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Dendritic Cells Plus Autologous Tumor RNA in Uveal Melanoma

Primary Purpose

Uveal Melanoma

Status
Active
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Autologous Dendritic Cells loaded with autologous Tumor RNA
Sponsored by
University Hospital Erlangen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Uveal Melanoma focused on measuring Uveal Melanoma, Monosomy 3

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must suffer from melanoma of the uvea (stage T2, T3 and T4 [AJCC TNM grading 2009]).
  • Uveal melanoma must be resected and display a monosomy for chromosome 3 (will be determined by a validated qualitative analysis of loss of heterozygosity). Tumor material has to be stored appropriately in RNAlater solution for RNA preparation.
  • The patient has to be free of detectable tumor at the time point of study enrollment (adjuvant setting), as assessed by clinical inspection, abdominal sonography, chest X-ray and evaluation of the tumor-marker S-100..
  • Patients must have a WHO performance status of 0, 1 or 2 and must be in stable medical condition.
  • Patients must be between 18 and 75 years old and must be able and willing to give informed consent.
  • Women of child-bearing age must have a negative pregnancy test, and must oblige to use effective contraception until at least 4 weeks after the last vaccination.
  • Patients must be willing to get hospitalized for at least 4 hours following vaccination(s), and to cooperate for the whole period of the trial.
  • Patients must have fully recovered from surgery.
  • Signed informed consent

Exclusion Criteria:

  • Any other major serious illness [e.g. active systemic infections, immunodeficiency disease, clinically significant heart disease, respiratory disease, bleeding disorders, cancer etc.] or a contraindication to leukapheresis.
  • Evidence for HIV-1, HIV -2, HTLV-1, HBV, or HCV infection.
  • Active autoimmune disease (such as but not limited to Lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis, inflammatory bowel disease). Vitiligo and pathological laboratory results (autoantibodies) without clinical symptoms are, however, not an exclusion criterion.
  • Previous splenectomy or radiation therapy to the spleen.
  • Patients with organ allografts.
  • Concomitant treatment with chemotherapy, immunotherapy, any investigational drug and paramedical substances. Patients may receive concomitant medications to control symptoms such as analgetics, antihypertensive medication, etc.
  • History of other active malignant neoplasm within the preceding 5 years (excluding non-melanoma skin cancer or carcinoma in situ of the cervix).
  • Organic brain syndrome or significant psychiatric abnormality which would impede informed consent and / or AND preclude participation in the full protocol and follow up.
  • Positive pregnancy test / Pregnancy or lactation. If pregnancy occurs during the course of the trial to female patients in arm A or B, the patient has to be excluded.
  • Detection of metastases. If uveal melanoma metastases appear during the course of the trial, the patient has to be excluded.
  • Lack of compliance of the patient.

Sites / Locations

  • Dept. of Dermatology, University Hospital
  • University Hospital Department of Ophtalmology
  • University Hospital Department of Ophtalmology
  • Städtisches Klinikum
  • University Hospital Department of Ophtalmology
  • University Hospital Department of Ophtalmology
  • University Hospital Department of Ophtalmology
  • University Hospital Department of Ophtalmology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

A

B

Arm Description

Biological/Vaccine; Autologous Dendritic Cells loaded with autologous Tumor RNA

Control, Standard of care, which is clinical control every 3 months

Outcomes

Primary Outcome Measures

Prolongation of Overall survival
Clinical staging every 3 months from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months, followed by telephone interviews.

Secondary Outcome Measures

Prolongation of disease free survival
Skin, lymph node and ophtalmological inspection , medical history, laboratory, and abdominal sonography will be performed every 3 months, chest x ray will be performed every 6 months

Full Information

First Posted
September 17, 2013
Last Updated
November 29, 2022
Sponsor
University Hospital Erlangen
Collaborators
University Hospital Lübeck, University Hospital Munich, Universitätsklinikum Hamburg-Eppendorf, University Hospital Homburg/Saar, Universitätsklinikum Köln, University Hospital Tuebingen, University Hospital, Essen, Wuerzburg University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01983748
Brief Title
Dendritic Cells Plus Autologous Tumor RNA in Uveal Melanoma
Official Title
A NON-COMMERCIAL, MULTICENTER, RANDOMIZED, TWO-ARMED, OPEN-LABEL PHASE III STUDY TO EVALUATE THE ADJUVANT VACCINATION WITH TUMOR RNA-LOADED AUTOLOGOUS DENDRITIC CELLS VERSUS OBSERVATION OF PATIENTS WITH RESECTED MONOSOMY 3 UVEAL MELANOMA
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 2014 (undefined)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Erlangen
Collaborators
University Hospital Lübeck, University Hospital Munich, Universitätsklinikum Hamburg-Eppendorf, University Hospital Homburg/Saar, Universitätsklinikum Köln, University Hospital Tuebingen, University Hospital, Essen, Wuerzburg University Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Patients suffering from uveal melanoma (typed positive for monosomy 3 and without evidence for metastases) will be vaccinated over a period of 2 years with Dendritic Cell loaded with autologous Tumor RNA. 200 patients will be included. The Trial is an open multicenter Phase III Trial.
Detailed Description
Trial arm A (DCaT-RNA) = Experimental intervention: Patients in arm A receive 8 vaccinations over a period of 2 years consisting of autologous, mature, monocyte-derived Dendritic Cells loaded with autologous tumor RNA (20 mio DC per vaccination); cells are given via intravenous infusions; vaccinations are followed by a 1 year observation (staging every 3 months) Trial arm B (Observation) = Control: Patients in arm B receive standard care (observation only with staging every 3 months)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Uveal Melanoma
Keywords
Uveal Melanoma, Monosomy 3

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
A
Arm Type
Experimental
Arm Description
Biological/Vaccine; Autologous Dendritic Cells loaded with autologous Tumor RNA
Arm Title
B
Arm Type
No Intervention
Arm Description
Control, Standard of care, which is clinical control every 3 months
Intervention Type
Biological
Intervention Name(s)
Autologous Dendritic Cells loaded with autologous Tumor RNA
Primary Outcome Measure Information:
Title
Prolongation of Overall survival
Description
Clinical staging every 3 months from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months, followed by telephone interviews.
Time Frame
Assessment every 3 months
Secondary Outcome Measure Information:
Title
Prolongation of disease free survival
Description
Skin, lymph node and ophtalmological inspection , medical history, laboratory, and abdominal sonography will be performed every 3 months, chest x ray will be performed every 6 months
Time Frame
Assessment every 3 months
Other Pre-specified Outcome Measures:
Title
Assessment for induction of immune responses
Time Frame
The induction of immune responses will be researched in selected patients (in a minimum of 15 survivors per trial arm) 2 years after randomization.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must suffer from melanoma of the uvea (stage T2, T3 and T4 [AJCC TNM grading 2009]). Uveal melanoma must be resected and display a monosomy for chromosome 3 (will be determined by a validated qualitative analysis of loss of heterozygosity). Tumor material has to be stored appropriately in RNAlater solution for RNA preparation. The patient has to be free of detectable tumor at the time point of study enrollment (adjuvant setting), as assessed by clinical inspection, abdominal sonography, chest X-ray and evaluation of the tumor-marker S-100.. Patients must have a WHO performance status of 0, 1 or 2 and must be in stable medical condition. Patients must be between 18 and 75 years old and must be able and willing to give informed consent. Women of child-bearing age must have a negative pregnancy test, and must oblige to use effective contraception until at least 4 weeks after the last vaccination. Patients must be willing to get hospitalized for at least 4 hours following vaccination(s), and to cooperate for the whole period of the trial. Patients must have fully recovered from surgery. Signed informed consent Exclusion Criteria: Any other major serious illness [e.g. active systemic infections, immunodeficiency disease, clinically significant heart disease, respiratory disease, bleeding disorders, cancer etc.] or a contraindication to leukapheresis. Evidence for HIV-1, HIV -2, HTLV-1, HBV, or HCV infection. Active autoimmune disease (such as but not limited to Lupus erythematosus, autoimmune thyroiditis or uveitis, multiple sclerosis, inflammatory bowel disease). Vitiligo and pathological laboratory results (autoantibodies) without clinical symptoms are, however, not an exclusion criterion. Previous splenectomy or radiation therapy to the spleen. Patients with organ allografts. Concomitant treatment with chemotherapy, immunotherapy, any investigational drug and paramedical substances. Patients may receive concomitant medications to control symptoms such as analgetics, antihypertensive medication, etc. History of other active malignant neoplasm within the preceding 5 years (excluding non-melanoma skin cancer or carcinoma in situ of the cervix). Organic brain syndrome or significant psychiatric abnormality which would impede informed consent and / or AND preclude participation in the full protocol and follow up. Positive pregnancy test / Pregnancy or lactation. If pregnancy occurs during the course of the trial to female patients in arm A or B, the patient has to be excluded. Detection of metastases. If uveal melanoma metastases appear during the course of the trial, the patient has to be excluded. Lack of compliance of the patient.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Beatrice Schuler-Thurner, MD
Organizational Affiliation
University Hospital Erlangen
Official's Role
Principal Investigator
Facility Information:
Facility Name
Dept. of Dermatology, University Hospital
City
Erlangen
State/Province
Bayern
ZIP/Postal Code
90154
Country
Germany
Facility Name
University Hospital Department of Ophtalmology
City
Erlangen
State/Province
Bayern
ZIP/Postal Code
91054
Country
Germany
Facility Name
University Hospital Department of Ophtalmology
City
Würzburg
State/Province
Bayern
ZIP/Postal Code
97080
Country
Germany
Facility Name
Städtisches Klinikum
City
Dessau
ZIP/Postal Code
06847
Country
Germany
Facility Name
University Hospital Department of Ophtalmology
City
Essen
ZIP/Postal Code
45122
Country
Germany
Facility Name
University Hospital Department of Ophtalmology
City
Homburg/Saar
ZIP/Postal Code
66421
Country
Germany
Facility Name
University Hospital Department of Ophtalmology
City
Lübeck
ZIP/Postal Code
23538
Country
Germany
Facility Name
University Hospital Department of Ophtalmology
City
Tübingen
ZIP/Postal Code
72076
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
26602097
Citation
Schuler-Thurner B, Bartz-Schmidt KU, Bornfeld N, Cursiefen C, Fuisting B, Grisanti S, Heindl LM, Holbach L, Keseru M, Knorr H, Koch K, Kruse F, Meiller R, Metz C, Meyer-ter-Vehn T, Much M, Reinsberg M, Schliep S, Seitz B, Schuler G, Susskind D, Viestenz A, Wagenfeld L, Zeschnigk M. [Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma]. Ophthalmologe. 2015 Dec;112(12):1017-21. doi: 10.1007/s00347-015-0162-z. German.
Results Reference
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Dendritic Cells Plus Autologous Tumor RNA in Uveal Melanoma

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