Trial Outcomes & Findings for Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer (NCT NCT00601796)
NCT ID: NCT00601796
Last Updated: 2013-05-24
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
24 participants
Primary outcome timeframe
3 years
Results posted on
2013-05-24
Participant Flow
24 participants were accrued at a single center from 10/2006 to 6/2008.
Participant milestones
| Measure |
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.
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|---|---|
|
Overall Study
STARTED
|
24
|
|
Overall Study
COMPLETED
|
24
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Vaccine Therapy, Tretinoin, and Cyclophosphamide in Treating Patients With Metastatic Lung Cancer
Baseline characteristics by cohort
| Measure |
Combination Immunotherapy
n=24 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
12 Participants
n=5 Participants
|
|
Age Continuous
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 yearsPopulation: 14 participants with evaluable PBMCs
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.
Outcome measures
| Measure |
Combination Immunotherapy
n=14 Participants
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.
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|---|---|
|
Number of Evaluable Participants With Tumor Response
|
5 participants
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: All participants
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.
Outcome measures
| Measure |
Combination Immunotherapy
n=24 Participants
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.
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|---|---|
|
Median Time to Progression (TTP)
|
2.4 months
Interval 0.3 to 4.6
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: All participants
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.
Outcome measures
| Measure |
Combination Immunotherapy
n=24 Participants
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.
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|---|---|
|
Median Overall Survival (OS)
|
8 months
Interval 3.5 to 12.5
|
SECONDARY outcome
Timeframe: 3 yearsPopulation: All participants
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.
Outcome measures
| Measure |
Combination Immunotherapy
n=24 Participants
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.
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|---|---|
|
Number of Participants With Serious Adverse Events (SAEs)
|
11 participants
|
Adverse Events
Combination Immunotherapy
Serious events: 11 serious events
Other events: 24 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Combination Immunotherapy
n=24 participants at risk
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.
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|---|---|
|
Blood and lymphatic system disorders
Hemoglobin
|
4.2%
1/24 • Number of events 3 • 3 years
|
|
Cardiac disorders
Supraventricular and nodal arrhythmia - NOS
|
4.2%
1/24 • Number of events 1 • 3 years
|
|
Cardiac disorders
Hypotension
|
4.2%
1/24 • Number of events 3 • 3 years
|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
4.2%
1/24 • Number of events 2 • 3 years
|
|
General disorders
Death not associated with CTCAE term - Disease progression - NOS
|
4.2%
1/24 • Number of events 1 • 3 years
|
|
Gastrointestinal disorders
Dehydration
|
4.2%
1/24 • Number of events 2 • 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
4.2%
1/24 • Number of events 1 • 3 years
|
|
Gastrointestinal disorders
Dysphagia (difficulty swallowing)
|
4.2%
1/24 • Number of events 2 • 3 years
|
|
Gastrointestinal disorders
Nausea
|
4.2%
1/24 • Number of events 1 • 3 years
|
|
Metabolism and nutrition disorders
Acidosis (metabolic or respiratory)
|
4.2%
1/24 • Number of events 1 • 3 years
|
|
Metabolism and nutrition disorders
Albumin, serum-low (hypoalbuminemia)
|
4.2%
1/24 • Number of events 2 • 3 years
|
|
Metabolism and nutrition disorders
Calcium, serum-low (hypocalcemia)
|
4.2%
1/24 • Number of events 2 • 3 years
|
|
Metabolism and nutrition disorders
Creatinine
|
4.2%
1/24 • Number of events 2 • 3 years
|
|
Metabolism and nutrition disorders
Potassium, serum-low (hypokalemia)
|
4.2%
1/24 • Number of events 2 • 3 years
|
|
Metabolism and nutrition disorders
Sodium, serum-low (hyponatremia)
|
4.2%
1/24 • Number of events 1 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Fracture
|
4.2%
1/24 • Number of events 1 • 3 years
|
|
General disorders
Pain - Abdomen - NOS
|
4.2%
1/24 • Number of events 2 • 3 years
|
|
Renal and urinary disorders
Pain - Kidney
|
4.2%
1/24 • Number of events 1 • 3 years
|
|
General disorders
Pain - Tumor pain
|
8.3%
2/24 • Number of events 3 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
12.5%
3/24 • Number of events 5 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
8.3%
2/24 • Number of events 3 • 3 years
|
|
Renal and urinary disorders
Obstruction, GU - Ureter
|
4.2%
1/24 • Number of events 1 • 3 years
|
|
Renal and urinary disorders
Urine color change
|
4.2%
1/24 • Number of events 1 • 3 years
|
|
Vascular disorders
Vessel injury-vein - SVC
|
4.2%
1/24 • Number of events 1 • 3 years
|
Other adverse events
| Measure |
Combination Immunotherapy
n=24 participants at risk
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.
|
|---|---|
|
General disorders
Fatigue (asthenia, lethargy, malaise)
|
79.2%
19/24 • Number of events 26 • 3 years
|
|
General disorders
Weight loss
|
20.8%
5/24 • Number of events 5 • 3 years
|
|
General disorders
Insomnia
|
16.7%
4/24 • Number of events 4 • 3 years
|
|
General disorders
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 X 10^9/L)
|
8.3%
2/24 • Number of events 2 • 3 years
|
|
General disorders
Rigors/chills
|
8.3%
2/24 • Number of events 2 • 3 years
|
|
General disorders
Pain
|
79.2%
19/24 • Number of events 44 • 3 years
|
|
General disorders
Pain - Head/headache
|
58.3%
14/24 • Number of events 18 • 3 years
|
|
General disorders
Pain - joint
|
25.0%
6/24 • Number of events 8 • 3 years
|
|
General disorders
Pain - back
|
20.8%
5/24 • Number of events 5 • 3 years
|
|
General disorders
Pain - Abdomen - NOS
|
12.5%
3/24 • Number of events 3 • 3 years
|
|
General disorders
Pain - Chest/thorax - NOS
|
12.5%
3/24 • Number of events 3 • 3 years
|
|
Gastrointestinal disorders
Nausea
|
41.7%
10/24 • Number of events 14 • 3 years
|
|
Gastrointestinal disorders
Anorexia
|
37.5%
9/24 • Number of events 11 • 3 years
|
|
Gastrointestinal disorders
Constipation
|
29.2%
7/24 • Number of events 8 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
50.0%
12/24 • Number of events 15 • 3 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea (shortness of breath)
|
41.7%
10/24 • Number of events 11 • 3 years
|
|
Metabolism and nutrition disorders
Glucose, serum-high (hyperglycemia)
|
37.5%
9/24 • Number of events 9 • 3 years
|
|
Metabolism and nutrition disorders
Alkaline phosphatase
|
25.0%
6/24 • Number of events 9 • 3 years
|
|
Metabolism and nutrition disorders
Creatinine
|
25.0%
6/24 • Number of events 7 • 3 years
|
|
Metabolism and nutrition disorders
Metabolic/Laboratory - other
|
12.5%
3/24 • Number of events 3 • 3 years
|
|
Metabolism and nutrition disorders
ALT, SGPT (serum glutamic pyruvic transaminase)
|
8.3%
2/24 • Number of events 2 • 3 years
|
|
Metabolism and nutrition disorders
AST, SGOT (serum glutamic oxaloacetic transaminase)
|
8.3%
2/24 • Number of events 2 • 3 years
|
|
Metabolism and nutrition disorders
Potassium, serum-high (hyperkalemia)
|
8.3%
2/24 • Number of events 2 • 3 years
|
|
Skin and subcutaneous tissue disorders
Injection site reaction/extravasation changes
|
33.3%
8/24 • Number of events 9 • 3 years
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
20.8%
5/24 • Number of events 6 • 3 years
|
|
Skin and subcutaneous tissue disorders
Rash: acne/acneiform
|
12.5%
3/24 • Number of events 3 • 3 years
|
|
Blood and lymphatic system disorders
Hemoglobin
|
37.5%
9/24 • Number of events 13 • 3 years
|
|
Blood and lymphatic system disorders
Platelets
|
8.3%
2/24 • Number of events 3 • 3 years
|
|
Immune system disorders
Allergic rhinitis
|
20.8%
5/24 • Number of events 5 • 3 years
|
|
Immune system disorders
Allergy/Immunology - other
|
16.7%
4/24 • Number of events 4 • 3 years
|
|
General disorders
Mood alteration - Anxiety
|
12.5%
3/24 • Number of events 4 • 3 years
|
|
Nervous system disorders
Neuropathy: sensory
|
8.3%
2/24 • Number of events 2 • 3 years
|
|
Cardiac disorders
Hypertension
|
12.5%
3/24 • Number of events 3 • 3 years
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal/Soft - other
|
12.5%
3/24 • Number of events 3 • 3 years
|
|
Gastrointestinal disorders
Vomiting
|
16.7%
4/24 • Number of events 5 • 3 years
|
|
Gastrointestinal disorders
Diarrhea
|
12.5%
3/24 • Number of events 4 • 3 years
|
Additional Information
Alberto Chiappori, M.D.
H. Lee Moffitt Cancer Center and Research Institute
Phone: 813-745-2158
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place