Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and Sargramostim (GM-CSF) in Treating Advanced Solid Tumors

Neoplasms Clinical Trial

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

Status Terminated

Clinical Trial 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 advanced solid tumors.

Clinical Trial 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) advanced solid tumors.

Secondary

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. ;

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metastatic Cancer
• Neoplasm Metastasis
• Neoplasms
• Solid Tumors
• Tumors

• NCT number: NCT01081808
• Study type: Interventional
• Source: Roger Williams Medical Center
• Status: Terminated
• Phase: Phase 1
• Start date: October 2009
• Completion date: February 2015