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| ID | Type | Description | Link |
|---|---|---|---|
| P30CA076292 | U.S. NIH Grant/Contract | View source | |
| NIH-OBA-0608-801 | Other Identifier | National Institute of Health |
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| Name | Class |
|---|---|
| National Cancer Institute (NCI) | NIH |
| National Institutes of Health (NIH) | NIH |
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The purpose of this study is to find out what effects (good and/or bad) a tumor vaccine used in combination with two drugs (ATRA and cytoxan) have on the patient and their cancer. We also want to find out if the vaccine and the drugs can boost the patient's immune system and how their immune system reacts, both before and after the vaccine treatment.
This protocol describes a phase II study involving patients with stage IV adenocarcinoma of the lung. Treatment will consist of Cyclophosphamide (300 mg/m²) to be given IV on day 1 and day 57. On day 4 immunization with intradermal vaccine injections at 4 separate sites (bilateral upper arms and bilateral upper thighs will be repeated every 14 days times 2 followed by every 28 days times 3 (day 4, 18, 32, 60, 88, and 116). Decavac (tetanus shot) 0.5 cc intramuscular (IM) will be given after the first vaccine. ATRA (150 mg/m2/day) oral three times daily (TID) dosing administered after the first and fourth vaccines (day 5-7 & day 61-63). Those patients achieving stable disease (SD), partial response (PR), or complete response (CR) at restaging after the initial 6 vaccines will receive additional vaccines every 3 months until disease progression. The vaccine will consist of GM.CD40L bystander cells admixed with an equivalent number of the 2 allogeneic tumor cell lines. There will be a +/- 7 day window for all study related exams, tests, and procedures.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Combination Immunotherapy | Experimental | Vaccine + Cytoxan + ATRA as outlined in Detailed Description |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vaccine Treatment | Biological | We created a vaccine in which irradiated allogeneic lung adenocarcinoma cells are combined with a bystander K562 cell line transfected with hCD40L and hGM-CSF. By recruiting and activating dendritic cells, we hypothesized the vaccine would induce tumor regression in metastatic lung adenocarcinoma. Intradermal vaccine was given every 14 days x3, followed by monthly x3. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Evaluable Participants With Tumor Response | Number of participants with evaluable peripheral blood mononuclear cells (PBMCs) who demonstrated sustained tumor peptide-specific T-cell activation after vaccination. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and after each vaccination. T-cell activation profiles were analyzed by ELISpot assay and tested by generalized Wilcoxon for correlation to survival. | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| Median Time to Progression (TTP) | Analysis of Time to Progression and Survival Endpoints. All patients will be considered in the analysis of progression free survival time (time from start of treatment to progression or death) and survival time (time from initiation of treatment to death). Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Follow-up for this analysis will continue for all patients for their lifetimes. Time to progression and survival probabilities over time will be calculated by the method of Kaplan-Meier. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Alberto Chiappori, MD | H. Lee Moffitt Cancer Center and Research Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| H. Lee Moffitt Cancer Center and Research Institute | Tampa | Florida | 33612-9497 | United States |
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24 participants were accrued at a single center from 10/2006 to 6/2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Combination Immunotherapy | Vaccine + Cytoxan + ATRA as outlined in Detailed Description Vaccine Treatment : We created a vaccine in which irradiated allogeneic lung adenocarcinoma cells are combined with a bystander K562 cell line transfected with hCD40L and hGM-CSF. By recruiting and activating dendritic cells, we hypothesized the vaccine would induce tumor regression in metastatic lung adenocarcinoma. Intradermal vaccine was given every 14 days x3, followed by monthly x3. All-trans retinoic acid (ATRA) : All-trans retinoic acid was given (150/mg/m^2/day) after 1st and 4th vaccines to enhance dendritic differentiation. Cyclophosphamide : Cyclophosphamide (300 mg/m^2 IV) was administered before 1st and 4th vaccines to deplete regulatory T-cells. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
24 participants were accrued at a single center from 10/2006 to 6/2008. There were 14 participants with evaluable peripheral blood mononuclear cells (PBMCs).
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| ID | Title | Description |
|---|---|---|
| BG000 | Combination Immunotherapy | Vaccine + Cytoxan + ATRA as outlined in Detailed Description Vaccine Treatment : We created a vaccine in which irradiated allogeneic lung adenocarcinoma cells are combined with a bystander K562 cell line transfected with hCD40L and hGM-CSF. By recruiting and activating dendritic cells, we hypothesized the vaccine would induce tumor regression in metastatic lung adenocarcinoma. Intradermal vaccine was given every 14 days x3, followed by monthly x3. All-trans retinoic acid (ATRA) : All-trans retinoic acid was given (150/mg/m^2/day) after 1st and 4th vaccines to enhance dendritic differentiation. Cyclophosphamide : Cyclophosphamide (300 mg/m^2 IV) was administered before 1st and 4th vaccines to deplete regulatory T-cells. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Evaluable Participants With Tumor Response | Number of participants with evaluable peripheral blood mononuclear cells (PBMCs) who demonstrated sustained tumor peptide-specific T-cell activation after vaccination. Peripheral blood mononuclear cells (PBMCs) were collected at baseline and after each vaccination. T-cell activation profiles were analyzed by ELISpot assay and tested by generalized Wilcoxon for correlation to survival. | 14 participants with evaluable PBMCs | Posted | Number | participants | 3 years |
|
3 years
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Combination Immunotherapy | Vaccine + Cytoxan + ATRA as outlined in Detailed Description Vaccine Treatment : We created a vaccine in which irradiated allogeneic lung adenocarcinoma cells are combined with a bystander K562 cell line transfected with hCD40L and hGM-CSF. By recruiting and activating dendritic cells, we hypothesized the vaccine would induce tumor regression in metastatic lung adenocarcinoma. Intradermal vaccine was given every 14 days x3, followed by monthly x3. All-trans retinoic acid (ATRA) : All-trans retinoic acid was given (150/mg/m^2/day) after 1st and 4th vaccines to enhance dendritic differentiation. Cyclophosphamide : Cyclophosphamide (300 mg/m^2 IV) was administered before 1st and 4th vaccines to deplete regulatory T-cells. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE V3 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Fatigue (asthenia, lethargy, malaise) | General disorders | CTCAE V3 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alberto Chiappori, M.D. | H. Lee Moffitt Cancer Center and Research Institute | 813-745-2158 | alberto.chiappori@moffitt.org |
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| ID | Term |
|---|---|
| D008175 | Lung Neoplasms |
| D000077192 | Adenocarcinoma of Lung |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| D014212 | Tretinoin |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
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|
|
| Cyclophosphamide | Drug | Cyclophosphamide (300 mg/m^2 IV) was administered before 1st and 4th vaccines to deplete regulatory T-cells. |
|
|
| All-trans retinoic acid (ATRA) | Drug | All-trans retinoic acid was given (150/mg/m^2/day) after 1st and 4th vaccines to enhance dendritic differentiation. |
|
|
| 3 years |
| Median Overall Survival (OS) | Analysis of Time to Progression and Survival Endpoints. All patients will be considered in the analysis of progression free survival time (time from start of treatment to progression or death) and survival time (time from initiation of treatment to death). Follow-up for this analysis will continue for all patients for their lifetimes. Time to progression and survival probabilities over time will be calculated by the method of Kaplan-Meier. | 3 years |
| Number of Participants With Serious Adverse Events (SAEs) | Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Criteria (CTAE-3),Version 3.0 (www.ctep.cancer.gov). Particular attention will assess the presence of symptomatic lymphadenopathy or any local skin / soft tissue reaction at the vaccine site. Blood tests for ANA and rheumatoid factor will be performed on any patient who develops evidence of autoimmune phenomena. | 3 years |
| Participants |
|
| Age Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Median Time to Progression (TTP) | Analysis of Time to Progression and Survival Endpoints. All patients will be considered in the analysis of progression free survival time (time from start of treatment to progression or death) and survival time (time from initiation of treatment to death). Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. Follow-up for this analysis will continue for all patients for their lifetimes. Time to progression and survival probabilities over time will be calculated by the method of Kaplan-Meier. | All participants | Posted | Median | 95% Confidence Interval | months | 3 years |
|
|
|
| Secondary | Median Overall Survival (OS) | Analysis of Time to Progression and Survival Endpoints. All patients will be considered in the analysis of progression free survival time (time from start of treatment to progression or death) and survival time (time from initiation of treatment to death). Follow-up for this analysis will continue for all patients for their lifetimes. Time to progression and survival probabilities over time will be calculated by the method of Kaplan-Meier. | All participants | Posted | Median | 95% Confidence Interval | months | 3 years |
|
|
|
| Secondary | Number of Participants With Serious Adverse Events (SAEs) | Toxicity will be assessed using the NCI Common Terminology Criteria for Adverse Criteria (CTAE-3),Version 3.0 (www.ctep.cancer.gov). Particular attention will assess the presence of symptomatic lymphadenopathy or any local skin / soft tissue reaction at the vaccine site. Blood tests for ANA and rheumatoid factor will be performed on any patient who develops evidence of autoimmune phenomena. | All participants | Posted | Number | participants | 3 years |
|
|
|
| 11 |
| 24 |
| 24 |
| 24 |
| Supraventricular and nodal arrhythmia - NOS | Cardiac disorders | CTCAE V3 | Systematic Assessment |
|
| Hypotension | Cardiac disorders | CTCAE V3 | Systematic Assessment |
|
| Fatigue (asthenia, lethargy, malaise) | General disorders | CTCAE V3 | Systematic Assessment |
|
| Death not associated with CTCAE term - Disease progression - NOS | General disorders | CTCAE V3 | Systematic Assessment |
|
| Dehydration | Gastrointestinal disorders | CTCAE V3 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE V3 | Systematic Assessment |
|
| Dysphagia (difficulty swallowing) | Gastrointestinal disorders | CTCAE V3 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | CTCAE V3 | Systematic Assessment |
|
| Acidosis (metabolic or respiratory) | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
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| Albumin, serum-low (hypoalbuminemia) | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| Calcium, serum-low (hypocalcemia) | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
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| Creatinine | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| Potassium, serum-low (hypokalemia) | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| Sodium, serum-low (hyponatremia) | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| Fracture | Musculoskeletal and connective tissue disorders | CTCAE V3 | Systematic Assessment |
|
| Pain - Abdomen - NOS | General disorders | CTCAE V3 | Systematic Assessment |
|
| Pain - Kidney | Renal and urinary disorders | CTCAE V3 | Systematic Assessment |
|
| Pain - Tumor pain | General disorders | CTCAE V3 | Systematic Assessment |
|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE V3 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | CTCAE V3 | Systematic Assessment |
|
| Obstruction, GU - Ureter | Renal and urinary disorders | CTCAE V3 | Systematic Assessment |
|
| Urine color change | Renal and urinary disorders | CTCAE V3 | Systematic Assessment |
|
| Vessel injury-vein - SVC | Vascular disorders | CTCAE V3 | Systematic Assessment |
|
| Weight loss | General disorders | CTCAE V3 | Systematic Assessment |
|
| Insomnia | General disorders | CTCAE V3 | Systematic Assessment |
|
| Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 X 10^9/L) | General disorders | CTCAE V3 | Systematic Assessment |
|
| Rigors/chills | General disorders | CTCAE V3 | Systematic Assessment |
|
| Pain | General disorders | CTCAE V3 | Systematic Assessment |
|
| Pain - Head/headache | General disorders | CTCAE V3 | Systematic Assessment |
|
| Pain - joint | General disorders | CTCAE V3 | Systematic Assessment |
|
| Pain - back | General disorders | CTCAE V3 | Systematic Assessment |
|
| Pain - Abdomen - NOS | General disorders | CTCAE V3 | Systematic Assessment |
|
| Pain - Chest/thorax - NOS | General disorders | CTCAE V3 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | CTCAE V3 | Systematic Assessment |
|
| Anorexia | Gastrointestinal disorders | CTCAE V3 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE V3 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE V3 | Systematic Assessment |
|
| Dyspnea (shortness of breath) | Respiratory, thoracic and mediastinal disorders | CTCAE V3 | Systematic Assessment |
|
| Glucose, serum-high (hyperglycemia) | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| Alkaline phosphatase | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| Creatinine | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| Metabolic/Laboratory - other | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| ALT, SGPT (serum glutamic pyruvic transaminase) | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| AST, SGOT (serum glutamic oxaloacetic transaminase) | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| Potassium, serum-high (hyperkalemia) | Metabolism and nutrition disorders | CTCAE V3 | Systematic Assessment |
|
| Injection site reaction/extravasation changes | Skin and subcutaneous tissue disorders | CTCAE V3 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | CTCAE V3 | Systematic Assessment |
|
| Rash: acne/acneiform | Skin and subcutaneous tissue disorders | CTCAE V3 | Systematic Assessment |
|
| Hemoglobin | Blood and lymphatic system disorders | CTCAE V3 | Systematic Assessment |
|
| Platelets | Blood and lymphatic system disorders | CTCAE V3 | Systematic Assessment |
|
| Allergic rhinitis | Immune system disorders | CTCAE V3 | Systematic Assessment |
|
| Allergy/Immunology - other | Immune system disorders | CTCAE V3 | Systematic Assessment |
|
| Mood alteration - Anxiety | General disorders | CTCAE V3 | Systematic Assessment |
|
| Neuropathy: sensory | Nervous system disorders | CTCAE V3 | Systematic Assessment |
|
| Hypertension | Cardiac disorders | CTCAE V3 | Systematic Assessment |
|
| Musculoskeletal/Soft - other | Musculoskeletal and connective tissue disorders | CTCAE V3 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | CTCAE V3 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE V3 | Systematic Assessment |
|
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| D008171 |
| Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D014801 | Vitamin A |
| D012176 | Retinoids |
| D002338 | Carotenoids |
| D011090 | Polyenes |
| D000475 | Alkenes |
| D006839 | Hydrocarbons, Acyclic |
| D053138 | Cyclohexenes |
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D013729 | Terpenes |
| D004224 | Diterpenes |
| D010860 | Pigments, Biological |
| D001685 | Biological Factors |