Trial Information

Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib as Adjuvant Therapy for Lung and Esophageal Cancers, Thymic Neoplasms, Thoracic Sarcomas, 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.

Primary Objectives:

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

Secondary Objectives:

- To ascertain if K562-GM cell vaccines induce immunity to CT antigens in patients with
thoracic malignancies.

- To examine if oral metronomic cyclophosphamide and celecoxib therapy diminishes the
number and percentage of T regulatory cells and diminishes activity of these cells in
patients with resected thoracic malignancies at risk of recurrence.

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.