MelanomaPhase 1NCT00515983
Vaccination of Melanoma Patients With Dendritic Cells Loaded With Allogeneic Apoptotic-Necrotic Melanoma Cells
A Phase 1 study testing DC/Apo-Nec in people with Melanoma, run by José Mordoh, M.D., Ph.D. at 1 site in Argentina.
Trial summary
Background: Sixteen melanoma patients (1 stage IIC, 8 stage III, and 7 stage IV) were treated in a Phase I study to evaluate safety and immune responses, with a vaccine (DC/Apo-Nec) composed of autologous dendritic cells (DCs) loaded with a mixture of apoptotic/necrotic melanoma cell lines (Apo-Nec). Read more about this study
- Who is it for?
- Ages 17 to 60 years
- Conditions the study is for
- Melanoma
- What is being tested?
- DC/Apo-Nec
- How many people
- 16 participants
- Where
- 1 siteArgentina
- Study dates
- Oct 2004to Dec 2005
- 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 17 to 60 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- histologically confirmed cutaneous melanoma stages IIB, IIC, III or IV (AJCC)
- pts with minimal or non-detectable disease (NED) after surgery as asserted by CAT scans. Melanoma pts with unknown primary tumor site could be included in the study
- life expectancy > 6 months
- ages:from 15 to 60 years
- performance status (ECOG) 0 or 1
- pts with stage III disease had to be previously treated with IFN-alpha, and either finished the treatment or suspended it due to disease progression, toxicity or other clinical reasons. Alternatively, those pts who had not started IFN-alpha within six months after surgery could be included in this study
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- a suitable venous access for the leukapheresis procedure
- laboratory eligibility criteria included: hemoglobin > 10 gr %; WBC count > 4800/mm3, platelets > 150.000/mm3, total and direct bilirubin, serum oxalacetic transaminase and glutamic pyruvic transaminase < 1.5 fold the upper normal value; LDH < 450 mU/ml
- absence of pregnancy, with serum βHCG determined one week before vaccination in premenopausal women
- serum creatinine < 1.4 mg %
- no chemotherapy, radiotherapy or any biological treatments during the previous month
- no concurrent medication with corticosteroids or NSAIDs
- l no active brain metastases m- normal ECG
- all pts gave written informed consent before inclusion in the Study.
Who cannot join
- Ocular melanoma or melanoma of mucosa
- Active brain metastases
- Other previous carcinoma (with the exeption of cervical or in situ basal cells carcinoma adequately treated)
- Pregnant or breast-feeding women
- Cardiac Arythmia, severe heart disease.
- Bacterial, mycotic or viral serious infections ( > grade 2 according to NCI common toxicity criteria)
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- HIV, B or C Hepatitis previous infection
- Primary or secondary immunodeficiencies
- Other diseases that require treatment with regular corticoids or non steroids anti-inflammatory drugs or COX-2 inhibitors
Trial locations and contacts
1 site in 1 country.
Argentina1 site
Instituto Médico Alexander Fleming
Buenos Aires, Buenos Aires F.D., 1426
About this study
Official title: Phase I Clinical Trial of a Therapeutic Vaccine Composed of Autologous Dendritic Cells Loaded With Allogeneic Apoptotic Tumor Cells in Patients With Melanoma Stages IIB, IIC, III and IV
Background: Sixteen melanoma patients (1 stage IIC, 8 stage III, and 7 stage IV) were treated in a Phase I study to evaluate safety and immune responses, with a vaccine (DC/Apo-Nec) composed of autologous dendritic cells (DCs) loaded with a mixture of apoptotic/necrotic melanoma cell lines (Apo-Nec).
Methods: PBMC were obtained from leukapheresis and DCs were generated from monocytes cultured in the presence of GM-CSF and IL-4 in serum-free medium. Immature DCs (iDCs) were loaded with gamma-irradiated Apo-Nec cells and injected id without adjuvant. Cohorts of four patients were given four vaccines with 5, 10, 15, or 20 x106 DC/Apo-Nec per vaccine, two weeks apart.
Read more
Results: The vaccine was well tolerated in all patients. Toxicity to vaccine was mild, and the toxicity-limiting dose has not been reached. We found that 42.3 ±13.7 % melanoma patients´ iDCs were able to phagocyte Apo-Nec cells wich induced DCs maturation, as evidenced by increased expression of CD83, CD80, CD86, HLA class I and II compared to iDCs. Also, after phagocytosis, a 75.2 ±16 % reduction in Dextran-FITC endocytosis was observed compared to iDCs. CCR7 was upregulated upon Apo-Nec phagocytosis in DCs from all patients and accordingly in vitro DC/Apo-Nec cells were able to migrate towards MIP-3 beta. The DTH score increased significatively in the patients after the first vaccination and slightly decreased by the fourth vaccine (Mann-Whitney Test, p<0.05). For patient #1 a positive DTH reaction was detected to her own tumor irradiated cells. The presence of CD8+ T lymphocytes specific to gp100 and Melan A/MART-1 Ags were studied by tetramers binding in HLA-A*0201 patients (7 /15 patients) before and after vaccination. Two patients who remain NED increased Ags their specific T lymphocytes after vaccination. No humoral responses to Apo-Nec cells were detected. With a mean follow-up of 44.5 months post-surgery, the stage IIC pt is NED, 7/8 stage III pts are NED and 7/7 stage IV patients have progressed.
Conclussions: We conclude that DC/Apo-Nec vaccine is well tolerated, it induces specific immunity against melanoma Ags and in stage III patients it may prolong disease-free survival, affording protection from relapse in an adjuvant setting.
- Conditions
- Melanoma
- Being tested
- DC/Apo-Nec
- Keywords
- melanoma, dendritic cells, apoptotic/necrotic cells, therapeutic vaccine
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DC/Apo-NecBiological
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity measured according to the NCI-Common Toxicity Criteria.
Measured: 115 days follow up per Subject (Trial duration)
Induction of immune responses associated to different vaccine doses
Measured: 115 days follow up per subject (Trial duration)
Secondary outcomes (1)
Feasibility
Measured: 115 days follow up per subject (Trial duration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2007 (estimated)
- Study startOct 2004
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MelanomaStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- José Mordoh, M.D., Ph.D.
- Sponsor type
- University, hospital or other
- Investigators
- José Mordoh, MD,PhD, Study director
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00515983
- Sponsor's protocol ID
- 4484/04
- Status last verified
- Aug 2007
- First submitted
- 10 Aug 2007
- Last updated
- 14 Aug 2007
- Results posted
- No
Publications
von Euw EM, Barrio MM, Furman D, Levy EM, Bianchini M, Peguillet I, Lantz O, Vellice A, Kohan A, Chacon M, Yee C, Wainstok R, Mordoh J. A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10 -1082 promoter genotype as predictor of disease progression. J Transl Med. 2008 Jan 25;6:6. doi: 10.1186/1479-5876-6-6.
PubMed 18221542
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Trial of a Therapeutic Vaccine Composed of Autologous Dendritic Cells Loaded With Allogeneic Apoptotic Tumor Cells in Patients With Melanoma Stages IIB, IIC, III and IV
- ClinicalTrials.gov ID
- NCT00515983
- Acronym / sponsor ID
- 4484/04
- Conditions
- Melanoma
- Keywords
- melanoma, dendritic cells, apoptotic/necrotic cells, therapeutic vaccine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- José Mordoh, M.D., Ph.D.University, hospital or other
- Study start
- Oct 2004
- Study completion
- Dec 2005 (actual)
- First posted
- 14 Aug 2007 (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.
Background: Sixteen melanoma patients (1 stage IIC, 8 stage III, and 7 stage IV) were treated in a Phase I study to evaluate safety and immune responses, with a vaccine (DC/Apo-Nec) composed of autologous dendritic cells (DCs) loaded with a mixture of apoptotic/necrotic melanoma cell lines (Apo-Nec).
Methods: PBMC were obtained from leukapheresis and DCs were generated from monocytes cultured in the presence of GM-CSF and IL-4 in serum-free medium. Immature DCs (iDCs) were loaded with gamma-irradiated Apo-Nec cells and injected id without adjuvant. Cohorts of four patients were given four vaccines with 5, 10, 15, or 20 x106 DC/Apo-Nec per vaccine, two weeks apart.
Results: The vaccine was well tolerated in all patients. Toxicity to vaccine was mild, and the toxicity-limiting dose has not been reached. We found that 42.3 ±13.7 % melanoma patients´ iDCs were able to phagocyte Apo-Nec cells wich induced DCs maturation, as evidenced by increased expression of CD83, CD80, CD86, HLA class I and II compared to iDCs. Also, after phagocytosis, a 75.2 ±16 % reduction in Dextran-FITC endocytosis was observed compared to iDCs. CCR7 was upregulated upon Apo-Nec phagocytosis in DCs from all patients and accordingly in vitro DC/Apo-Nec cells were able to migrate towards MIP-3 beta. The DTH score increased significatively in the patients after the first vaccination and slightly decreased by the fourth vaccine (Mann-Whitney Test, p<0.05). For patient #1 a positive DTH reaction was detected to her own tumor irradiated cells. The presence of CD8+ T lymphocytes specific to gp100 and Melan A/MART-1 Ags were studied by tetramers binding in HLA-A*0201 patients (7 /15 patients) before and after vaccination. Two patients who remain NED increased Ags their specific T lymphocytes after vaccination. No humoral responses to Apo-Nec cells were detected. With a mean follow-up of 44.5 months post-surgery, the stage IIC pt is NED, 7/8 stage III pts are NED and 7/7 stage IV patients have progressed.
Conclussions: We conclude that DC/Apo-Nec vaccine is well tolerated, it induces specific immunity against melanoma Ags and in stage III patients it may prolong disease-free survival, affording protection from relapse in an adjuvant setting.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Single blind (participant)
Who may qualify
- Ages
- 17 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- histologically confirmed cutaneous melanoma stages IIB, IIC, III or IV (AJCC)
- pts with minimal or non-detectable disease (NED) after surgery as asserted by CAT scans. Melanoma pts with unknown primary tumor site could be included in the study
- life expectancy > 6 months
- ages:from 15 to 60 years
- performance status (ECOG) 0 or 1
Key exclusion criteria (9 listed)
- Ocular melanoma or melanoma of mucosa
- Active brain metastases
- Other previous carcinoma (with the exeption of cervical or in situ basal cells carcinoma adequately treated)
- Pregnant or breast-feeding women
- Cardiac Arythmia, severe heart disease.
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 |
|---|---|---|
| DC/Apo-Nec | Biological | – |
Primary outcome
Toxicity measured according to the NCI-Common Toxicity Criteria.
Time frame: 115 days follow up per Subject (Trial duration)
Induction of immune responses associated to different vaccine doses
Time frame: 115 days follow up per subject (Trial duration)
1 secondary outcome
Feasibility
Time frame: 115 days follow up per subject (Trial duration)
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 14 Aug 2007.
- Derived from this study: PubMed 18221542von Euw EM, Barrio MM, Furman D, Levy EM, Bianchini M, Peguillet I, Lantz O, Vellice A, Kohan A, Chacon M, Yee C, Wainstok R, Mordoh J. A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10 -1082 promoter genotype as predictor of disease progression. J Transl Med. 2008 Jan 25;6:6. doi: 10.1186/1479-5876-6-6.
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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.
José Mordoh, MD,PhD study director
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing DC/Apo-Nec in people with Melanoma, run by José Mordoh, M.D., Ph.D. at 1 site in Argentina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 9 exclusion criteria. 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 14 Aug 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Argentina. 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?
Toxicity measured according to the NCI-Common Toxicity Criteria. (time frame: 115 days follow up per Subject (Trial duration)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00515983, which also lists 1 linked publication.
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 14 Aug 2007.