Pilot Study of Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Lung and Esophageal Cancers, Thymic Neoplasms, and Malignant Pleural Mesotheliomas

Background:

During recent years, the cancer-testis (CT) antigens have emerged as attractive targets for cancer immunotherapy. Whereas lung and esophageal cancers, as well as malignant pleural mesotheliomas express a variety of CT antigens, immune responses to these antigens appear uncommon in patients with these malignancies, possibly due to low-level, heterogeneous antigen expression, as well as immunosuppressive regulatory T cells. Our published studies indicate that numerous CT antigens can be induced in tumor cells by DNA demethylating agents and histone deacetylase (HDAC) inhibitors. Conceivably, vaccination of cancer patients with allogeneic tumor cells expressing high levels of multiple CT antigens in combination with depletion of T regulatory cells will induce broad immunity to these antigens. In order to examine this issue, patients with lung and esophageal cancers, thymic neoplasms, primary thoracic sarcomas, and malignant pleural mesotheliomas will be vaccinated with irradiated K562 erythroleukemia cells expressing GM-CSF (K562-GM) following completion of appropriate combined modality therapy. Vaccines will be administered in conjunction with metronomic oral cyclophosphamide (50 mg PO BID x 7dq 14d), and celecoxib (400 mg PO BID). Serologic responses to a variety of recombinant CT antigens as well as cell-mediated recognition of autologous tumor cells and EBVtransformed B cells will be assessed before and after vaccination.

Objective:

-To assess the safety of K562-GM allogeneic tumor cell vaccines in combination with oral metronomic cyclophosphamide and celecoxib in thoracic oncology patients.

Eligibility:

• Patients with histologically or cytologically proven small cell or non-small cell lung cancer, esophageal cancer, thymoma or thymic carcinoma, primary thoracic sarcomas, and malignant pleural mesothelioma with no evidence of disease (NED) or minimal residual disease (MRD) in the primary site following standard multimodality therapy.
• Patients must be 18 years or older with an ECOG performance status of 0 - 2, without evidence of unstable or decompensated myocardial disease. Patients must have adequate pulmonary reserve evidenced by FEV1 and DLCO equal to or greater than 30% predicted; pCO2 less than 50 mm Hg and pO2 greater than 60 mm Hg on room air ABG; and be on no immunosuppressive medications except inhaled corticosteroids at the time vaccination commences.
• Patients must have a platelet count greater than 100,000, an ANC equal to or greater than 1500 without transfusion or cytokine support, a normal PT, and adequate hepatic function as evidenced by a total bilirubin of <1.5 x upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2) at the time vaccination commences.

Design:

• Following recovery from standard combined modality therapy, patients with no evidence of disease or minimal residual disease will be vaccinated via subcutaneous intradermal injection with 1x10(8) irradiated K562-GM-tumor cells periodically over 6 months. Sterility, potency and identity of the vaccines preps will be confirmed before administration.
• Vaccines will be administered in conjunction with metronomic oral cyclophosphamide and celecoxib.
• Systemic toxicities, and immunologic response to therapy will be recorded. Pre and post vaccination serologic responses to a standard panel of CT antigens as well as cell mediated responses to epigenetically-modified autologous EBV-transformed B and autologous tumor cells (if available) will be assessed before and after vaccination.
• Numbers/percentages and function of T regulatory cells in peripheral blood will be assessed before, during, and after vaccinations.
• Patients will be followed in the clinic with routine staging scans until disease recurrence.
• As the exact set of comparisons and analyses to be performed will be determined following completion of the trial, and will be based on limited numbers of patients, the analyses will be considered exploratory and hypothesis generating rather than definitive.
• Approximately 25 patients will be accrued to this trial.