NCT02211027

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

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Robert Ferris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

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.

Conditions

• Head and Neck Squamous Cell Carcinoma (HNSCC)

Interventions

Type	Name	Description
BIOLOGICAL	Semi-allogenic human fibroblast (MRC-5) transfected with DNA	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.

Timeline

• Start date: 2016-09-01
• Primary completion: 2017-10-01
• Completion: 2028-12-01
• First posted: 2014-08-07
• Last updated: 2017-09-07

Locations

3 sites across 1 country: United States