Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and Sargramostim (GM-CSF) in Treating Advanced Solid Tumors
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 advanced solid tumors.
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 Solid Tumors|
- Maximum tolerated dose of EGFRBi-armed autologous activated T-cells [ Time Frame: 5 week regimen with 2 month follow up ] [ Designated as safety issue: Yes ]
- Determine potential side effects of treating patients with Armed Activated T Cells (ATC) [ Time Frame: 5 week regimen with 2 month follow up ] [ 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: 5 week regimen with 2 month follow up ] [ Designated as safety issue: No ]
- Determination of immunologic changes by evaluation of phenotypes of peripheral blood mononuclear cells before and after immunotherapy [ Time Frame: 5 week regimen with 2 month follow up ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 5 week regimen wtih 2 month follow up ] [ Designated as safety issue: No ]
- Progression-free survival [ Time Frame: 5 week regimen with 2 month follow up ] [ Designated as safety issue: No ]
- Determination of immunologic changes by evaluation of peripheral blood lymphocytes [ Time Frame: 5 week regimen with 2 month follow up ] [ Designated as safety issue: No ]
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||February 2015|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Armed Activated T Cells
Activated T Cells (ATC) armed with the bispecific antibody OKT3 x Cetuximab (EGFRBi). ATC will be expanded for 14 days from a leukapheresis product, armed with EGFRBi, cryopreserved and infused in 8 divided doses. Patients will also receive low dose subcutaneous IL-2(3000,000 IU/m2/day) and GM-CSF (250ug/m2 twice per week)
Biological: EGFRBi-armed autologous activated T cells
EGFRBi-armed autologous activated T cells infused twice a week for 4 weeks for a total of 8 infusions. The doses of the armed ATC will be escalated at the dose levels of 5, 10, 20, and 40 billion armed ATC per infusion. Subcutaneous aldesleukin (300,000IU/m2/day) and Sargramostim (250 ug/m2 twice per week) both starting 3 days before the 1st infusion and ending 7 days after the last dose of armed ATC.
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) advanced solid tumors.
Assess clinical outcome based on tumor responses, overall survival, and progression-free survival.
Monitor changes in sera concentrations of the tumor-associated biomarkers respective of the primary neoplasm (i.e. carcinoembryonic antigen(CEA); prostate specific antigen (PSA); Her2/neu (HER2); etc.) in association with EGFRBi-armed ATC administration throughout the study and at time points thereafter.
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 tumor-specific 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.
NOTE: For the purpose of determining safety and maximum tolerated dose of EGFRBi-armed ATC, patients enrolled at each dose level from this study will be combined with patients enrolled at each dose level in RWH 349-32 (NCT00569296): 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 (NSCLC) to count toward each dose level cohort. A total of three patients enrolled form either of the two trials will be treated at each dose level, but at least one NSCLC patient representative from protocol 349-32 will be enrolled and evaluated at each dose level.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01081808
|Contact: Robin Davies, RNfirstname.lastname@example.org|
|United States, Rhode Island|
|Roger Willaims Medical Center||Recruiting|
|Providence, Rhode Island, United States, 02908|
|Contact: Robin Davies, RN 401-456-2419 email@example.com|
|Principal Investigator: Abby Maizel, MD,PhD|
|Study Chair:||Abby Maizel, MD,PhD||Roger William Medical Center|