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TerminatedNCT00569296Updated Mar 25, 2015

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

A Phase 1 interventional study of EGFRBi-armed autologous activated T cells and aldesleukin in Lung Cancer, sponsored by Roger Williams Medical Center. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-03-25.

Sponsored by Roger Williams Medical Center · Phase 1, Interventional, and Treatment

Why this study was terminated
Funding ended
Phase
Phase 1
Study type
Interventional
Enrollment
5
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

FUNDING SOURCE--FDA OOPD

Read the 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.

02

Conditions studied

  • Lung Cancer

Keywords

  • recurrent non-small cell lung cancer
  • stage IV non-small cell lung cancer
03

In context

Lung Neoplasms

7,243 studies on the registry are indexed under Lung Neoplasms; 1,558 are open to participants now.

This study's enrollment of 5 is below the median of 60 across 5,296 interventional studies indexed under Lung Neoplasms.

Browse Lung Neoplasms studies →

Lead sponsor

Roger Williams Medical Center is the lead sponsor of 17 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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)
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
5 participants (actual)

Study arms

  • Experimental
    T-cells

    EGFRBi-armed autologous activated T cells

    Biological: EGFRBi-armed autologous activated T cells · Biological: aldesleukin · Biological: sargramostim

Interventions

  • BiologicalEGFRBi-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.

  • Biologicalaldesleukin

    300,00IU/m2/day beginning 3 days before the first Activated T-cell infusion and ending 1 week after the last infusion

    Also known as: IL-2

  • Biologicalsargramostim

    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

    Also known as: GM-CSF

06

What researchers measure

Primary outcomes

  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 outcomes

  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

07

Study locations

1 site
  • Roger Williams Medical Center
    Providence, Rhode Island 02908-4735, United States
08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 25, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00569296
Lead sponsor
Roger Williams Medical Center
Responsible party
Sponsor
First posted
Dec 7, 2007
Start date
Nov 2007
Primary completion
Dec 2014
Completion
Mar 2015
Last update
Mar 25, 2015

Study contacts

Abby Maizel, MD, PhD
study chair · Roger Williams Medical Center

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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