We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
ClinicalTrials.gov Menu

Intratumoral Injection of Autologous CD1c (BDCA-1)+ Myeloid Dendritic Cells Plus Talimogene Laherparepvec (T-VEC) (myDCTV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03747744
Recruitment Status : Active, not recruiting
First Posted : November 20, 2018
Last Update Posted : December 29, 2020
Information provided by (Responsible Party):
Universitair Ziekenhuis Brussel

Brief Summary:
Over the past few years it has become evident that cancer cells can be recognized by the patient's own immune system. The immunological mechanisms at play are often referred to as the "cancer immune cycle" (Chen and Mellman 2013; Mellman 2013; Chen and Mellman 2017).In immune-evasive tumors a pivotal role has been attributed to myeloid dendritic cells (myDC) in regulating the activity of anti-tumor CTL activity within the TME (Broz, Binnewies et al. 2014). In animal models, myDC have been demonstrated to play an essential role in "licensing" anti-tumor CTLs to eradicate tumor cells. These myDC also migrate to tumor-draining lymph nodes and present tumor antigens to T-cells in these secondary lymphoid organs (Roberts, Broz et al. 2016). Human myDCs exist in two subsets that are differentiated by expression of either the BDCA-1 or BDCA-3 surface marker. The CD1c (BDCA-1)+ antigen is specifically expressed on human dendritic cells, which are CD11chighCD123low and represent the major subset of myDCs in human blood (about 0.6 % of all peripheral blood mononuclear cells (PBMCs)). CD1c (BDCA-1)+ myDC play an important role in the cross-presentation of tumor antigens following immunogenic cell death (Di Blasio, Wortel et al. 2016). Under conditions of tumor growth, myDC will be poorly recruited to the tumor microenvironment, do not get activated and thereby fail to efficiently coordinate anti-tumor immunity within the tumor micro-environment and present tumor associated antigens within tumor-draining lymph nodes. Talimogene laherparepvec (T-VEC) is a first-in-class oncolytic virus based on a modified herpes simplex virus (HSV) type 1 designed to selectively replicate in and lyse tumor cells while promoting regional and systemic antitumor immunity. In this phase I clinical trial we propose to investigate the safety of intratumoral injection of autologous CD1c (BDCA-1)+ myDC in non-visceral metastases of melanoma plus intratumoral injection of T-VEC (at its approved dose and regimen for the treatment of melanoma). We hypothesize that CD1c (BDCA-1)+ myDC in the T-VEC inflamed tumor microenvironment of the metastasis will capture tumor antigens in vivo and through cross-presentation of these antigens coordinate an effective anti-tumor T-cell response.

Condition or disease Intervention/treatment Phase
Melanoma Other: CD1c (BDCA-1)+ myDC Phase 1

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Intratumoral injection of T-VEC followed by intratumoral injection of CD1c (BDCA-1)+ myDC
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial on Intratumoral Injection of Autologous CD1c (BDCA-1)+ Myeloid Dendritic Cells Plus Talimogene Laherparepvec (T-VEC)
Actual Study Start Date : September 28, 2018
Estimated Primary Completion Date : October 1, 2023
Estimated Study Completion Date : October 1, 2023

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: CD1c (BDCA-1)+ myDC
CD1c (BDCA-1)+ myDC
Other: CD1c (BDCA-1)+ myDC
Intratumoral injection in subcutaneous, cutaneous, soft tissue metastases
Other Name: intratumoral injection of talimogene laherparepvec (T-VEC)

Primary Outcome Measures :
  1. Number of participants with treatment-related adverse events will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: through study completion, up to 1 year ]
    Safety of intratumoral injection with CD1c (BDCA-1)+ myDC and intratumoral injection of T-VEC

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subject has provided informed consent prior to initiation of any study-specific activities/procedures.
  • Male or female age ≥ 18 years at the time of informed consent
  • All subjects must have histologically confirmed advanced melanoma that cannot be completely surgically resected and have failed all standard curative and live prolonging therapy.
  • All subjects must have non-visceral metastatic disease localizations that are amenable to intra-tumor injection by clinical and ultrasound (US) guidance. These metastases should be amenable to a safe post-injection biopsy (partial or complete).
  • ECOG performance status of 0 or 1
  • Candidate for intralesional therapy defined as either one of the following: a) at least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion ≥ 10 mm in longest diameter, b) multiple injectable melanoma lesions that in aggregate have a longest diameter of ≥ 10 mm injectable disease
  • Adequate organ function determined within 28 days prior to enrollment, defined as follows: a) Hematological, i) Absolute neutrophil count ≥ 1500/mm3 (1.5x109/L) ii) Platelet count: ≥ 75.000/mm3 (7.5x109/L) iii) Hemoglobin: ≥ 8 g/dL (without need for hematopoietic growth factor or transfusion support) b) Renal, i) Serum creatinine: 1.5 x upper limit of normal (ULN), OR 24-hour creatinine clearance ≥ 60 mL/min for subject with creatinine levels > 1.5 x ULN. (Note: Creatinine clearance need not be determined if the baseline serum creatinine is within normal limits. Creatinine clearance should be calculated per institutional standard). c) Hepatic, i) Serum bilirubin: 1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total bilirubin level > 1.5 x ULN ii) Aspartate aminotransferase (AST): 2.5 x ULN OR ≤ 5 x ULN for subject with liver metastases iii) Alanine aminotransferase (ALT): 2.5 x ULN OR ≤ 5 x ULN for subject with liver metastases d) Coagulation, i) International normalization ratio (INR) or prothrombin time (PT): 1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and partial thromboplastin time (PTT)/ activated PTT (aPTT) is within therapeutic range of intended use of anticoagulants ii) PTT or aPTT: 1.5 x ULN unless the subject is receiving anticoagulant therapy as long as PT and PTT/aPTT is within therapeutic range of intended use of
  • Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to enrollment. If urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Subject has a tumor sample (archival sample obtained within 3 months prior to study participation or newly obtained biopsy). Subject must submit the tumor sample during screening. Subjects with a non-evaluable archival sample may obtain a new biopsy and subjects with a non-evaluable newly obtained biopsy may undergo re-biopsy at the discretion of the investigator.
  • Adequate vascular access to undergo a leucapheresis.

Exclusion Criteria:

  • Known active central nervous system (CNS) metastases. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids >10 mg/day of prednisone or equivalent. The exception does not include carcinomatosus meningitis which is excluded regardless of clinical stability.
  • History or evidence of active autoimmune disease that requires systemic treatment (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • History or evidence of melanoma associated with immunodeficiency states (e.g., hereditary immune deficiency, organ transplant, or leukemia)
  • History of other malignancy within the past 5 years with the following exceptions: i) Malignancy treated with curative intent and with no known active disease present and has not received chemotherapy for > 5 years before enrollment and felt to be at low risk for recurrence by the treating physician ii) Adequately treated non-melanoma skin cancer without evidence of disease at the time of enrollment iii) Adequately treated cervical carcinoma in situ without evidence of disease at the time of enrollment iv) Adequately treated breast ductal carcinoma in situ without evidence of disease at the time of enrollment v) Prostatic intraepithelial neoplasia without evidence of prostate cancer at the time of enrollment vi) Adequately treated superficial or in-situ carcinoma of the bladder without evidence of disease at the time of enrollment
  • Prior therapy with T-VEC or any other oncolytic viruses
  • Prior treatment of other tumor vaccine
  • Receive live vaccine within 28 days prior to enrollment
  • Prior chemotherapy, radiotherapy, biological cancer therapy, targeted therapy, or major surgery within 28 days prior to enrollment or has not recovered to CTCAE grade 1 or better from adverse event due to cancer therapy administered more than 28 days prior to enrollment.
  • Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study
  • Expected to require other cancer therapy while on study with the exception of local radiation treatment to the site of bone and other metastasis for palliative pain management
  • Other investigational procedures while participating in this study are excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03747744

Layout table for location information
UZ Brussel
Brussels, Belgium, 1090
Sponsors and Collaborators
Universitair Ziekenhuis Brussel
Layout table for investigator information
Principal Investigator: Bart Neyns, MD,PhD Universitair Ziekenhuis Brussel
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier: NCT03747744    
Other Study ID Numbers: 2017-BN-002
First Posted: November 20, 2018    Key Record Dates
Last Update Posted: December 29, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Talimogene laherparepvec
Antineoplastic Agents, Immunological
Antineoplastic Agents