Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and GM-CSF in Treating Patients With Recurrent, Refractory, or Metastatic Non-Small Cell Lung Cancer - Full Text View

Sponsors and Collaborators:	Roger Williams Medical Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00569296

Purpose

RATIONALE: Giving autologous lymphocytes that have been treated in the laboratory with antibodies may stimulate the immune system to kill tumor cells. Aldesleukin may stimulate the lymphocytes to kill tumor cells. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving laboratory-treated autologous lymphocytes together with aldesleukin and GM-CSF may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of laboratory-treated autologous lymphocytes when given together with aldesleukin and GM-CSF in treating patients with recurrent, refractory, or metastatic non-small cell lung cancer.

Condition	Intervention	Phase
Lung Cancer	Drug: EGFRBi-armed autologous activated T cells Drug: aldesleukin Drug: sargramostim	Phase I

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Aldesleukin Sargramostim Granulocyte-macrophage colony-stimulating factor Cetuximab Visilizumab

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study of Anti-CD3 x Cetuximab-Armed Activated T Cells, Low Dose IL-2, and GM-CSF for EGFR-Positive, Advanced Non-Small Cell Lung Cancer

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Safety [ Designated as safety issue: Yes ]
Maximum tolerated dose of EGFRBi-armed autologous activated T-cells [ Designated as safety issue: Yes ]
Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro [ Designated as safety issue: No ]

Secondary Outcome Measures:

Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Evaluation of tumor markers and human anti-mouse antibody responses as assessed by carcinoembryonic antigen (CEA) levels in serum samples and development of IgG and IgM anti-mouse antibody responses to the Bi-antibodies [ Designated as safety issue: No ]
Determination of immunologic changes by evaluation of peripheral blood lymphocytes [ Designated as safety issue: No ]
Determination of immunologic changes by evaluation of cytotoxic T-lymphocytes as measured by interferon gamma ELISPOTS directed at autologous tumor or lung cancer cell lines [ Designated as safety issue: Yes ]
Determination of immunologic changes by evaluation of phenotypes of peripheral blood mononuclear cells before and after immunotherapy [ Designated as safety issue: No ]

Estimated Enrollment:	24
Study Start Date:	November 2007
Estimated Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the safety and maximum tolerated dose of EGFRBi-armed autologous activated T-cells (ATC) when administered in combination with low-dose aldesleukin and sargramostim (GM-CSF) in patients with recurrent, refractory, or extensive (metastatic) non-small cell lung cancer (NSCLC).

Secondary

Assess clinical outcome based on tumor responses, overall survival, and progression-free survival.
Monitor changes in sera concentrations of the tumor marker in association with EGFRBi-armed ATC administration throughout the study and at time points thereafter in patients with elevated levels of carcinoembryonic antigen (CEA) prior to beginning the study.
Monitor patient sera for human anti-mouse antibodies (HAMA).
Evaluate immune response, which may reflect immune augmentation in response to EGFRBi-armed ATC infusions, in peripheral blood mononuclear cell (PBMC) samples as well as purified immune cell populations.
Investigate proliferation in response to ex vivo stimulation with NSCLC tumor-associated antigens, sera cytokine profiles (Th1 vs Th2), cytotoxicity of patient PBMC, and interferon gamma ELISPOTS as a surrogate marker for assessing generation of EGFR-specific cytotoxic T-lymphocytes (CTL).

OUTLINE: Peripheral blood mononuclear cells (PBMCs) are collected by 1 or 2 leukaphereses for the generation of activated T cells (ATCs). The PBMCs are activated with OKT3 (anti-CD3) and expanded in aldesleukin for up to 14 days. The ATCs are then armed with EGFRBi.

Patients receive EGFRBi-armed autologous ATCs IV over 30-60 minutes twice weekly for 4 weeks (a total of 8 infusions) in the absence of disease progression or unacceptable toxicity. Patients also receive low-dose aldesleukin subcutaneously (SC) once daily and sargramostim (GM-CSF) SC twice weekly beginning 3 days before the first ATC infusion and continuing for 1 week after the last ATC infusion.

After completion of study therapy, patients are followed periodically.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)
- Recurrent, refractory, or metastatic disease after ≥ 1 prior first-line regimen (chemotherapy or radiotherapy)
Documented EGFR-positive disease (any expression level) by immunohistochemistry (IHC) (may be based on archival sample)
Measurable or evaluable disease by radiograph, CT scan, MRI, and/or physical exam
Appropriate slides of the primary lesion must be available for review of IHC staining assessment by a central pathology team
No clinical evidence of active brain metastases
- Patients with brain metastases are eligible provide they have received definitive radiotherapy or chemotherapy and/or have undergone surgical resection for brain metastases
No prior hematological malignancy

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 60-100% OR ECOG PS 0-2
Life expectancy ≥ 3 months
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Granulocytes ≥ 1,000/mm^3
Platelet count ≥ 50,000/mm^3
Hemoglobin ≥ 8 g/dL
BUN ≤ 2.0 times normal
Serum creatinine ≤ 2.0 mg/dL
Bilirubin ≤ 1.5 times normal
SGOT ≤ 1.5 times normal (with or without liver metastases)
Hepatitis B surface antigen and HIV negative
LVEF ≥ 45 % at rest (by MUGA)
- No evidence of depressed left ventricular function
FEV_1, DLCO, and FVC ≥ 50% of the predicted value
No other malignancy, except for the following:
- History of curatively treated in situ squamous cell carcinoma or basal cell carcinoma of the skin
- History of other curatively treated malignancy (except those with a hematologic origin) for which the patient has remained in complete remission > 5 years after completing therapy (as documented by history, physical exams, tumor markers, and radiology scanning)
No serious medical or psychiatric illness that would preclude giving informed consent or receiving intensive treatment
No recent myocardial infarction (within the past year)
No current angina/coronary symptoms requiring medications
No clinical evidence of congestive heart failure requiring medical management (irrespective of MUGA results)
No systolic blood pressure (BP) ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg
- Patients with elevated BP must have it controlled by anti-hypertensive medications for at least 7 days prior to the first infusion

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
More than 4 weeks since prior chemotherapy or radiotherapy
At least 4 weeks since prior cetuximab or small molecule EGFR-inhibitors including, but not limited to, gefitinib or erlotinib hydrochloride
No concurrent radiotherapy
No concurrent steroids except for treatment of adrenal failure, septic shock, or pulmonary toxicity or hormones for non-disease-related conditions (e.g., insulin for diabetes)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00569296

Locations

United States, Rhode Island
Roger Williams Medical Center	Recruiting
Providence, Rhode Island, United States, 02908-4735
Contact: Abby Maizel, MD, PhD 401-456-2698

Sponsors and Collaborators

Roger Williams Medical Center

National Cancer Institute (NCI)

Investigators

Study Chair:

Abby Maizel, MD, PhD

Roger Williams Medical Center

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000577502, RWMC-RWH-07-349-32
Study First Received:	December 6, 2007
Last Updated:	December 16, 2008
ClinicalTrials.gov Identifier:	NCT00569296
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

recurrent non-small cell lung cancer
stage IV non-small cell lung cancer

Study placed in the following topic categories:

Thoracic Neoplasms
Non-small cell lung cancer
Aldesleukin
Respiratory Tract Diseases
Lung Neoplasms
Lung Diseases

Cetuximab
Carcinoma, Non-Small-Cell Lung
Recurrence
Neoplasms, Glandular and Epithelial
Carcinoma

Additional relevant MeSH terms:

Anti-Infective Agents
Respiratory Tract Neoplasms
Neoplasms
Anti-HIV Agents
Neoplasms by Site
Neoplasms by Histologic Type

Anti-Retroviral Agents
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009