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Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma

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ClinicalTrials.gov Identifier: NCT00390338
Recruitment Status : Completed
First Posted : October 19, 2006
Last Update Posted : September 26, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Pawel Kalinski, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE October 18, 2006
First Posted Date  ICMJE October 19, 2006
Last Update Posted Date September 26, 2017
Study Start Date  ICMJE October 2006
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2013)
Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine [ Time Frame: 7 years ]
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00390338 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2013)
Assess immune responses to each dendritic cell vaccine outcome [ Time Frame: 7 ]
i. Peripheral blood CD8+ and CD4+ T cell responses against HLA-presented melanoma epitopes, and (in patients with available tumor tissue) against autologous tumor cells, and using IFNγ-, and IL-5- ELISPOT assays. CD8+ T cell responses (IFNγ ELISPOT) will be used as a secondary readout: the sum of the specific ELISPOT counts obtained (at week 8) with each of the individual HLA-A2-restricted peptides (less the respective counts obtained before the treatment), will be considered as a primary indication of the vaccine effectiveness. ii. Delayed type hypersensitivity (DTH) response to the mix of the melanoma-related peptides, injected intradermally in vivo, and DTH to autologous tumor lysates, in all cases when autologous tumor tissue is available. iii. Delayed type hypersensitivity (DTH) responses to KLH and PADRE injected intradermally in vivo.
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 Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma
Official Title  ICMJE Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients With Metastatic Melanoma
Brief Summary

RATIONALE: Vaccines made from a person's dendritic cells mixed with tumor peptides and proteins may help the body build an effective immune response to kill tumor cells. Infusing the vaccine directly into the lymphatic system may cause a stronger immune response and kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects and best dose of two dendritic cell vaccines in treating patients with stage III or stage IV melanoma.

Detailed Description

OBJECTIVES:

Primary

  • Compare the safety of intralymphatic autologous type-1-polarized dendritic cell vaccine vs autologous mature dendritic cell vaccine loaded with antigenic peptides and proteins in patients with stage III or IV melanoma.

Secondary

  • Determine peripheral blood CD8+ and CD4+ T-cell responses to HLA-presented melanoma epitopes and autologous tumor cells using interferon gamma and interleukin-5 ELISPOT assay.
  • Compare the delayed-type hypersensitivity (DTH) responses to these regimens and DTH to autologous tumor lysates in these patients.
  • Compare the DTH response to keyhole limpet hemocyanin and pan-DR epitope (PADRE) in these patients.
  • Correlate treatment-associated changes in immune response with clinical outcome.

OUTLINE: This is a randomized, open-label, dose-escalation study. Patients are randomized to 1 of 2 formulations of dendritic cell (DC) vaccines.

  • Arm I: Patients receive intralymphatic autologous type-1-polarized (by interleukin-1-beta, tumor necrosis factor [TNF] alfa, interferon alfa, poly-I:C, and interferon gamma) DC vaccine that has been loaded with tumor-related peptide antigens (gp100:209-217[210M] peptide, tyrosinase peptide, MART-1:27-35 peptide, MAGE-3/6, and EphA2) and proteins (keyhole limpet hemocyanin [KLH; first course] or pan-DR epitope [PADRE] [second course]) every 6 hours on days 1-4 of weeks 1 and 6.
  • Arm II: Patients receive intralymphatic autologous mature (by interleukin-1-beta, TNF alfa, interleukin-6, and prostaglandin E_2) DC vaccine that has been loaded with tumor-related peptide antigens and proteins as in arm I every 6 hours on days 1-4 of weeks 1 and 6.

Patients achieving complete response receive 2 more courses of treatment (3 months apart). Patients achieving partial response receive up to 10 more courses of treatment (1 month apart) in the absence of disease progression or unacceptable toxicity.

In each arm, cohorts of 4-7 patients receive escalating doses of DC vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 7 patients experience dose-limiting toxicity.

Blood samples are obtained at baseline and periodically during and after treatment. Samples are examined by immunoenzyme techniques for immunologic measurements.

After completion of study therapy, patients are followed periodically for 10½ years and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma (Skin)
Intervention  ICMJE
  • Biological: polarized dendritic cells
  • Biological: non-polarized dendritic cells
Study Arms  ICMJE
  • Experimental: peptide-pulsed type-1-polarized dendritic cells
    intralymphatic vaccination with peptide-pulsed type-1-polarized dendritic cells (aDC1)
    Intervention: Biological: polarized dendritic cells
  • Experimental: peptide-pulsed mature non-polarized dendritic cells (cDCs)
    intralymphatic vaccination with peptide-pulsed mature non-polarized dendritic cells (cDCs)
    Intervention: Biological: non-polarized dendritic cells
Publications * Not Provided

*   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: October 14, 2013)
22
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE January 2015
Actual Primary Completion Date May 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Pathologically confirmed stage III or IVA (M1a) melanoma

    • Recurrent and inoperable disease
    • Any tumor thickness and any number of lymph nodes involved
    • Asymptomatic cutaneous and nodal disease allowed
    • Asymptomatic pulmonary metastatic disease (stage IVB, M1b) allowed
  • No advanced symptomatic visceral disease, including any symptomatic visceral organ involvement, or disease associated with increased serum lactic dehydrogenase > 2.5 times upper limit of normal (stage IVC, M1c)
  • Standard curative or palliative measures do not exist or are no longer effective
  • Sufficient numbers of monocytes (≥ 20 x 10^6) must be obtained for the preparation of the vaccine

    • If an insufficient number of cells is obtained on first venipuncture, a second venipuncture may be performed (not exceeding 550 mL of blood within 8 weeks)
  • No brain metastases by contrast-enhanced CT scan or MRI

    • Prior brain metastases allowed provided they were successfully treated and patient has been asymptomatic for ≥ 3 months
  • HLA-A2 positive

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy ≥ 6 months
  • Granulocyte count ≥ 1,500/mm³
  • Lymphocyte count ≥ 500/mm³
  • Platelet count > 70,000/mm³ (for venipuncture/pheresis procedure)
  • Creatinine ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Gamma-glutamyl transferase ≤ 2.5 times ULN
  • Lactic dehydrogenase ≤ 2.5 times ULN
  • Alkaline phosphatase ≤ 2.5 times ULN
  • Bilirubin ≤ 1.5 times ULN
  • No active infection
  • No sensitivity to drugs that provide local anesthesia
  • No pain uncontrolled by oral analgesics, including opiates and opiate analogs
  • No active autoimmune disease
  • No HIV, hepatitis B, or hepatitis C positivity
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • Negative pregnancy test
  • No other malignancy except for nonmelanoma skin cancers or carcinoma in situ of the cervix, or other malignancy for which the patient has been continuously disease-free for ≥ 2 years

PRIOR CONCURRENT THERAPY:

  • Recovered from prior surgery
  • No radiotherapy, chemotherapy, or immunotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
  • No antibiotics within the past 7 days
  • No systemic immunosuppressive agents, including steroids, within the past 4 weeks

    • Concurrent maintenance steroids for adrenal insufficiency allowed
  • No other concurrent anticancer investigational or commercial agents or therapies
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 NCT00390338
Other Study ID Numbers  ICMJE 03-118
PCI-UPCI-03-118
NCI-7089
PCI-IRB-0409071
CDR0000504518 ( Registry Identifier: PDQ (Physician Data Query) )
NCI-2009-00125 ( Registry Identifier: CTRP (Clinical Trials Reporting System) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Pawel Kalinski, University of Pittsburgh
Study Sponsor  ICMJE Pawel Kalinski
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Ahmad A. Tarhini, MD, MS University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date September 2017

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