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

Primary Purpose

Melanoma (Skin)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
polarized dendritic cells
non-polarized dendritic cells
Sponsored by
Pawel Kalinski
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Melanoma (Skin) focused on measuring recurrent melanoma, stage IV melanoma, stage IIIA melanoma, stage IIIB melanoma, stage IIIC melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UPMC Cancer Center at Magee-Womens Hospital
  • UPMC Cancer Centers

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

peptide-pulsed type-1-polarized dendritic cells

peptide-pulsed mature non-polarized dendritic cells (cDCs)

Arm Description

intralymphatic vaccination with peptide-pulsed type-1-polarized dendritic cells (aDC1)

intralymphatic vaccination with peptide-pulsed mature non-polarized dendritic cells (cDCs)

Outcomes

Primary Outcome Measures

Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine

Secondary Outcome Measures

Assess immune responses to each dendritic cell vaccine outcome
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.

Full Information

First Posted
October 18, 2006
Last Updated
September 25, 2017
Sponsor
Pawel Kalinski
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00390338
Brief Title
Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma
Official Title
Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients With Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
October 2006 (undefined)
Primary Completion Date
May 2012 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Pawel Kalinski
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Melanoma (Skin)
Keywords
recurrent melanoma, stage IV melanoma, stage IIIA melanoma, stage IIIB melanoma, stage IIIC melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
peptide-pulsed type-1-polarized dendritic cells
Arm Type
Experimental
Arm Description
intralymphatic vaccination with peptide-pulsed type-1-polarized dendritic cells (aDC1)
Arm Title
peptide-pulsed mature non-polarized dendritic cells (cDCs)
Arm Type
Experimental
Arm Description
intralymphatic vaccination with peptide-pulsed mature non-polarized dendritic cells (cDCs)
Intervention Type
Biological
Intervention Name(s)
polarized dendritic cells
Intervention Type
Biological
Intervention Name(s)
non-polarized dendritic cells
Primary Outcome Measure Information:
Title
Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine
Time Frame
7 years
Secondary Outcome Measure Information:
Title
Assess immune responses to each dendritic cell vaccine outcome
Description
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.
Time Frame
7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ahmad A. Tarhini, MD, MS
Organizational Affiliation
University of Pittsburgh
Official's Role
Principal Investigator
Facility Information:
Facility Name
UPMC Cancer Center at Magee-Womens Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
UPMC Cancer Centers
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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