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Completed

NCT Number: NCT00515983

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

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.

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Key information

Conditions

Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

17 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Instituto Médico Alexander Fleming

Buenos Aires, Buenos Aires F.D., 1426, Argentina

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

DC/Apo-Nec

Biological

Primary outcomes

  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 outcomes

  1. Feasibility

    Time frame: 115 days follow up per subject (Trial duration)

Sponsors and collaborators

Lead sponsor

José Mordoh, M.D., Ph.D.

Other

Registry information

Official study 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

Important dates

Study start
2004
Study completion
2005
First posted
Aug 14, 2007
Registry last updated
Aug 14, 2007

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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