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
- 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
- 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
- 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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Abby Maizel, MD, PhD
Roger Williams Medical Center
United States: Food and Drug Administration
|Roger Williams Medical Center||Providence, Rhode Island 02908-4735|