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A Study on the Safety and Immunogenicity of Combined Intradermal and Intravenous Administration of an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Previously Treated Unresectable Stage III or IV Melanoma

Primary Purpose

Melanoma

Status

Completed

Phase

Phase 1

Locations

Belgium

Study Type

Interventional

Intervention

TriMix-DC

About this trial

This is an interventional treatment trial for Melanoma focused on measuring stage IIIC/IV melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Able and willing to give valid written informed consent before undergoing any study-related activities.
Patients with histological documentation of AJCC stage III or IV melanoma of the skin, mucosa, eye or unknown primary.
Unable to undergo resection of all metastatic disease.
Negative serology for HBV, HCV, HIV and Syphilis. If positive results for HepB or Syphilis indicate immunity and are not indicative of active infection, the patient can enter the study.
Adequate venous access that allows to undergo leucapheresis.
Having failed first line treatment with DTIC based chemotherapy
Full recovery from all prior therapies. A minimum of 4 weeks (6 weeks in case of prior treatment with nitrosurea or Mitomycin C) should separate the last day of prior treatment administration and the date of informed consent.
WHO performance status of 0, 1 or 2 (see Appendix D).
Male and female patients ≥ 18 years of age.
Laboratory parameters should be within normal range, except for the following laboratory parameters, which must be within the ranges specified:see protocol.
Viral tests:HIV,HBV and HCV
Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study.
Patients must be willing to cooperate for the whole period of the study.

Exclusion Criteria:

Evidence of immunodeficiency. Autoimmune disease requiring medical treatment
Any serious acute or chronic illnesses or other conditions requiring concurrent medications not allowed during this study.
History of malignancy.
Inability to undergo PET/CT or MRI examination.
Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study.
Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment.
Subject is pregnant or is currently breast-feeding, anticipates becoming pregnant/ impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessary, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment.
Current alcohol dependence or drug abuse.
Known hypersensitivity to the study treatment.
Legal incapacity or limited legal capacity.
Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.

Sites / Locations

UZ Brussel

Outcomes

Primary Outcome Measures

a new tumor evaluation (PET/CT)

Secondary Outcome Measures

Document the anti-melanoma activity

Full Information

NCT ID

NCT01066390

First Posted

January 8, 2010

Last Updated

May 5, 2014

Sponsor

Bart Neyns

1. Study Identification

Unique Protocol Identification Number

NCT01066390

Brief Title

A Study on the Safety and Immunogenicity of Combined Intradermal and Intravenous Administration of an Autologous mRNA Electroporated Dendritic Cell Vaccine in Patients With Previously Treated Unresectable Stage III or IV Melanoma

Study Type

Interventional

2. Study Status

Record Verification Date

August 2012

Overall Recruitment Status

Completed

Study Start Date

December 2009 (undefined)

Primary Completion Date

November 2013 (Actual)

Study Completion Date

May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Bart Neyns

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This phase I study plan is divided in the following four phases: Eligibility Screen Phase (week -4 to -1): Following written informed consent patients with metastatic melanoma (AJCC stage III/IV with unresectable disease) will undergo an eligibility screen (incl. blood analysis and PET/CT-scan). TriMix-DC Vaccine Manufacturing Phase (week I to IV): eligible patients will undergo a leucapheresis (15 liter of venous blood) for the preparation of autologous TriMix-DC vaccine. Vaccine preparations will be manufactured and quality-controlled (during an interval of 4 weeks following the leucapheresis) and released for patient administration if the TriMix-DC preparation fulfills the predefined quality requirements. TriMix-DC Vaccine Administration Phase (Week 1 to 24): 4 weeks after the leucapheresis patients will initiate therapeutic vaccination with the TriMix-DC vaccine by IV and ID administration. The vaccines will be administered at 4 different visits that will be separated with an interval of 2 weeks. At each vaccination a total of 12.106 DC per antigen will be administered. Patients will be allocated to three different cohorts: The first cohort will receive 10% of TriMix-DC by iv and 90% by id injection. The second cohort 25% by iv and 75% by id injection. The third cohort 50% by iv and 50% by id injection. During the week following the administration of the fourth vaccine (= week 8), a DTH-test and punch biopsy of the injection site will be performed as well as a second leucapheresis (for the purpose of immuno-monitoring) and tumor evaluation (by PET-CT). A fifth vaccine will be administered and a repeat tumor staging performed in week 16 (= 8w after the fourth vaccine). End of study visit: Patients will perform an "end of study visit" 8 weeks after the fifth vaccine (= week 24) as well as a new tumor evaluation (PET/CT). Follow-up Phase: survival data will be obtained until 3 years after the initiation of vaccine therapy or the time of death.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

stage IIIC/IV melanoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

TriMix-DC

Intervention Description

eligible patients will undergo a leucapheresis for the preparation of autologous TriMix-DC vaccine.4 weeks after the leucapheresis patients will initiate therapeutic vaccination with the TriMix-DC vaccine by IV and ID administration. The vaccines will be administered at 4 different visits that will be separated with an interval of 2 weeks.

Primary Outcome Measure Information:

Title

a new tumor evaluation (PET/CT)

Time Frame

24 weeks

Secondary Outcome Measure Information:

Title

Document the anti-melanoma activity

Time Frame

week 8, 16 and 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Able and willing to give valid written informed consent before undergoing any study-related activities. Patients with histological documentation of AJCC stage III or IV melanoma of the skin, mucosa, eye or unknown primary. Unable to undergo resection of all metastatic disease. Negative serology for HBV, HCV, HIV and Syphilis. If positive results for HepB or Syphilis indicate immunity and are not indicative of active infection, the patient can enter the study. Adequate venous access that allows to undergo leucapheresis. Having failed first line treatment with DTIC based chemotherapy Full recovery from all prior therapies. A minimum of 4 weeks (6 weeks in case of prior treatment with nitrosurea or Mitomycin C) should separate the last day of prior treatment administration and the date of informed consent. WHO performance status of 0, 1 or 2 (see Appendix D). Male and female patients ≥ 18 years of age. Laboratory parameters should be within normal range, except for the following laboratory parameters, which must be within the ranges specified:see protocol. Viral tests:HIV,HBV and HCV Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the study. Patients must be willing to cooperate for the whole period of the study. Exclusion Criteria: Evidence of immunodeficiency. Autoimmune disease requiring medical treatment Any serious acute or chronic illnesses or other conditions requiring concurrent medications not allowed during this study. History of malignancy. Inability to undergo PET/CT or MRI examination. Mental impairment that may compromise the ability to give informed consent and comply with the requirements of the study. Participation in any other clinical trial involving another investigational agent within 4 weeks prior to enrollment. Subject is pregnant or is currently breast-feeding, anticipates becoming pregnant/ impregnating their partner during the study or within 6 months after study participation, or subject does not agree to follow acceptable methods of birth control, such as hormonal contraception, intra-uterine pessary, condoms or sterilization, to avoid conception during the study and for at least 6 months after receiving the last dose of study treatment. Current alcohol dependence or drug abuse. Known hypersensitivity to the study treatment. Legal incapacity or limited legal capacity. Presence of any psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from such.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bart Neyns, Professor

Organizational Affiliation

Universitair Ziekenhuis Brussel

Official's Role

Principal Investigator

Facility Information:

Facility Name

UZ Brussel

City

Laken

State/Province

Brussels

ZIP/Postal Code

1090

Country

Belgium

12. IPD Sharing Statement

Citations:

PubMed Identifier

23904461

Citation

Wilgenhof S, Van Nuffel AMT, Benteyn D, Corthals J, Aerts C, Heirman C, Van Riet I, Bonehill A, Thielemans K, Neyns B. A phase IB study on intravenous synthetic mRNA electroporated dendritic cell immunotherapy in pretreated advanced melanoma patients. Ann Oncol. 2013 Oct;24(10):2686-2693. doi: 10.1093/annonc/mdt245. Epub 2013 Jul 31.

Results Reference

derived

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