Advertisement

Topics

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

2014-08-27 03:12:55 | BioPortfolio

Summary

Background:

- Certain types of lung, esophageal, or thymic cancers and mesotheliomas have specific antigens (protein molecules) on their surfaces. Research studies have shown that giving a vaccine that contains antigens similar to these may cause an immune response, which may keep tumors from growing. Researchers are also interested in determining whether the chemotherapy drug cyclophosphamide and the anti-inflammatory drug celecoxib may help the vaccine work better, particularly in patients with lung cancer.

Objectives:

- To evaluate the safety and effectiveness of tumor cell vaccines in combination with cyclophosphamide and celecoxib in patients with cancers involving the chest.

Eligibility:

- Individuals at least 18 years of age who have had surgery for small cell or non-small cell lung cancer, esophageal cancer, thymoma or thymic carcinoma, and malignant pleural mesothelioma.

Design:

- Following recovery from surgery, chemotherapy, or radiation, participants will have leukapheresis to collect lymphocytes (white blood cells) for testing.

- Participants will receive celecoxib and cyclophosphamide to take twice a day at home, 7 days before the vaccine.

- Participants will have the vaccine in the clinical center (one or two shots per month for 6 months), and will stay in the clinic for about 4 hours after the vaccine. Participants will keep a diary at home of any side effects from the vaccine, and will continue to take cyclophosphamide and celecoxib.

- One month after the sixth vaccine, participants will provide another blood sample for testing, and if the tests are satisfactory will return to the clinic every 3 months for 2 additional vaccines.

- Participants will return to clinic for follow-up physical examinations, lab tests, and scans every 3 months for 2 years and then every 6 months for up to 3 years.

Description

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 resectable lung and esophageal cancers, thymic neoplasms, 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 times 7d q 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 EBV-transformed 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, and malignant pleural mesothelioma who have undergone resection of their neoplasms.

- 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 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.

Design:

- Following recovery from surgery and appropriate adjuvant chemotherapy and/or radiation, patients will be vaccinated via intradermal injection with 1.5x10(7) -2.5x10(7) 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.

Study Design

Allocation: Non-Randomized, Control: Uncontrolled, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Conditions

Lung Cancer

Intervention

Allogeneic Tumor Cell Vaccine (K562), Celecoxib, cyclophosphamide

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda
Maryland
United States
20892

Status

Recruiting

Source

National Institutes of Health Clinical Center (CC)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:12:55-0400

Clinical Trials [8638 Associated Clinical Trials listed on BioPortfolio]

Vaccination With GM-K562 Cells in Patients With Advanced Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML) After Allogeneic Hematopoetic Stem Cell Transplantation

The purpose of this research study is to determine if the GM-K562/leukemia cell vaccine can be safely given soon after allogeneic marrow or blood stem cell transplant. The GM-K562/leukemi...

Vaccine Therapy and Cyclophosphamide in Treating Patients Who Have Undergone Surgery for Liver Metastases Due to Colorectal Cancer

RATIONALE: Vaccines made from tumor cells may help the body build an effective immune response to kill tumor cells. Giving vaccine therapy together with chemotherapy may be a more effectiv...

Allogeneic Cellular Vaccine 1650-G for Non-Small Cell Lung Cancer

Rationale: Vaccines made from allogeneic tumor cells may help the body build an effective immune response to kill tumor cells. The Purpose of this study is to evaluate the effects of a lu...

Gefitinib and Celecoxib in Treating Patients With Refractory Non-Small Cell Lung Cancer

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Celecoxib may slow the growth of cancer by stopping blood flow to the tumor...

Trastuzumab, Cyclophosphamide, and an Allogeneic GM-CSF-secreting Breast Tumor Vaccine for the Treatment of HER-2/Neu-Overexpressing Metastatic Breast Cancer

This is a feasibility study to examine combination therapy with Trastuzumab (T), Cyclophosphamide (CY), and an allogeneic GM-CSF-secreting whole cell breast cancer vaccine in patients with...

PubMed Articles [23775 Associated PubMed Articles listed on BioPortfolio]

Soluble PD-1-based vaccine targeting MUC1 VNTR and survivin improves anti-tumor effect.

Soluble PD-1 (sPD1) can bind with ligands PD-L1/PD-L2 on the surface of dendritic cells (DCs). Therefore, a sPD1 vaccine fused with an immunogen can increase T cell activation against cancer. Here, we...

Vaccine-preventable disease following allogeneic haematopoietic stem cell transplant in Western Australia.

Infection is an important and frequent cause of mortality and morbidity following allogeneic haematopoietic stem cell transplantation (HSCT). This study was conducted to determine the epidemiology and...

Combination immunotherapy with IL-2 surface-modified tumor cell vaccine and PD-1 blockade against renal cell carcinoma.

Immunotherapy may be an effective way to prevent postoperative recurrence of renal cell carcinoma. Streptavidin-interleukin-2 (SA-IL-2) surface-modified tumor cell vaccine developed through our protei...

Allogeneic stem cell transplantation for patients with relapsed or refractory T-cell lymphoma: efficacy of lymphoma-directed conditioning against advanced disease.

Salvage chemotherapy induces disease remissions in patients with relapsed or refractory (r/r) T-cell lymphomas, but fails to provide lasting tumor control. We analyzed the outcome after peripheral blo...

Carbohydrate-based Adjuvants Activate Tumor-Specific Th1 and CD8 T-cell Responses and Reduce the immunosuppressive Activity of MDSCs.

Toll-like receptors (TLRs) and C-type lectin receptors (CLRs) contribute to antigen capture, uptake, presentation and activation of immune responses. We recently developed a new and lymph node (LN) ta...

Medical and Biotech [MESH] Definitions

A live vaccine containing attenuated poliovirus, types I, II, and III, grown in monkey kidney cell tissue culture, used for routine immunization of children against polio. This vaccine induces long-lasting intestinal and humoral immunity. Killed vaccine induces only humoral immunity. Oral poliovirus vaccine should not be administered to immunocompromised individuals or their household contacts. (Dorland, 28th ed)

A suspension of killed Bordetella pertussis organisms, used for immunization against pertussis (WHOOPING COUGH). It is generally used in a mixture with diphtheria and tetanus toxoids (DTP). There is an acellular pertussis vaccine prepared from the purified antigenic components of Bordetella pertussis, which causes fewer adverse reactions than whole-cell vaccine and, like the whole-cell vaccine, is generally used in a mixture with diphtheria and tetanus toxoids. (From Dorland, 28th ed)

A carcinoma discovered by Dr. Margaret R. Lewis of the Wistar Institute in 1951. This tumor originated spontaneously as a carcinoma of the lung of a C57BL mouse. The tumor does not appear to be grossly hemorrhagic and the majority of the tumor tissue is a semifirm homogeneous mass. (From Cancer Chemother Rep 2 1972 Nov;(3)1:325) It is also called 3LL and LLC and is used as a transplantable malignancy.

A vaccine consisting of DIPHTHERIA TOXOID; TETANUS TOXOID; and whole-cell PERTUSSIS VACCINE. The vaccine protects against diphtheria, tetanus, and whooping cough.

An ERYTHROLEUKEMIA cell line derived from a CHRONIC MYELOID LEUKEMIA patient in BLAST CRISIS.

More From BioPortfolio on "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"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topic

Pulmonary
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...


Searches Linking to this Trial