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

This study has been completed.
Sponsor:
Information provided by:
José Mordoh, M.D., Ph.D.
ClinicalTrials.gov Identifier:
NCT00515983
First received: August 10, 2007
Last updated: NA
Last verified: August 2007
History: No changes posted
  Purpose

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 Intervention Phase
Melanoma
Biological: DC/Apo-Nec
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Subject)
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

Resource links provided by NLM:


Further study details as provided by José Mordoh, M.D., Ph.D.:

Primary Outcome Measures:
  • 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) ]

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

Enrollment: 16
Study Start Date: October 2004
Study Completion Date: December 2005
  Eligibility

Ages Eligible for Study:   17 Years to 60 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00515983

Locations
Argentina
Instituto Médico Alexander Fleming
Buenos Aires, Capital Federal, Argentina, 1426
Sponsors and Collaborators
José Mordoh, M.D., Ph.D.
Investigators
Study Director: José Mordoh, MD,PhD
  More Information

No publications provided by José Mordoh, M.D., Ph.D.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00515983     History of Changes
Other Study ID Numbers: 4484/04
Study First Received: August 10, 2007
Last Updated: August 10, 2007
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Keywords provided by José Mordoh, M.D., Ph.D.:
melanoma
dendritic cells
apoptotic/necrotic cells
therapeutic vaccine

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on April 15, 2014