A Phase I Clinical Trial of Mature Autologous Dendritic Cells Loaded With Irradiated Autologous Tumor Cells for the Treatment of Non-Small Cell Lung Cancer (NSCLC)
18 Years
N/A
Both
Lung Cancer
Trial Information
A Phase I Clinical Trial of Mature Autologous Dendritic Cells Loaded With Irradiated Autologous Tumor Cells for the Treatment of Non-Small Cell Lung Cancer (NSCLC)
OBJECTIVES:
Primary
- Determine the maximum tolerated dose of adjuvant autologous dendritic cells loaded with
irradiated autologous tumor cells in patients with stage IB-IIIA non-small cell lung
cancer undergoing resection.
- Determine the safety and tolerability of this vaccine in these patients.
Secondary
- Determine the feasibility of this vaccine in these patients.
- Determine vaccine-specific and antitumor immunity in patients treated with this
vaccine.
OUTLINE: This is a dose-escalation study.
Patients undergo leukaphersis to isolate peripheral blood mononuclear cells (PBMC). PBMC are
expanded ex vivo to generate monocyte-derived dendritic cells (DC). Autologous tumor cells
are harvested and purified at the time of surgical resection. DC are then loaded with
irradiated autologous tumor cells.
Within 4-8 weeks after surgical resection, patients receive autologous DC loaded with
irradiated autologous tumor cells intradermally on approximately days 1, 30, and 60 in the
absence of unacceptable toxicity.
Cohorts of 6-9 patients receive escalating doses of vaccine until the maximum tolerated dose
(MTD) is determined. If 2 of 9 patients in the first cohort experience dose-limiting
toxicity, that dose level is considered the MTD.
Patients are followed at approximately 1 and 4 months, and then every 6 months for 4 years.
PROJECTED ACCRUAL: A total of 12-15 patients will be accrued for this study within 18
months.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of non-small cell lung cancer
- Clinical stage IB-IIIA disease
- Candidate for surgical resection as primary treatment for tumor
- Surgically resectable tumor ≥ 2.0 cm in diameter
- No brain metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Zubrod 0-1
Life expectancy
- Not specified
Hematopoietic
- Platelet count ≥ 100,000/mm^3
- WBC ≥ 3,000/mm^3
- Absolute neutrophil count ≥ 1,500/mm^3
- Hematocrit ≥ 30%
Hepatic
- Hepatitis B surface antigen negative*
- Hepatitis B core antigen negative*
- Hepatitis C virus negative*
- Bilirubin ≤ 2.0 mg/dL
- AST and ALT ≤ 2 times upper limit of normal NOTE: *Screening performed only if liver
enzymes are elevated
Renal
- Creatinine ≤ 2.2 mg/dL
- BUN ≤ 40 mg/dL
Pulmonary
- FEV_1 > 2.0 L (pre-resection) OR
- Predicted post-resection FEV_1 > 1.0 L
- No more than 2 chronic obstructive pulmonary disease exacerbations requiring > 2
weeks of oral steroids and/or hospitalization within the past year
Immunologic
- Purified protein derivative (PPD) skin test negative
- HIV-1 and HIV-2 negative
- No acute infection, including any acute viral, bacterial, or fungal infection
requiring specific therapy within the past 7 days
- No allergy to study agents
- No known autoimmune or collagen vascular disorder
Other
- Not pregnant or nursing
- Fertile patients must use effective contraception
- No other malignancy within the past 5 years except adequately treated basal cell or
squamous cell skin cancer or carcinoma in situ of the cervix
- No underlying condition that would preclude study therapy
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent anti-tumor necrosis factor agents
Chemotherapy
- Standard adjuvant chemotherapy for lung cancer allowed provided therapy is completed
≥ 30 days before administration of the first study vaccine
- No concurrent cyclophosphamide
Endocrine therapy
- No concurrent high-dose corticosteroids (e.g., > 10 mg of prednisone)
- Concurrent corticosteroids for minor breathing exacerbations allowed provided patient
receives ≤ 2 short courses (≤ 10 days per course) within a 45-day period
- No concurrent corticosteroids within 48 hours before or after study vaccine
administration
Radiotherapy
- Standard adjuvant radiotherapy for lung cancer allowed provided therapy is completed
≥ 30 days before administration of the first study vaccine
Surgery
- No prior organ allograft
Other
- No concurrent antihistamines within 48 hours before or after study vaccine
administration
- No concurrent cimetidine or other H2 blockers within 48 hours before or after study
vaccine administration
- Concurrent antibiotics for minor infection allowed provided patient receives ≤ 2
short courses (≤ 10 days per course) within a 45-day period
- No concurrent cyclosporine
- No concurrent azathioprine
- No other concurrent drugs known to significantly alter immune function
- No concurrent cytotoxic therapy
- No concurrent participation in another clinical trial involving experimental therapy
- No other concurrent anticancer therapy
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Michael D. Roth, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
Unspecified
Study ID:
CDR0000396774
NCT ID:
NCT00098917
Start Date:
February 2005
Completion Date:
Related Keywords:
- Lung Cancer
- stage I non-small cell lung cancer
- stage II non-small cell lung cancer
- stage IIIA non-small cell lung cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
Name | Location |
|---|---|
| Jonsson Comprehensive Cancer Center at UCLA | Los Angeles, California 90095-1781 |
