiated semi-allogeneic human fibroblasts transfected with genomic tumor DNA from the patient's own tumor

Each vaccine consists of 1 x 10e7 DNA-transfected irradiated fibroblasts. A total of 4 weekly immunizations will be delivered to each patient. Each vaccine will be administered i.d. using a 1 mL syringe and a 25 gauge needle.

Subjects will have immunizations administered at 4 different sites for each vaccination as follows:

Site #1: Right arm Site #2: Left arm Site #3: Right thigh Site #4: Left thigh Approximately equal numbers of transfected fibroblasts will be administered at each site.

semi-allogeneic human fibroblasts (MRC-5) transfected with DNA

Mark A Socinski, MD

The study of the vaccine will proceed in two stages after the method of Simon (102). In the first stage, 15 patients will be accrued and treated. If two or fewer objective immunologic responses occur, the study will be terminated. If 3 or more responses are observed, the study will proceed to the second stage, accruing an additional 22 patients. If the second stage is complete and a total of 9 or more immunologic responses are observed among the 37 patients treated, the treatment response rate for the vaccine will be considered high enough to warrant further study. Conversely, if the evaluation of the vaccine concludes at the first stage, or if 8 or fewer total immunologic responses occur after completing the second stage, the vaccine will not be considered for further study.

This is an uncontrolled, non-randomized trial to evaluate safety, immunogenicity and feasibility of a new vaccine, consisting of semi-allogeneic fibroblasts transfected with autologous tumor-derived DNA. Briefly, the plan is to use a two-stage trial design and to initially enroll 15 patients with non small cell lung cancer (NSCLC) over a period of 2 years. The patients will undergo surgery and a portion of the primary tumor specimen not necessary for the pathologic diagnosis will be obtained to serve as a source of tumor DNA. Each DNA-based vaccine will contain 1 x 10e7 DNA-transfected human allogeneic fibroblasts. The vaccine will be lethally irradiated before it is used for immunization. It will be administered intradermally in the Outpatient Clinic. Patients delayed-type hypersensitivity (DTH) responses will be tested but will not be an eligibility criterion. Immunologic response to the vaccine will be evaluated. If there is no evidence of toxicity, and \>3 of the 15 initial patients show immunologic response, the second stage of the study will be opened for accrual of 22 patients. All patients will be monitored by IFN-g secretion in ELISPOT assays prior to and after vaccination for the frequency of T-cells responsive to autologous tumor (if available) and/or to the vaccine. The patients will also be evaluated before and after vaccination for the capability of their T cells to respond to activating signals delivered via the T cell receptor (TcR).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Biological Vaccine: Semi-allogeneic Human Fibroblasts (MRC-5) Transfected With DNA	NCT02211027	Head and Neck S...	Semi-allogenic ...	18 Years -	University of Pittsburgh
Immunization of Patients With Non Small Cell Lung Cancer (NSCLC)	NCT00793208	Non Small Cell ...	semi-allogeneic...	18 Years -	University of Pittsburgh

Spots Global Cancer Trial Database for autologous tumor