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Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma

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ClinicalTrials.gov Identifier: NCT00019682
Recruitment Status : Completed
First Posted : January 27, 2003
Results First Posted : November 20, 2017
Last Update Posted : November 20, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Tracking Information
First Submitted Date  ICMJE July 11, 2001
First Posted Date  ICMJE January 27, 2003
Results First Submitted Date  ICMJE December 2, 2016
Results First Posted Date  ICMJE November 20, 2017
Last Update Posted Date November 20, 2017
Study Start Date  ICMJE December 1999
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 16, 2017)
Best Response Rate (Partial Response [PR] + Complete Response [CR]) [ Time Frame: Up to 12 years ]
A complete response (CR) was defined as the disappearance of all clinical evidence of disease for at least 4 weeks. A partial response (PR) was defined as a 50% or greater decrease in the sum of the products of perpendicular diameters of all measurable lesions for at least one month. No new lesions could appear, and none could increase 25% or more.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00019682 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 16, 2017)
  • Progression Free Survival [ Time Frame: From the date of randomization until documentation of progression or last follow up, assessed up to 12 years ]
    Progression free survival was compared between groups by means of Kaplan-Meier curves using the log-rank test to evaluate the significance of the difference between the arms.
  • Change in T-cell Precursors [ Time Frame: Baseline to up to 12 years ]
    To measure change in T-cell precursors, PBMC were tested for reactivity by measuring gamma-interferon release after overnight coculture with peptide pulsed T2 cells. PBMC obtained after 4 cycles of study treatment were compared to pre treatment PBMC. A positive assay was defined as greater than 100pg/ml gamma-interferon release and at least twice the release (including all control peptides) by post treatment PBMC compared to pre treatment PBMC.
  • Change in Quality of Life (QOL) Score Assessed by the FACT-G (Functional Assessment of Cancer Therapy- General), FACT-F (Functional Assessment of Cancer Therapy- Fatigue), SF-36 (Short Form 36) and SDS (Symptom Distress Scale) [ Time Frame: Baseline to up to 8 weeks ]
    QOL was measured before and after 2 cycles of treatment using 4 measures: FACT-G is a 27 item measure of QOL. A total score is calculated by summing across responses on a 5 point scale and ranges from 0-135, with higher scores indicating better QOL. FACT-F is 13 item measure of fatigue. A total score is calculated by summing across responses on a 5 point scale. Total score ranges from 0-52, with higher scores indicating less fatigue. SF-36 is a 36 item measure of self-reported health status. SF-36 is comprised of 8 subscales: physical function, role physical, bodily pain vitality, role emotional function, mental health, social function and general health. Summated scores range from 0-100, with higher scores indicating a better health state. SDS is a 13 item measure of symptom distress. A total score is calculated by summing across responses on a 5 point scale. Total score ranges from 13 to 65, with higher scores indicating more symptom distress.
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Aldesleukin With or Without Vaccine Therapy in Treating Patients With Locally Advanced or Metastatic Melanoma
Official Title  ICMJE A Phase III Multi-Institutional Randomized Study of Immunization With the gp100: 209-217 (210M) Peptide Followed by High Dose IL-2 vs. High Dose IL-2 Alone in Patients With Metastatic Melanoma
Brief Summary This randomized phase III trial studies aldesleukin with vaccine therapy to see how well it works compared to aldesleukin alone in treating patients with melanoma that has spread from where it started to nearby tissue or lymph nodes or to other places in the body. Aldesleukin may stimulate a person's white blood cells to kill melanoma cells. Vaccines may make the body build an immune response to kill tumor cells. It is not yet known whether combining aldesleukin with vaccine therapy is more effective than aldesleukin alone in treating melanoma.
Detailed Description

PRIMARY OBJECTIVES:

I. To identify whether the addition of the peptide vaccine to high dose interleukin (IL)-2 (aldesleukin) can result in a clinical response rate which may be superior to that found in similar patients treated with high dose IL-2 alone.

SECONDARY OBJECTIVES:

I. To evaluate the toxicity profile of patients treated on this trial, according to the regimen received.

II. To compare the disease free/progression free survival of patients treated on both arms of the study.

III. To determine the immunologic response experienced by patients who have received the peptide vaccination, as measured by changes in T-cell precursors from before to after treatment.

IV. To evaluate the quality of life of patients before and after high-dose IL-2.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive aldesleukin intravenously (IV) over 15 minutes every 8 hours for 12 doses.

ARM II: Patients receive gp100 antigen emulsified in Montanide ISA-51 subcutaneously (SC) on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2.

In both arms, treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.

After completion of treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Melanoma
  • Stage IIIA Skin Melanoma
  • Stage IIIB Skin Melanoma
  • Stage IIIC Skin Melanoma
  • Stage IV Skin Melanoma
Intervention  ICMJE
  • Biological: Aldesleukin
    Given IV
    Other Name: Ro-236019
  • Biological: gp100 Antigen
    Given SC
    Other Names:
    • gp 100
    • gp100
  • Drug: Montanide ISA 51 VG
    Given SC
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
  • Other: Laboratory Biomarker Analysis
    Correlative studies
Study Arms  ICMJE
  • Experimental: Arm I (aldesleukin)
    Patients receive aldesleukin IV over 15 minutes every 8 hours for 12 doses. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
    Interventions:
    • Biological: Aldesleukin
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Other: Laboratory Biomarker Analysis
  • Experimental: Arm II (gp100 antigen in Montanide IDA-51 and aldesleukin)
    Patients receive gp100 antigen emulsified in Montanide ISA-51 SC on day 1. Patients also receive aldesleukin as in Arm I beginning on day 2. Treatment repeats every 3 weeks for 2 courses in the absence of disease progression or unacceptable toxicity. Patients with stable or responding disease 3 weeks after completing 2 courses may receive a maximum of 12 additional courses. Patients with complete response may receive a maximum of 2 additional courses.
    Interventions:
    • Biological: Aldesleukin
    • Biological: gp100 Antigen
    • Drug: Montanide ISA 51 VG
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Other: Laboratory Biomarker Analysis
Publications * Schwartzentruber DJ, Lawson DH, Richards JM, Conry RM, Miller DM, Treisman J, Gailani F, Riley L, Conlon K, Pockaj B, Kendra KL, White RL, Gonzalez R, Kuzel TM, Curti B, Leming PD, Whitman ED, Balkissoon J, Reintgen DS, Kaufman H, Marincola FM, Merino MJ, Rosenberg SA, Choyke P, Vena D, Hwu P. gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011 Jun 2;364(22):2119-27. doi: 10.1056/NEJMoa1012863.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 8, 2006)
185
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE May 2011
Actual Primary Completion Date May 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Any patient with measurable metastatic (stage IV or locally advanced stage III) cutaneous melanoma and an expected survival of greater than three months will be considered
  • Serum creatinine of 1.6 mg/dl or less
  • Total bilirubin 1.6 mg/dl or less
  • White blood cell (WBC) 3000/mm^3 or greater
  • Platelet count 90,000 mm^3 or greater
  • Serum aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less then three times normal
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Patients of both genders must be willing to practice effective birth control during this trial
  • Pathologic confirmation of cutaneous melanoma; patients may enter the study with a pathologic diagnosis of cutaneous melanoma from any institution; all slides will be reviewed at National Institutes of Health (NIH) (department of Anatomic Pathology) and if the diagnosis is not confirmed, the patient will be excluded from the study
  • Tissue type human leukocyte antigen (HLA) A0201

Exclusion Criteria:

  • Patients who have types of melanoma other than cutaneous, i.e. ocular or mucosal
  • Patients who are undergoing or have undergone in the past 4 weeks any other form of therapy except surgery for their cancer, including radiation therapy to any site
  • Patients who have active systemic infections, coagulation disorders, autoimmune disease or history of other major medical illnesses such as insulin dependent diabetes mellitus, cardiac ischemia, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary diseases and inflammatory bowel disorders
  • Patients who have significant psychiatric disease which in the opinion of the principal investigator would prevent adequate informed consent or render immunotherapy unsafe or contraindicated
  • Patients who require steroid therapy or steroid-containing compounds, or have used systemic steroids in the past 4 weeks, or have used topical or inhalational steroids in the past 2 weeks
  • Patients who are pregnant
  • Patients who are known to be positive for viral hepatitis B or C (hepatitis B surface antigen [HBsAg] or anti hepatitis C virus [HCV]) or human immunodeficiency virus (HIV) (HIV antibody)
  • Patients who have any form of primary or secondary immunodeficiency
  • Patients who have received previous high dose IL-2 (> 600,000 IU/kg)
  • Patients who have received previous gp100 vaccines
  • Patients who have an abnormal stress cardiac test (stress thallium, stress multi gated acquisition scan [MUGA], dobutamine echocardiogram or other stress test that will rule out cardiac ischemia)
  • Patients who have abnormal pulmonary function tests (forced expiratory volume in one second [FEV1] < 65% or forced vital capacity [FVC] < 65% of predicted)
  • Patients who have brain metastasis or history of brain metastasis
  • No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease free for 5 years
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00019682
Other Study ID Numbers  ICMJE NCI-2012-02897
NCI-2012-02897 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000066963
99-C-0051 ( Other Identifier: IU Health Goshen Center for Cancer Care )
T98-0085 ( Other Identifier: CTEP )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Cancer Institute (NCI)
Study Sponsor  ICMJE National Cancer Institute (NCI)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Douglas Schwartzentruber IU Health Goshen Center for Cancer Care
PRS Account National Cancer Institute (NCI)
Verification Date November 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP