Melanoma (Skin)Phase 1NCT00390338
Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma
A Phase 1 study testing polarized dendritic cells and non-polarized dendritic cells in people with Melanoma (Skin), run by Pawel Kalinski at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma (Skin)
- What is being tested?
- polarized dendritic cells and non-polarized dendritic cells
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 2 sitesUnited States
- Study dates
- Oct 2006to Jan 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
UPMC Cancer Center at Magee-Womens Hospital
Pittsburgh, Pennsylvania, 15213
UPMC Cancer Centers
Pittsburgh, Pennsylvania, 15232
About this study
Official title: Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients With Metastatic Melanoma
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.
Read the 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.
- Conditions
- Melanoma (Skin)
- Being tested
- polarized dendritic cells, non-polarized dendritic cells
- Keywords
- recurrent melanoma, stage IV melanoma, stage IIIA melanoma, stage IIIB melanoma, stage IIIC melanoma
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
polarized dendritic cellsBiological
non-polarized dendritic cellsBiological
| Study group | Role | What they receive |
|---|---|---|
| peptide-pulsed type-1-polarized dendritic cells | Experimental | intralymphatic vaccination with peptide-pulsed type-1-polarized dendritic cells (aDC1) Receives: Biological: polarized dendritic cells |
| peptide-pulsed mature non-polarized dendritic cells (cDCs) | Experimental | intralymphatic vaccination with peptide-pulsed mature non-polarized dendritic cells (cDCs) Receives: Biological: non-polarized dendritic cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine
Measured: 7 years
Secondary outcomes (1)
Assess immune responses to each dendritic cell vaccine outcome
- 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.
Measured: 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2006 (estimated)
- Study startOct 2006
- Primary completionMay 2012
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Melanoma (Skin)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pawel Kalinski
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Pawel Kalinski, University of Pittsburgh
- Investigators
- Ahmad A. Tarhini, MD, MS, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00390338
- Sponsor's protocol ID
- 03-118
- Other IDs
- PCI-UPCI-03-118, NCI-7089, PCI-IRB-0409071, CDR0000504518, NCI-2009-00125
- Status last verified
- Sep 2017
- First submitted
- 18 Oct 2006
- Last updated
- 26 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT00390338
- Acronym / sponsor ID
- 03-118
- Conditions
- Melanoma (Skin)
- Keywords
- recurrent melanoma, stage IV melanoma, stage IIIA melanoma, stage IIIB melanoma, stage IIIC melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Pawel KalinskiUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Oct 2006
- Primary completion
- May 2012 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 19 Oct 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| peptide-pulsed type-1-polarized dendritic cells | Experimental | Biological: polarized dendritic cellsintralymphatic vaccination with peptide-pulsed type-1-polarized dendritic cells (aDC1) |
| peptide-pulsed mature non-polarized dendritic cells (cDCs) | Experimental | Biological: non-polarized dendritic cellsintralymphatic vaccination with peptide-pulsed mature non-polarized dendritic cells (cDCs) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| polarized dendritic cells | Biological | peptide-pulsed type-1-polarized dendritic cells |
| non-polarized dendritic cells | Biological | peptide-pulsed mature non-polarized dendritic cells (cDCs) |
Primary outcome
Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine
Time frame: 7 years
1 secondary outcome
Assess immune responses to each dendritic cell vaccine outcome
Time frame: 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ahmad A. Tarhini, MD, MS principal investigator
University of Pittsburgh
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing polarized dendritic cells and non-polarized dendritic cells in people with Melanoma (Skin), run by Pawel Kalinski at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine (time frame: 7 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2017.