Vaccine Therapy in Treating Patients With Transitional Cell Carcinomas

NCT ID: NCT00070070

Last Updated: 2022-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-10-28
• Study Completion Date: 2013-09-30

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.

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.

Conditions

Transitional Cell Carcinoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

TICE®-strain BCG

Intervention Type: BIOLOGICAL

NY-ESO-1 protein

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

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.

Group Type: EXPERIMENTAL

TICE®-strain BCG

Intervention Type: BIOLOGICAL

NY-ESO-1 protein

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

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.

Group Type: EXPERIMENTAL

TICE®-strain BCG

Intervention Type: BIOLOGICAL

NY-ESO-1 protein

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

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.

Group Type: EXPERIMENTAL

TICE®-strain BCG

Intervention Type: BIOLOGICAL

NY-ESO-1 protein

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

Interventions

TICE®-strain BCG

Intervention Type: BIOLOGICAL

NY-ESO-1 protein

Intervention Type: BIOLOGICAL

sargramostim

Intervention Type: BIOLOGICAL

Other Intervention Names

BCG Live; Tice® BCG; BCG Vaccine; GM-CSF

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Ludwig Institute for Cancer Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dean F. Bajorin, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Harry W. Herr, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Countries

United States

References

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.0b013e3181891574.

Reference Type: RESULT

PMID: 18833002 (View on PubMed)

Other Identifiers

MSKCC-03047

Identifier Type: OTHER

Identifier Source: secondary_id

LUDWIG-LUD2002-004

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000329920

Identifier Type: OTHER

Identifier Source: secondary_id

LUD2002-004

Identifier Type: -

Identifier Source: org_study_id