Vaccine Therapy in Treating Patients With Transitional Cell Carcinomas

• Sponsor: Ludwig Institute for Cancer Research (Other)
• Overall Status: Completed
• CT.gov ID: NCT00070070
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 6
• Location: 1
• Arms: 4
• Actual Duration (Months): 119.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells. Biological therapies, such as Bacille Calmette Guerin (BCG) and sargramostim (GM-CSF), use different ways to stimulate the immune system and stop tumor cells from growing. Combining vaccine therapy with biological therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects of giving vaccine therapy together with BCG and sargramostim in treating patients who have undergone cystectomy for transitional cell carcinomas.

Condition or Disease	Intervention/Treatment	Phase
Transitional Cell Carcinoma	Biological: TICE®-strain BCG; Biological: NY-ESO-1 protein; Biological: sargramostim	Phase 1

Detailed Description

OBJECTIVES:

• Determine the safety and tolerability of NY-ESO-1 peptide vaccine, Bacille Calmette Guerin (BCG), and sargramostim (GM-CSF) in post-cystectomy patients with transitional cell carcinoma of the bladder expressing NY-ESO-1 or LAGE-1 antigen.

• Determine the immunological profile (NY-ESO-1 antibody, CD8+ cells, and delayed-type hypersensitivity) induced by this regimen in these patients.

OUTLINE: This is an open-label, pilot study.

Patients receive NY-ESO-1 protein vaccine mixed with BCG intradermally (ID) once weekly on weeks 1 and 2. Patients then receive NY-ESO-1 protein mixed with sargramostim (GM-CSF) ID once weekly on day 2 of weeks 3-6. Patients also receive GM-CSF subcutaneously alone on days 1, 3, 4, and 5 of weeks 3-6.

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: This study was open-label, and eligible patients were sequentially entered at the time they presented in clinic. Patients were sequentially assigned to one of four groups according to HLA-A2 characteristic and previous Bacille Calmette Guerin (BCG) therapy.This study was open-label, and eligible patients were sequentially entered at the time they presented in clinic. Patients were sequentially assigned to one of four groups according to HLA-A2 characteristic and previous Bacille Calmette Guerin (BCG) therapy.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: NY-ESO-1 Protein Immunization of Post-Cystectomy or Post-Nephroureterectomy Patients With Transitional Cell Carcinomas
• Actual Study Start Date: Oct 28, 2003
• Actual Primary Completion Date: Jan 3, 2006
• Actual Study Completion Date: Sep 30, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort 1 HLA-A2 Status Positive, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	Biological: TICE®-strain BCG; Other Names: BCG Live Tice® BCG BCG Vaccine ; Biological: NY-ESO-1 protein; Biological: sargramostim; Other Names: GM-CSF
Experimental: Cohort 2 HLA-A2 Status Positive, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	Biological: TICE®-strain BCG; Other Names: BCG Live Tice® BCG BCG Vaccine ; Biological: NY-ESO-1 protein; Biological: sargramostim; Other Names: GM-CSF
Experimental: Cohort 3 HLA-A2 Status Negative, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	Biological: TICE®-strain BCG; Other Names: BCG Live Tice® BCG BCG Vaccine ; Biological: NY-ESO-1 protein; Biological: sargramostim; Other Names: GM-CSF
Experimental: Cohort 4 HLA-A2 Status Negative, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 106 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 105 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	Biological: TICE®-strain BCG; Other Names: BCG Live Tice® BCG BCG Vaccine ; Biological: NY-ESO-1 protein; Biological: sargramostim; Other Names: GM-CSF

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicities [up to 12 weeks]

   All adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTCAE) (Version 3.0). A Dose limiting toxicity (DLT) was defined as: ≥ Grade 2 autoimmune phenomena Asymptomatic bronchospasm or generalized urticaria ≥ Grade 3 hematological and non hematological toxicities. To be dose limiting, an adverse event must have been definitely, probably, or possibly related to the administration of the study treatment. Patients who experienced a DLT were removed from study.

Secondary Outcome Measures

1. Number of Patients Developing NY-ESO-1 Antibodies After Treatment [up to 12 weeks]

   Blood samples were obtained at baseline, and at weeks 2, 4, 6, 8 and 12 for the assessment of NY-ESO-1 and LAGE-1 specific antibodies by enzyme-linked immunosorbent assay (ELISA).

2. Number of Patients With CD4+ and CD8+ T-cell Responses. [up to 12 weeks]

   Blood samples were obtained at baseline, and at weeks 2, 4, 6, 8 and 12 for the assessment of NY-ESO-1 specific T-cell responses by ELISPOT. T-cell responses were monitored after in vitro sensitization with either overlapping peptides from NY-ESO-1 or recombinant adenovirus encoding NY-ESO-1 (adeno-NY-ESO-1), and with control peptides or recombinant vectors encoding Influenza-derived proteins.

3. Delayed-type Hypersensitivity (DTH) as Measured by the Number of Participants With Induration and/or Redness at Each Timepoint [up to 8 weeks]

   NY-ESO-1-specific DTH skin reaction was measured at baseline and weeks 3 and 8.The peptide solution (10 μg peptide in 0.1ml normal saline) was injected intradermally at a separate site from the vaccination to give a visible and palpable skin depot. Assessment of DTH reactions was performed 48 h after injection. The extent and intensity of DTH reactions was documented by measuring visible "redness", palpable "induration" and other signs of local skin irritation or necrosis.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria

1. Post-cystectomy or post-nephroureterectomy patients with histological confirmation of transitional cell carcinoma.

2. Patients must have had a cystectomy or nephroureterectomy within 16 weeks of first vaccination.

3. At least 4 weeks since surgery prior to receiving the first vaccination.

4. Radiological imaging to document no evidence of disease within one month prior to receiving the first vaccination.

5. Laboratory values within the following limits:

Hemoglobin ≥ 10.0 g/dL Neutrophil count ≥ 1.5 x 10E9/L Lymphocyte count ≥ 0.5 x 10E9/L Platelet count ≥ 100 x 10E9/L Serum creatinine ≤ 1.8 mg/dL Serum bilirubin ≤ 2mg/dL Serum aspartate aminotransferase (AST) (SGOT) <2.5 X ULN Serum alanine aminotransaminase (ALT) (SGPT) <2.5 X ULN 6. Performance status ≤ 2 (ECOG Scale) and life expectancy ≥ 3 months. 7. Age ≥ 18 years. 8. Fertile patients must have a negative urine or serum pregnancy test and use barrier method contraception before, during and for 6 months after protocol therapy. Patients are encouraged to continue barrier method contraception for two years or longer after treatment.

1. Able and willing to give valid written informed consent. Exclusion Criteria

2. Clinically significant heart disease (NYHA Class III or IV).

3. Presence of severe reaction to PPD (purified protein derivative) (>40 mm induration).

4. Prior malignancy within 5 years that has been treated with extensive chemotherapy / radiation therapy and have the potential for immune dysfunction or who have evidence of metastasis at the time of registration.

5. Other serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders, antibiotic use within 5 days of treatment.

6. Previous bone marrow or stem cell transplant.

7. History of immunodeficiency disease or autoimmune disease.

8. Known positive HIV test.

9. Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).

10. Concomitant treatment with corticosteroids (within 30 days of enrollment and during treatment), antihistaminic drugs, or nonsteroidal anti-inflammatory drugs (unless chronically used in low doses for prevention of an acute cardiovascular event or pain control). Topical or inhalational steroids are permitted.

11. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.

12. Mental disorders that may compromise the ability to give informed consent and comply with the requirements of the study.

13. Lack of availability of the patient for immunological and clinical follow-up assessment.

14. Positive urine or serum pregnancy test.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021

Sponsors and Collaborators

• Ludwig Institute for Cancer Research
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Dean F. Bajorin, MD, Memorial Sloan Kettering Cancer Center
• Principal Investigator: Harry W. Herr, MD, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ludwig Institute for Cancer Research
• ClinicalTrials.gov Identifier: NCT00070070
• Other Study ID Numbers: LUD2002-004; MSKCC-03047; LUDWIG-LUD2002-004; CDR0000329920
• First Posted: Oct 7, 2003
• Last Update Posted: Jul 12, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Ludwig Institute for Cancer Research: Bladder cancer; Renal pelvis cancer
• Additional relevant MeSH terms: Carcinoma; Carcinoma, Transitional Cell; Sargramostim; BCG Vaccine

Study Results

Participant Flow

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Arm/Group Description	HLA-A2 Status Positive, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Positive, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.
Period Title: Overall Study
STARTED	1	0	0	5
COMPLETED	1	0	0	5
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4	Total
Arm/Group Description	HLA-A2 Status Positive, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Positive, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	Total of all reporting groups
Overall Participants	1	0	0	5	6
Age (Count of Participants)
<=18 years	0 0%	0 NaN	0 NaN	0 0%	0 0%
Between 18 and 65 years	1 100%	0 NaN	0 NaN	0 0%	1 16.7%
>=65 years	0 0%	0 NaN	0 NaN	5 100%	5 83.3%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 NaN	0 NaN	1 20%	1 16.7%
Male	1 100%	0 NaN	0 NaN	4 80%	5 83.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 NaN	0 NaN	0 0%	0 0%
Not Hispanic or Latino	1 100%	0 NaN	0 NaN	5 100%	6 100%
Unknown or Not Reported	0 0%	0 NaN	0 NaN	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 NaN	0 NaN	0 0%	0 0%
Asian	0 0%	0 NaN	0 NaN	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 NaN	0 NaN	0 0%	0 0%
Black or African American	0 0%	0 NaN	0 NaN	0 0%	0 0%
White	1 100%	0 NaN	0 NaN	5 100%	6 100%
More than one race	0 0%	0 NaN	0 NaN	0 0%	0 0%
Unknown or Not Reported	0 0%	0 NaN	0 NaN	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	1 100%	5 Infinity	6 Infinity

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities
Description	All adverse events were graded according to the National Cancer Institute Common Toxicity Criteria (CTCAE) (Version 3.0). A Dose limiting toxicity (DLT) was defined as: ≥ Grade 2 autoimmune phenomena Asymptomatic bronchospasm or generalized urticaria ≥ Grade 3 hematological and non hematological toxicities. To be dose limiting, an adverse event must have been definitely, probably, or possibly related to the administration of the study treatment. Patients who experienced a DLT were removed from study.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one study treatment. One participant in Cohort 4 did not have HLA-A2 status tested.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Arm/Group Description	HLA-A2 Status Positive, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Positive, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.
Measure Participants	1	0	0	5
Count of Participants [Participants]	0 0%	0 NaN	0 NaN	0 0%

2. Secondary Outcome

Title	Number of Patients Developing NY-ESO-1 Antibodies After Treatment
Description	Blood samples were obtained at baseline, and at weeks 2, 4, 6, 8 and 12 for the assessment of NY-ESO-1 and LAGE-1 specific antibodies by enzyme-linked immunosorbent assay (ELISA).
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

All participants who received study therapy and had blood samples taken for antibody analysis before and after treatment. One participant in Cohort 4 did not have HLA-A2 status tested.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Arm/Group Description	HLA-A2 Status Positive, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Positive, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.
Measure Participants	1	0	0	5
Number of Participants with NY-ESO-1 Antibodies at Baseline and After Treatment	1 100%	0 NaN	0 NaN	0 0%
Number of Participants with No NY-ESO-1 Antibodies at Baseline and Antibodies After Treatment	0 0%	0 NaN	0 NaN	4 80%
Number of Participants with No NY-ESO-1 Antibodies at Baseline and No Antibodies After Treatment	0 0%	0 NaN	0 NaN	1 20%

3. Secondary Outcome

Title	Number of Patients With CD4+ and CD8+ T-cell Responses.
Description	Blood samples were obtained at baseline, and at weeks 2, 4, 6, 8 and 12 for the assessment of NY-ESO-1 specific T-cell responses by ELISPOT. T-cell responses were monitored after in vitro sensitization with either overlapping peptides from NY-ESO-1 or recombinant adenovirus encoding NY-ESO-1 (adeno-NY-ESO-1), and with control peptides or recombinant vectors encoding Influenza-derived proteins.
Time Frame	up to 12 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study therapy and had pre- and post-treatment samples taken for analysis. One participant in Cohort 4 did not have HLA-A2 status tested.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Arm/Group Description	HLA-A2 Status Positive, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Positive, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.
Measure Participants	1	0	0	5
Number of Participants with Responses	1 100%	0 NaN	0 NaN	5 100%
Number of Participants without Responses	0 0%	0 NaN	0 NaN	0 0%
Number of Participants with Responses	0 0%	0 NaN	0 NaN	1 20%
Number of Participants without Responses	1 100%	0 NaN	0 NaN	4 80%

4. Secondary Outcome

Title	Delayed-type Hypersensitivity (DTH) as Measured by the Number of Participants With Induration and/or Redness at Each Timepoint
Description	NY-ESO-1-specific DTH skin reaction was measured at baseline and weeks 3 and 8.The peptide solution (10 μg peptide in 0.1ml normal saline) was injected intradermally at a separate site from the vaccination to give a visible and palpable skin depot. Assessment of DTH reactions was performed 48 h after injection. The extent and intensity of DTH reactions was documented by measuring visible "redness", palpable "induration" and other signs of local skin irritation or necrosis.
Time Frame	up to 8 weeks

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study treatment and received the DTH test at the respective timepoint. One participant in Cohort 4 did not have HLA-A2 status tested.

Arm/Group Title	Cohort 1	Cohort 2	Cohort 3	Cohort 4
Arm/Group Description	HLA-A2 Status Positive, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Positive, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.	HLA-A2 Status Negative, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.
Measure Participants	1	0	0	5
Number of Participants with Induration and/or Redness	0 0%	0 NaN	0 NaN	2 40%
Number of Participants with No Induration and/or Redness	1 100%	0 NaN	0 NaN	3 60%
Number of Participants with Induration and/or Redness	0 0%	0 NaN	0 NaN	2 40%
Number of Participants with No Induration and/or Redness	1 100%	0 NaN	0 NaN	2 40%
Number of Participants with Induration and/or Redness	0 0%	0 NaN	0 NaN	1 20%
Number of Participants with No Induration and/or Redness	1 100%	0 NaN	0 NaN	3 60%

Adverse Events

Time Frame	up to 12 weeks
Adverse Event Reporting Description	All AEs occurring during the study were to be documented in the source records and on the respective Case Report Form Adverse Event page, regardless of the assumption of a causal relationship. All events, which occurred after signed informed consent, were to be documented. Toxicity was evaluated according to the National Cancer Institute CTCAE Version 3.0.
Arm/Group Title	Cohort 1		Cohort 2		Cohort 3		Cohort 4
Arm/Group Description	HLA-A2 Status Positive, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.		HLA-A2 Status Positive, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.		HLA-A2 Status Negative, Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.		HLA-A2 Status Negative, No Previous BCG Therapy; All patients underwent skin testing with the purified protein derivative (PPD) test. NY-ESO-1 protein, 75 mcg, was administered by intradermal injection every week for 6 weeks. TICE®-strain BCG, 1 x 10E6 viable units in Purified Protein Derivative (PPD) negative patients and 1 x 10E5 viable units in PPD positive (induration greater than or equal to 10 mm) patients, were mixed with each protein vaccination for the first 2 weeks only. For the last 4 weeks GM-CSF, 100 mcg, was mixed with NY-ESO-1 protein given once a week for 4 weeks, intradermally. GM-CSF alone was given subcutaneously on the day prior to the administration of the co-mixture (NY-ESO-1 Protein/GM-CSF) and for 3 days after.
All Cause Mortality
	Cohort 1		Cohort 2		Cohort 3		Cohort 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)		0/0 (NaN)		0/5 (0%)
Serious Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/1 (0%)		0/0 (NaN)		0/0 (NaN)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1		Cohort 2		Cohort 3		Cohort 4
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100%)		0/0 (NaN)		0/0 (NaN)		5/5 (100%)
Cardiac disorders
Peripheral edema	0/1 (0%)		0/0 (NaN)		0/0 (NaN)		1/5 (20%)
Gastrointestinal disorders
Gastroesophageal reflux disease	1/1 (100%)		0/0 (NaN)		0/0 (NaN)		0/5 (0%)
General disorders
Fatigue	0/1 (0%)		0/0 (NaN)		0/0 (NaN)		2/5 (40%)
Injection site reaction	1/1 (100%)		0/0 (NaN)		0/0 (NaN)		5/5 (100%)
Investigations
Blood calcium decreased	0/1 (0%)		0/0 (NaN)		0/0 (NaN)		1/5 (20%)
Reproductive system and breast disorders
Perineal pain	0/1 (0%)		0/0 (NaN)		0/0 (NaN)		1/5 (20%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/1 (0%)		0/0 (NaN)		0/0 (NaN)		1/5 (20%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.