Lung Cancer
Conditions
Keywords
stage I non-small cell lung cancer, stage II non-small cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, bronchoalveolar cell lung cancer
Brief summary
RATIONALE: Vaccines made from a person's white blood cells and allogeneic tumor cells may make the body build an effective immune response to kill tumor cells. PURPOSE: This phase II trial is studying how well vaccine therapy works in treating patients with stage I, stage II, or stage III non-small cell lung cancer.
Detailed description
OBJECTIVES: * Determine the immunologic effects of adjuvant vaccine therapy comprising autologous dendritic cells loaded with allogeneic non-small cell lung cancer (NSCLC) cells in patients with unresectable stage IIIA or IIIB, or resected stage I-IIIB NSCLC. * Determine the potential clinical efficacy of this vaccine in these patients. OUTLINE: This is an open-label study. Patients are stratified according to type of prior primary therapy (surgical vs nonsurgical). Patients undergo leukapheresis over 3-4 hours to harvest mononuclear cells for the production of dendritic cells (DC). DC are then pulsed with allogeneic non-small cell lung cancer cells to produce an autologous dendritic cell vaccine. Patients receive vaccine intradermally once a month for 2 months in the absence of disease recurrence or unacceptable toxicity. Patients are followed monthly for 4 months, every 6 months for 2 years, and then periodically thereafter. PROJECTED ACCRUAL: A total of 60 patients (30 per stratum) will be accrued for this study within 3 years.
Interventions
BIOLOGICALautologous dendritic cell cancer vaccine
Dendritic cells made from white blood cells obtained through out-patient leukapheresis procedure. Vaccine given by injection under the skin in the front, upper thigh. Two vaccine injections total, given one month a part.
Sponsors
National Cancer Institute (NCI)
Edward Hirschowitz
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed non-small cell lung cancer (NSCLC) * Meets 1 of the following stage criteria: * Completely resected stage I-IIIB disease * Underwent surgical resection \> 4 weeks but ≤ 4 years ago * Unresectable stage IIIA or IIIB disease AND previously treated with definitive radiotherapy or chemotherapy \> 6 weeks ago * Bronchoalveolar carcinomas allowed * Clinically stable disease by chest x-ray or CT scan within the past 6 weeks * No progressive disease * No malignant pleural or pericardial effusions PATIENT CHARACTERISTICS: Age * 18 to 80 Performance status * ECOG 0-1 Life expectancy * Not specified Hematopoietic * Hemoglobin ≥ 9.0 g/dL Hepatic * Bilirubin ≤ 2.5 times upper limit of normal (ULN) * AST and ALT ≤ 2.5 times ULN * No known history of infectious hepatitis Renal * Creatinine ≤ 3 mg/dL * Ionized calcium ≥ 0.9 mmol/L (may be replaced) Cardiovascular * No known New York Heart Association class III-IV congestive heart failure * No hemodynamically significant valvular heart disease * No myocardial infarction within the past 6 months * No active angina pectoris * No uncontrolled ventricular arrhythmia * No stroke within the past year * No known cerebrovascular disease * No other significant cardiac disease by echocardiogram, stress test, or risk assessment by cardiologist (for patients suspected of cardiac disease by history or physical exam) Immunologic * No known HIV positivity * No other immunosuppressive disorders, including chronic disorders Other * Not pregnant * Negative pregnancy test * Potassium ≥ 3.0 mEq/L (may be replaced) * Able to tolerate modest blood volume and electrolyte shifts during leukapheresis * No other malignancy PRIOR CONCURRENT THERAPY: Biologic therapy * Prior biologic therapy allowed * Other concurrent biologic therapy allowed Chemotherapy * See Disease Characteristics * No concurrent chemotherapy Endocrine therapy * No concurrent steroids during and for 16 weeks after study treatment Radiotherapy * See Disease Characteristics * No concurrent radiotherapy Surgery * See Disease Characteristics Other * Prior neoadjuvant or adjuvant therapy for surgically resected patients allowed * No concurrent shorter courses of immunosuppressive medications during and for 16 weeks after study treatment * No concurrent chronic immunosuppressive medications * Concurrent cyclooxygenase-2 inhibitors allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Showing Immunologic Response to Vaccine Within Six Months of Immunization | six months post vaccine | Antigen specific reaction is measured serially in blood of each participant prior to and through six months post-vaccine. Increase in levels of specific T cell activity from pre vaccine to post vaccine serve as primary measures of an individual's response to vaccine. The number (relative percent) of participants achieving immunologic response to vaccine within 6 month of immunization was the dominant metric of vaccine activity within the study population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Alive Five Years Post Vaccine | five years post vaccine | Documentation of radiographic surveillance for recurrence or progression for 5 years post-vaccine |
Countries
United States
Participant flow
Recruitment details
Non-randomized open label; stage I-IIIB NSCLC. Closed to accrual in 2006 when defined phase I immunological endpoints were reached.
Pre-assignment details
None excluded; all completed.
Participants by arm
| Arm | Count |
|---|---|
| Vaccine therapeutic autologous dendritic cells : Dendritic cells made from white blood cells obtained through out-patient leukapheresis procedure. Vaccine given by injection under the skin in the front, upper thigh. Two vaccine injections total, given one month a part. | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | Vaccine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Age, Continuous | 60 years STANDARD_DEVIATION 5 |
| Region of Enrollment Israel | 1 participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
Primary
Number of Participants Showing Immunologic Response to Vaccine Within Six Months of Immunization
Antigen specific reaction is measured serially in blood of each participant prior to and through six months post-vaccine. Increase in levels of specific T cell activity from pre vaccine to post vaccine serve as primary measures of an individual's response to vaccine. The number (relative percent) of participants achieving immunologic response to vaccine within 6 month of immunization was the dominant metric of vaccine activity within the study population.
Time frame: six months post vaccine
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaccine | Number of Participants Showing Immunologic Response to Vaccine Within Six Months of Immunization | 22 participants with immunological response |
Secondary
Number of Participants Alive Five Years Post Vaccine
Documentation of radiographic surveillance for recurrence or progression for 5 years post-vaccine
Time frame: five years post vaccine
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaccine | Number of Participants Alive Five Years Post Vaccine | 20 participants |