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
18 Years
N/A
Both
Lung Cancer
Trial Information
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
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.
Inclusion 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)
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety
Outcome Time Frame:
4 weeks
Safety Issue:
Yes
Principal Investigator
Abby Maizel, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Roger Williams Medical Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000577502
NCT ID:
NCT00569296
Start Date:
November 2007
Completion Date:
December 2013
Related Keywords:
- Lung Cancer
- recurrent non-small cell lung cancer
- stage IV non-small cell lung cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| Roger Williams Medical Center | Providence, Rhode Island 02908-4735 |
