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Vaccination of Melanoma Patients With Dendritic Cells Loaded With Allogeneic Apoptotic-Necrotic Melanoma Cells

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00515983
Recruitment Status : Completed
First Posted : August 14, 2007
Last Update Posted : August 14, 2007
Sponsor:
Information provided by:
José Mordoh, M.D., Ph.D.

Study Description
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Brief 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).

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.


Condition or disease Intervention/treatment Phase
Melanoma Biological: DC/Apo-Nec Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
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
Study Start Date : October 2004
Actual Study Completion Date : December 2005

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma Vaccines

Arms and Interventions
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Outcome Measures
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Primary Outcome Measures :
  1. Toxicity measured according to the NCI-Common Toxicity Criteria. [ Time Frame: 115 days follow up per Subject (Trial duration) ]
  2. Induction of immune responses associated to different vaccine doses [ Time Frame: 115 days follow up per subject (Trial duration) ]

Secondary Outcome Measures :
  1. Feasibility [ Time Frame: 115 days follow up per subject (Trial duration) ]

Eligibility Criteria
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Ages Eligible for Study:   17 Years to 60 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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)
  • 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00515983


Locations
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Argentina
Instituto Médico Alexander Fleming
Buenos Aires, Capital Federal, Argentina, 1426
Sponsors and Collaborators
José Mordoh, M.D., Ph.D.
Investigators
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Study Director: José Mordoh, MD,PhD
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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ClinicalTrials.gov Identifier: NCT00515983    
Other Study ID Numbers: 4484/04
First Posted: August 14, 2007    Key Record Dates
Last Update Posted: August 14, 2007
Last Verified: August 2007
Keywords provided by José Mordoh, M.D., Ph.D.:
melanoma
dendritic cells
apoptotic/necrotic cells
therapeutic vaccine
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas