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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00569296
Recruitment Status : Terminated (Funding ended)
First Posted : December 7, 2007
Last Update Posted : March 25, 2015
Information provided by (Responsible Party):
Roger Williams Medical Center

Brief Summary:

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 or disease Intervention/treatment Phase
Lung Cancer Biological: EGFRBi-armed autologous activated T cells Biological: aldesleukin Biological: sargramostim Phase 1

Detailed Description:



  • 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).


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: 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
Study Start Date : November 2007
Actual Primary Completion Date : December 2014
Actual Study Completion Date : March 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
Drug Information available for: Aldesleukin

Arm Intervention/treatment
Experimental: T-cells
EGFRBi-armed autologous activated T cells
Biological: EGFRBi-armed autologous activated T cells
Dose escalation, dosage depends on when entered in study. 8 infusions (twice a week over 4 weeks. Each infusion will be over at least 1 hour.

Biological: aldesleukin
300,00IU/m2/day beginning 3 days before the first Activated T-cell infusion and ending 1 week after the last infusion
Other Name: IL-2

Biological: sargramostim
250 micrograms/m2/twice weekly beginning 3 days before the first activated T-cell infusion and ending 1 week after the last Activated T-cell infusion
Other Name: GM-CSF

Primary Outcome Measures :
  1. Safety [ Time Frame: 4 weeks ]
  2. Maximum tolerated dose of EGFRBi-armed autologous activated T-cells [ Time Frame: 4 weeks ]
  3. Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro [ Time Frame: 4 weeks ]

Secondary Outcome Measures :
  1. Overall survival [ Time Frame: 2 years ]
  2. Progression-free survival [ Time Frame: 2 years ]
  3. 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 [ Time Frame: 4 weeks ]
  4. Determination of immunologic changes by evaluation of peripheral blood lymphocytes [ Time Frame: 4 weeks ]
  5. 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 [ Time Frame: 4 weeks ]
  6. Determination of immunologic changes by evaluation of phenotypes of peripheral blood mononuclear cells before and after immunotherapy [ Time Frame: 4 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00569296

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United States, Rhode Island
Roger Williams Medical Center
Providence, Rhode Island, United States, 02908-4735
Sponsors and Collaborators
Roger Williams Medical Center
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Study Chair: Abby Maizel, MD, PhD Roger Williams Medical Center
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Responsible Party: Roger Williams Medical Center
ClinicalTrials.gov Identifier: NCT00569296    
Other Study ID Numbers: CDR0000577502
349-32 ( Other Identifier: Roger Williams Medical Center )
3422 ( Other Grant/Funding Number: FDA OOPD )
First Posted: December 7, 2007    Key Record Dates
Last Update Posted: March 25, 2015
Last Verified: March 2015
Keywords provided by Roger Williams Medical Center:
recurrent non-small cell lung cancer
stage IV non-small cell lung cancer
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents