NCT00070070

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Oct 2003

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 3, 2003

Completed
4 days until next milestone

First Posted

Study publicly available on registry

October 7, 2003

Completed
21 days until next milestone

Study Start

First participant enrolled

October 28, 2003

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 3, 2006

Completed
7.7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 30, 2013

Completed
7.8 years until next milestone

Results Posted

Study results publicly available

July 8, 2021

Completed
Last Updated

October 12, 2022

Status Verified

October 1, 2022

Enrollment Period

2.2 years

First QC Date

October 3, 2003

Results QC Date

June 15, 2021

Last Update Submit

October 3, 2022

Conditions

Keywords

Bladder cancerRenal pelvis cancer

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (3)

  • Number of Patients Developing NY-ESO-1 Antibodies After Treatment

    up to 12 weeks

  • Number of Patients With CD4+ and CD8+ T-cell Responses.

    up to 12 weeks

  • Delayed-type Hypersensitivity (DTH) as Measured by the Number of Participants With Induration and/or Redness at Each Timepoint

    up to 8 weeks

Study Arms (4)

Cohort 1

EXPERIMENTAL

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 BCGBiological: NY-ESO-1 proteinBiological: sargramostim

Cohort 2

EXPERIMENTAL

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 BCGBiological: NY-ESO-1 proteinBiological: sargramostim

Cohort 3

EXPERIMENTAL

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 BCGBiological: NY-ESO-1 proteinBiological: sargramostim

Cohort 4

EXPERIMENTAL

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 BCGBiological: NY-ESO-1 proteinBiological: sargramostim

Interventions

Also known as: BCG Live, Tice® BCG, BCG Vaccine
Cohort 1Cohort 2Cohort 3Cohort 4
Cohort 1Cohort 2Cohort 3Cohort 4
sargramostimBIOLOGICAL
Also known as: GM-CSF
Cohort 1Cohort 2Cohort 3Cohort 4

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Post-cystectomy or post-nephroureterectomy patients with histological confirmation of transitional cell carcinoma.
  • Patients must have had a cystectomy or nephroureterectomy within 16 weeks of first vaccination.
  • At least 4 weeks since surgery prior to receiving the first vaccination.
  • Radiological imaging to document no evidence of disease within one month prior to receiving the first vaccination.
  • 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.

You may not qualify if:

  • Clinically significant heart disease (NYHA Class III or IV).
  • Presence of severe reaction to PPD (purified protein derivative) (\>40 mm induration).
  • 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.
  • Other serious illnesses, e.g., serious infections requiring antibiotics, bleeding disorders, antibiotic use within 5 days of treatment.
  • Previous bone marrow or stem cell transplant.
  • History of immunodeficiency disease or autoimmune disease.
  • Known positive HIV test.
  • Chemotherapy, radiation therapy, or immunotherapy within 4 weeks before study entry (6 weeks for nitrosoureas).
  • 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.
  • Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
  • Mental disorders that may compromise the ability to give informed consent and comply with the requirements of the study.
  • Lack of availability of the patient for immunological and clinical follow-up assessment.
  • Positive urine or serum pregnancy test.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Related 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.0b013e3181891574.

MeSH Terms

Conditions

Carcinoma, Transitional CellUrinary Bladder Neoplasms

Interventions

BCG VaccinesargramostimGranulocyte-Macrophage Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

CarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsUrologic NeoplasmsUrogenital NeoplasmsNeoplasms by SiteFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Tuberculosis VaccinesBacterial VaccinesVaccinesBiological ProductsComplex MixturesColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Results Point of Contact

Title
Jonathan Skipper PhD
Organization
Ludwig Institute for Cancer Research

Study Officials

  • Dean F. Bajorin, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR
  • Harry W. Herr, MD

    Memorial Sloan Kettering Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 3, 2003

First Posted

October 7, 2003

Study Start

October 28, 2003

Primary Completion

January 3, 2006

Study Completion

September 30, 2013

Last Updated

October 12, 2022

Results First Posted

July 8, 2021

Record last verified: 2022-10

Data Sharing

IPD Sharing
Will not share

Locations