DNP-Modified Autologous Tumor Cell Vaccine for Resectable Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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To determine if a vaccine made from patient's own tumor tissue can stimulate an immune response against the patient's tumor cells. To determine the safety of the vaccine

Detailed Description
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Study Objectives: To study the toxicity, safety and delayed-type hypersensitivity (DTH) responses of DNP-modified autologous tumor cell vaccine (L-Vax) in patients with resectable NSCLC: To determine the tolerability and toxicity of L-Vax To determine whether L-Vax induces a DTH response to autologous, DNP-modified NSCLC cells of similar magnitude to responses observed with melanoma Determine whether L-Vax induces a DTH response to autologous unmodified NSCLC cells To determine whether the DTH responses to autologous, unmodified NSCLC cells that have been fixed with ethanol correlate with DTH responses to autologous, unmodified NSCLC cells that are not fixed Study Population: Patients with resectable NSCLC whose therapeutic tumor surgery provides a mass, which yields adequate tumor, cells for vaccine preparation and DTH testing Study Design: A Phase I/IIa double-blind, three-dose, single center study Investigational Product: L-Vax: DNP-modified autologous NSCLC cell vaccine Dosage Form: Cell suspension Route of Administration: Intradermal Dosage and Treatment Schedule: Prior to vaccine administration, patients will be tested for DTH to autologous NSCLC cells that have been: DNP-modified, or unmodified and irradiated, or unmodified and irradiated and fixed with ethanol (if sufficient cells available) Three doses of vaccine will be tested: 5 x 105, 2.5 x 106, or 5 x 106 DNP-modified autologous NSCLC cells. An initial dose of DNP-modified autologous NSCLC cells* without Bacillus of Calmette and Guérin (BCG) followed by cyclophosphamide (CY) then weekly doses of DNP-modified autologous NSCLC tumor cells mixed with BCG for 6 weeks, and completed with one dose of DNP-modified autologous NSCLC tumor cells mixed with BCG as a 6-month booster, if adequate number of cells available. count determined prior to aliquoting for cryopreservation Endpoints: Treatment-emergent and related adverse events, serious adverse events, and Grade 3 and 4 laboratory abnormalities for safety assessments Other Parameters: · DTH skin reactions for assessing the induction of immune responses to DNP-modified and unmodified autologous NSCLC tumor cells· Survival· Exploratory analysis of in vitro studies of peripheral blood lymphocytes obtained from study subjects Duration of Treatment: Up to 9 months Duration of Subject Participation in Study: Three months from the patient's last vaccine Duration of Follow-up: Survival information and disease status will be collected via phone or visit on a quarterly basis for each patient beginning 30 days after the last scheduled visit until the last patient has been followed for three months from his/her last vaccine Number of Subjects Required to Meet Protocol Objectives: Up to 42 evaluable subjects Number of Study Centers: Three Number of Individual Blood Draws: 15 draws over nine months Volume of Blood Drawn: 13 Draws of 30 mL/draw (total 360 mL) and two draws of 50mL in heparinized tubes

Official Title
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L-Vax: A Feasibility Study Using a DNP-Modified Autologous Tumor Cell Vaccine as Therapy in Patients With Resectable Non-Small Cell Lung Cancer

Conditions
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Non-Small Cell Lung Cancer - Completely Resectable

Intervention / Treatment
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* Biological: L-Vax: Autologous, DNP-Modified NSCLC Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented stage IA, IB, IIA, IIB or IIIA NSCLC that is completely resectable and does not require post-operative radiation therapy or peri-operative chemotherapy Excision of the tumor and harvesting of tumor mass yielding adequate cells for vaccine manufacture and DTH testing Successful preparation and lot release of vaccines and of DTH testing material containing DNP-modified tumor cells Minimum of 3 and maximum of 8 weeks since the surgery Expected survival of at least 6 months Karnofsky performance status ³ 80 Signed informed consent Exclusion Criteria: Alkaline phosphatase > 2.5 x ULN Total bilirubin > 2.0 mg/dL Creatinine > 2.0 mg/dL Hemoglobin < 10.0 g/dL WBC < 3,000 /mm3 Platelet count < 100,000/mm3 Chemotherapy - pre-operative or post-operative (except as designated in protocol) Radiation therapy to lung - pre-operative or post-operative Any major field radiotherapy within 6 months prior to participation in the study Immunotherapy (interferons, tumor necrosis factor, other cytokines [e.g., interleukins], biological response modifiers, or monoclonal antibodies) within 4 weeks prior to participation in the study Prior splenectomy Concurrent use of systemic steroids, except for the period of administration of the adjuvant chemotherapy, as per Section 8.6 (months 4-7)(Note: Topical steroid therapies [applied to the skin] are allowed, provided these are not applied to limbs injected with vaccine or skin test materials. Inhaled aerosol steroids are allowed.) Concurrent use of immunosuppressive drugs, except for the period of administration of the adjuvant chemotherapy (months 4-7) Concurrent use of antitubercular drugs (isoniazid, rifampin, streptomycin) Other malignancy within 5 years except curatively treated non-melanomatous skin cancer and curatively treated carcinoma in situ of the uterine cervix, or early stage (stage A or B1) prostate cancer Concurrent autoimmune diseases, e.g., systemic lupus erythematosus, multiple sclerosis or ankylosing spondylitis Concurrent medical condition that would preclude compliance or immunologic response to study treatment Concurrent serious infection or other serious medical condition Receipt of any investigational medication within 4 weeks prior to participation in the study Pregnancy or lactation (serum b-human chorionic gonadotropin [b-HCG] test must be negative in fertile women at screening visit) Active tuberculosis or a past history of tuberculosis PPD positive (³ 5 mm to 5TU) Known gentamicin sensitivity Anergic, defined by the inability to make a DTH to at least one of the following: candida, mumps, tetanus or trichophyton (based, except for the period of administration of the adjuvant chemotherapy (months 4-7) upon availability) Vaccine lot release failure
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>5 million autologous, DNP-modified NSCLC cells | Biological: L-Vax: Autologous, DNP-Modified NSCLC Vaccine<br>* autologous, DNP-modified NSCLC cells in suspension dosage - depends on arm route - intradermal frequency - weekly x7, booster at 6 months<br>|
| Experimental: 2<br>2.5 million autologous, DNP-modified NSCLC cells | Biological: L-Vax: Autologous, DNP-Modified NSCLC Vaccine<br>* autologous, DNP-modified NSCLC cells in suspension dosage - depends on arm route - intradermal frequency - weekly x7, booster at 6 months<br>|
| Experimental: 3<br>0.5 million autologous, DNP-modified NSCLC cells | Biological: L-Vax: Autologous, DNP-Modified NSCLC Vaccine<br>* autologous, DNP-modified NSCLC cells in suspension dosage - depends on arm route - intradermal frequency - weekly x7, booster at 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cell-mediated immunity to autologous tumor cells. |  | 3 months | 
| Safety |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vaccine, lung cancer, non-small cell lung cancere, immunotherapy