Laboratory-Treated Autologous Lymphocytes, Aldesleukin, and GM-CSF in Treating Patients With Recurrent, Refractory, or Metastatic Non-Small Cell Lung Cancer

NCT ID: NCT00569296

Last Updated: 2015-03-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-11-30
• Study Completion Date: 2015-03-31

Brief 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 non-small cell lung cancer.

FUNDING SOURCE--FDA OOPD

Detailed 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) 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.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

T-cells

EGFRBi-armed autologous activated T cells

Group Type: EXPERIMENTAL

EGFRBi-armed autologous activated T cells

Intervention Type: BIOLOGICAL

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.

aldesleukin

Intervention Type: BIOLOGICAL

300,00IU/m2/day beginning 3 days before the first Activated T-cell infusion and ending 1 week after the last infusion

sargramostim

Intervention Type: BIOLOGICAL

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

Interventions

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.

Intervention Type: BIOLOGICAL

aldesleukin

300,00IU/m2/day beginning 3 days before the first Activated T-cell infusion and ending 1 week after the last infusion

Intervention Type: BIOLOGICAL

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

Intervention Type: BIOLOGICAL

Other Intervention Names

IL-2; GM-CSF

Eligibility Criteria

Inclusion Criteria

• 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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Roger Williams Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Abby Maizel, MD, PhD

Role: STUDY_CHAIR

Roger Williams Medical Center

Locations

Roger Williams Medical Center

Providence, Rhode Island, United States

Countries

United States

Other Identifiers

349-32

Identifier Type: OTHER

Identifier Source: secondary_id

3422

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

CDR0000577502

Identifier Type: -

Identifier Source: org_study_id