Adjuvant Allogeneic Tumor Cell Vaccine With Metronomic Oral Cyclophosphamide and Celecoxib in Patients Undergoing Resection of Sarcomas, Melanomas, Germ Cell Tumors, or Epithelial Malignancies Metastatic to Lungs, Pleura, or Mediastinum
During recent years, the cancer-testis (CT) antigens (CTA) have emerged as attractive
targets for cancer immunotherapy. Whereas malignancies of diverse histologies express a
variety of CTAs, immune responses to these antigens appear uncommon in cancer patients,
possibly due to low-level, heterogeneous antigen expression, as well as immunosuppressive
regulatory T cells. Conceivably, vaccination of cancer patients with allogeneic tumor cells
expressing high levels of multiple CTAs in combination with depletion of T regulatory cells
will induce broad immunity to these antigens. In order to examine this issue, patients with
sarcomas, melanomas, germ cell tumors, or epithelial malignancies metastatic to lungs,
pleura or mediastinum will be vaccinated with irradiated K562 erythroleukemia cells
expressing GM-CSF (K562-GM) following thoracic metastasectomy. Vaccines will be administered
in conjunction with metronomic oral cyclophosphamide (50 mg PO BID x 7d q 14d), and
celecoxib (400 mg PO BID). Serologic responses to a variety of recombinant CTAs will be
assessed before and after vaccination.
-To assess the safety of K562-GM allogeneic tumor cell vaccines in combination with oral
metronomic cyclophosphamide and celecoxib in patients undergoing thoracic metastasectomy.
- To ascertain if K562-GM cell vaccines induce immunity to CTAs in patients following
- 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 metastases who are at risk of recurrence
- Patients with histologically or cytologically proven sarcoma, melanoma, or epithelial
malignancies metastatic to lungs, pleura or mediastinum who can be rendered no clinical
evidence of active disease (NED).
- 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
- 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 times 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.
- Following recovery from thoracic metastasectomy, patients with NED or MRD will be
vaccinated via deep subcutaneous injection with 1x10(8) irradiated K562 GM-tumor cells
periodically over 6 months.
- Vaccines will be administered in conjunction with metronomic oral cyclophosphamide and
- 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
- 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
- Approximately 25 patients will be accrued to this trial.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess the safety of K562-GM allogeneic tumor cell vaccines in combination with oral metronomic cyclophosphamide and celecoxib in patients undergoing thoracic metastasectomy.
David S Schrump, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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