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

NCT00569296 | Terminated Phase 1 DMC

• 3 other identifiers: CDR0000577502349-323422
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

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

Conditions

Lung Cancer

Keywords

recurrent non-small cell lung cancer; stage IV non-small cell lung cancer

Outcome Measures

Primary Outcomes (3)

• Safety

  4 weeks

• Maximum tolerated dose of EGFRBi-armed autologous activated T-cells

  4 weeks

• Determination of immunologic changes by evaluation of cytokine profiles obtained before and after stimulation with OKT3 in vitro

  4 weeks

Secondary Outcomes (6)

• Overall survival

  2 years

• Progression-free survival

  2 years

• 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

  4 weeks

• Determination of immunologic changes by evaluation of peripheral blood lymphocytes

  4 weeks

• 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

  4 weeks

Study Arms (1)

T-cells

EXPERIMENTAL

EGFRBi-armed autologous activated T cells

Biological: EGFRBi-armed autologous activated T cells; Biological: aldesleukin; Biological: sargramostim

Interventions

EGFRBi-armed autologous activated T cells 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.

T-cells

aldesleukin BIOLOGICAL

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

Also known as: IL-2

T-cells

sargramostim 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

Also known as: GM-CSF

T-cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) * Recurrent, refractory, or metastatic disease after ≥ 1 prior first-line regimen (chemotherapy or radiotherapy) * Documented EGFR-positive disease (any expression level) by immunohistochemistry (IHC) (may be based on archival sample) * Measurable or evaluable disease by radiograph, CT scan, MRI, and/or physical exam * Appropriate slides of the primary lesion must be available for review of IHC staining assessment by a central pathology team * No clinical evidence of active brain metastases * Patients with brain metastases are eligible provide they have received definitive radiotherapy or chemotherapy and/or have undergone surgical resection for brain metastases * 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)

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Roger Williams Medical Center: lead

Study Sites (1)

Roger Williams Medical Center

Providence, Rhode Island, 02908-4735, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

aldesleukin; Interleukin-2; sargramostim; Granulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors

Study Officials

• Abby Maizel, MD, PhD

  Roger Williams Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2007
• First Posted: December 7, 2007
• Study Start: November 1, 2007
• Primary Completion: December 1, 2014
• Study Completion: March 1, 2015
• Last Updated: March 25, 2015

Record last verified: 2015-03

Locations

US (1)