Trial of Vaccine Therapy With mRNA- Transfected Dendritic Cells in Patients With Advanced Malignant Melanoma

Phase I/II Trial of Vaccine Therapy With mRNA- Transfected Dendritic Cells in Patients With Advanced Malignant Melanoma

PRIMARY OBJECTIVES: Determination of safety and toxicity of vaccination with patients' tumour mRNA transfected DCs .

SECONDARY OBJECTIVES:Determine immunological response to the vaccine (induction of specific T-cell response) and assessment of tumour response

Study Overview

• Status: Completed
• Conditions: Malignant Melanoma
• Intervention / Treatment: Biological: Dendritic Cells (DC) malignant melanoma; Procedure: IL-2

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Accessible tumour tissue for vaccine production (extraction of tumour mRNA) i.e.subcutaneous or lymph node metastases.
• Must be at least 18 years of age.
• Must have histologically confirmed advanced, metastatic cutaneous melanoma no longer amenable for surgery.
• Must have evidence of disease progression and measurable or evaluable metastases
• Must be ambulatory with a ECOG performance score of <2
• Must have lab.values as following :

ANC > 1.5 x 109/L; platelets > 100 x 109/L, Hb > 9g/dL (> 5.6 mmol/L). Creatinine < 140 µmol/L (1.6 mg/dL); if borderline, the creatinine clearance > 40 mL/min, Bilirubin < 20% above the upper limit of normal, ASAT and ALAT < 2.5 the upper limit of normal. Albumin > 2.5 g/L.

• Prior radiotherapy: A minimum of 4 weeks (8 weeks in case of extensive radiotherapy) must have elapsed between the end of the prior radiotherapy and entry into the protocol.
• Prior chemotherapy: A minimum 4 weeks must have elapsed between the end of the prior chemotherapy and entry into the protocol.
• Signed informed consent of the patients for the treatment and follow up must be obtained and documented according to the ICH-GCP Guidelines.

Exclusion Criteria:

• History of prior malignancy other than melanoma, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin and ca. cervix stage 1B.
• Active infection requiring antibiotic therapy.
• Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia.
• Autoimmune disease currently treated with steroids.
• Adverse reactions to vaccines such as anaphylaxis or other serious reactions.
• History of immunodeficiency or autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, polymyositis-dermatomyositis, juvenile onset insulin dependent diabetes, or a vasculitic syndrome.
• Chemotherapy or other potentially immune-suppressive therapy that has been administered within 4 weeks prior to vaccination.
• Pregnancy or lactation.
• Any reason why, in the opinion of the investigator, the patient should not participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dendritic Cells (DC) malignant melanoma; 22 patients were included in this arm.	Biological: Dendritic Cells (DC) malignant melanoma; The patients were assigned to intradermal or intranodal DC vaccination
EXPERIMENTAL: DC vaccine plus IL-2; To improve the efficacy of the DC vaccine, IL-2 was administrated at the vaccination site through direct lymph node injection. 9 patients were included in this arm.	Biological: Dendritic Cells (DC) malignant melanoma; The patients were assigned to intradermal or intranodal DC vaccination; Procedure: IL-2; IL-2 were administrated by intranodal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of safety and toxicity of vaccination with patients' tumour mRNA transfected DCs	Biochemistry and hematology results, vital signs and ECOG performance status are measured at those timepoints.	Patients are coming every week during 6 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine immunological response to the vaccine (induction of specific T-cell response)		6 weeks and 3 months after study start
Assessment of tumour response.	CT-scan	3 months after study start

Collaborators and Investigators

• Sponsor: Oslo University Hospital

Publications and helpful links

General Publications

• Kyte JA, Mu L, Aamdal S, Kvalheim G, Dueland S, Hauser M, Gullestad HP, Ryder T, Lislerud K, Hammerstad H, Gaudernack G. Phase I/II trial of melanoma therapy with dendritic cells transfected with autologous tumor-mRNA. Cancer Gene Ther. 2006 Oct;13(10):905-18. doi: 10.1038/sj.cgt.7700961. Epub 2006 May 5.
• Kyte JA, Kvalheim G, Lislerud K, thor Straten P, Dueland S, Aamdal S, Gaudernack G. T cell responses in melanoma patients after vaccination with tumor-mRNA transfected dendritic cells. Cancer Immunol Immunother. 2007 May;56(5):659-75. doi: 10.1007/s00262-006-0222-y. Epub 2006 Sep 1.

Study record dates

Study Major Dates

• Study Start: March 1, 2002
• Primary Completion (ACTUAL): February 1, 2006
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: January 17, 2011
• First Submitted That Met QC Criteria: January 18, 2011
• First Posted (ESTIMATE): January 19, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): August 15, 2016
• Last Update Submitted That Met QC Criteria: August 12, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma
• Other Study ID Numbers: DC malignant melanoma