Vaccine Therapy in Treating Patients With Transitional Cell Carcinomas

Transitional Cell Carcinoma Clinical Trial

Official title:

NY-ESO-1 Protein Immunization of Post-Cystectomy or Post-Nephroureterectomy Patients With Transitional Cell Carcinomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00070070
• Other study ID #: LUD2002-004
• Secondary ID: MSKCC-03047LUDWI
• Status: Completed
• Phase: Phase 1
• Start date: October 28, 2003
• Est. completion date: September 30, 2013

Study information

• Verified date: October 2022
• Source: Ludwig Institute for Cancer Research
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: September 30, 2013
• Est. primary completion date: January 3, 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

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

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

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

3. 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.

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

5. Previous bone marrow or stem cell transplant.

6. History of immunodeficiency disease or autoimmune disease.

7. Known positive HIV test.

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

9. 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.

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

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

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

13. Positive urine or serum pregnancy test.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Transitional Cell
• Transitional Cell Carcinoma

Intervention

Biological:
• TICE®-strain BCG

• NY-ESO-1 protein

• sargramostim

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Ludwig Institute for Cancer Research	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Sharma P, Bajorin DF, Jungbluth AA, Herr H, Old LJ, Gnjatic S. Immune responses detected in urothelial carcinoma patients after vaccination with NY-ESO-1 protein plus BCG and GM-CSF. J Immunother. 2008 Nov-Dec;31(9):849-57. doi: 10.1097/CJI.0b013e31818915 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Dose Limiting Toxicities	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.	up to 12 weeks
Secondary	Number of Patients Developing NY-ESO-1 Antibodies After Treatment	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).	up to 12 weeks
Secondary	Number of Patients With CD4+ and CD8+ T-cell Responses.	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.	up to 12 weeks
Secondary	Delayed-type Hypersensitivity (DTH) as Measured by the Number of Participants With Induration and/or Redness at Each Timepoint	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.	up to 8 weeks