Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and GM-CSF in Treating Patients With Recurrent, Refractory, or Metastatic Non-Small Cell Lung Cancer
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
Biological: EGFRBi-armed autologous activated T cells
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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|
- Safety [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
- Maximum tolerated dose of EGFRBi-armed autologous activated T-cells [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
- Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: 2 years ] [ 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 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
- Determination of immunologic changes by evaluation of peripheral blood lymphocytes [ Time Frame: 4 weeks ] [ 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 [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
- Determination of immunologic changes by evaluation of phenotypes of peripheral blood mononuclear cells before and after immunotherapy [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||November 2007|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||May 2015 (Final data collection date for primary outcome measure)|
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-2Biological: 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
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00569296
|Contact: Robin Davies, RNfirstname.lastname@example.org|
|United States, Rhode Island|
|Roger Williams Medical Center||Recruiting|
|Providence, Rhode Island, United States, 02908-4735|
|Contact: Robin Davies, RN 401-456-2419 RDavies@chartercare.org|
|Study Chair:||Abby Maizel, MD, PhD||Roger Williams Medical Center|