Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Intratumoral Injection of Autologous CD1c (BDCA-1)+ myDC, Avelumab, and Ipilimumab Plus Systemic Nivolumab (myDAvIpNi)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03707808
Recruitment Status : Recruiting
First Posted : October 16, 2018
Last Update Posted : January 23, 2019
Sponsor:
Information provided by (Responsible Party):
Universitair Ziekenhuis Brussel

Brief Summary:
This phase I trial aims at investigating a new combinatorial immunotherapy regimen using intratumoral injection of autologous CD1c (BDCA-1)+ myeloid dendritic cells in combination with intratumoral injection of the CTLA-4 blocking monoclonal antibody (mAb) ipilimumab and the PD-L1 blocking mAb avelumab. Concomitantly, nivolumab (a PD-1 blocking mAb) will be administered intravenously.

Condition or disease Intervention/treatment Phase
Solid Tumor Metastases to Soft Tissue Drug: intratumoral injection of autologous CD1c (BDCA-1)+ myDC Phase 1

Detailed Description:

This phase I trial aims at investigating a new combinatorial immunotherapy regimen using intratumoral injection of autologous CD1c (BDCA-1)+ myeloid dendritic cells in combination with intratumoral injection of the CTLA-4 blocking monoclonal antibody (mAb) ipilimumab and the PD-L1 blocking mAb avelumab. Concomitantly, nivolumab (a PD-1 blocking mAb) will be administered intravenously.

CD1c (BDCA-1)+ myeloid dendritic (myDC) cells will be obtained by immunomagnetic isolation from PBMC obtained by leukapheresis. The CD1c (BDCA-1)+ myDC will not be substantially manipulated prior to autologous intratumoral injection, immediately following the isolation and concentration (isolation and administration will be performed in the same procedure). The investigators consider that the isolation represents a non-substantial manipulation of this somatic cell therapy product. The intended use of CD1c (BDCA-1)+ myDC in this clinical protocol is to enrich their presence within the injected metastasis where they should execute their physiological role of coordinating the anti-tumor immune response. Based on recent preclinical data, absence of myeloid dendritic cells in the tumor microenvironment is an important immune escape mechanism of malignant tumors.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial on Intratumoral Administration of Autologous CD1c (BDCA-1)+ Myeloid Dendritic Cells Plus Avelumab and Ipilimumab in Combination With Intravenously Administered Nivolumab
Actual Study Start Date : January 29, 2018
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine



Intervention Details:
  • Drug: intratumoral injection of autologous CD1c (BDCA-1)+ myDC
    intratumoral injections plus intravenous administration
    Other Names:
    • intratumoral injection of ipilimumab and avelumab
    • intravenous nivolumab


Primary Outcome Measures :
  1. Incidence and severity of Treatment-related Adverse Events graded according to CTCAE of intratumoral injection of autologous CD1c (BDCA-1)+ myDC plus avelumab and ipilimumab in combination with iv nivolumab [ Time Frame: 1 year ]
    Participants with treatment-related adverse events will be assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0


Secondary Outcome Measures :
  1. Objective response rate (ORR) of intratumoral injected CD1c (BDCA-1)+ myDC, avelumab, and ipilimumab plus iv nivolumab [ Time Frame: 1 year ]
    Objective response rate (ORR, defined as the percentage of subjects with a confirmed complete response (CR), or partial response at any time per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1



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
Criteria

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
  • Histologically confirmed advanced solid tumor that cannot be completely surgically resected
  • Failing all standard curative and live prolonging therapy.
  • Presence of skin- or lymphnode metastatic disease amenable to intratumoral injection by manual palpation, US or CT-guidance. At least one metastatic lesion should be amenable to a safe post-injection biopsy (by core needle biopsy, partial- or complete surgical resection).
  • ECOG performance status of 0 or 1
  • Candidate for intralesional therapy defined as either one of the following:
  • At least 1 injectable skin or lymph node metastatic lesion with a longest diameter of ≥ 10 mm
  • Multiple injectable tumor lesions that in aggregate have a longest diameter of ≥ 10 mm injectable disease
  • Adequate organ function determined within 14 days prior to enrollment, defined as follows:
  • Hematological: absolute neutrophil count ≥ 1500/mm3 (1.5x109/L), platelet count: ≥ 100.000/mm3 (7.5x109/L), hemoglobin: ≥ 9 g/dL (without need for hematopoietic growth factor or transfusion support)
  • Renal: 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).
  • Hepatic: serum bilirubin: 1.5 x ULN OR direct bilirubin ≤ ULN for a subject with total bilirubin level > 1.5 x ULN, aspartate aminotransferase (AST): 2.5 x ULN OR ≤ 5 x ULN for subject with liver metastases, alanine aminotransferase (ALT): 2.5 x ULN OR ≤ 5 x ULN for subject with liver metastases
  • Coagulation: 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, 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 anticoagulants
  • 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.
  • Availability of 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 >8 mg/day of methylprednisone 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 (eg, 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 immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia)
  • History of other malignancy within the past 5 years with the following exceptions: 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, adequately treated non-melanoma skin cancer without evidence of disease at the time of enrollment, adequately treated cervical carcinoma in situ without evidence of disease at the time of enrollment, adequately treated breast ductal carcinoma in situ without evidence of disease at the time of enrollment , prostatic intraepithelial neoplasia without evidence of prostate cancer at the time of enrollment, adequately treated superficial or in-situ carcinoma of the bladder without evidence of disease at the time of enrollment
  • Prior treatment of other tumor vaccine
  • 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.
  • History or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active autoimmune disease or syndrome that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy. 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.
  • Evidence of clinically significant immunosuppression such as the following: diagnosis of immunodeficiency, concurrent opportunistic infection, receiving systemic immunosuppressive therapy (> 2 weeks) or within 7 days prior to the first dose of study treatment, including oral steroid doses > 10 mg/day of prednisone or equivalent except for management of adverse events and central nervous system (CNS) metastases during the course of the study. Subjects that require intermittent use of bronchodilators or local steroid injection will not be excluded from the study.
  • Known human immunodeficiency virus (HIV) disease
  • Known acute or chronic hepatitis B or hepatitis C infection
  • Female subject is pregnant or breast-feeding, or planning to become pregnant during study treatment and through 3 months after the last dose of study treatment
  • Female subject of childbearing potential who is unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of study treatment. Note: Women not of childbearing potential are defined as: postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.) OR have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; OR has a congenital or acquired condition that prevents childbearing. Note: Acceptable methods of effective contraception are defined in the informed consent form.
  • Male subject unwilling to use acceptable method of effective contraception during trial participation and through 3 months after the last dose of study treatment. For this trial, male subjects will be considered to be of non-reproductive potential if they have azoospermia (whether due to having had a vasectomy or due to an underlying medical condition). Note: Acceptable methods of effective contraception are defined in the informed consent form.
  • Subject has known sensitivity to any of the products or components to be administered during dosing
  • Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the subject and investigator's knowledge
  • History or evidence of psychiatric, substance abuse, or any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
  • Is or has an immediate family member (eg, spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved in the this trial, unless prospective institutional review board (IRB)/independent ethics committee (IEC) approval (by chair or designee) is given allowing exception to this criterion for a specific subject
  • Sexually active subject who is unwilling to use a barrier method to avoid potential viral transmission during sexual contact during and within 3 months after study treatment.
  • Prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Subjects who have had a transplant > 5 years ago are eligible as long as there are no symptoms of Graft versus Host Disease.)
  • Known history of active Bacillus tuberculosis

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): NCT03707808


Contacts
Layout table for location contacts
Contact: Bart Neyns, MD, PhD +3224775447 bart.neyns@uzbrussel.be

Locations
Layout table for location information
Belgium
UZ Brussel Recruiting
Jette, Brabant, Belgium, 1090
Contact: Bart Neyns, Phd,Md    0032(0)2477 64 15    bart.neyns@uzbrussel.be   
Principal Investigator: Bart Neyns, Phd,Md         
Sponsors and Collaborators
Universitair Ziekenhuis Brussel
Layout table for additonal information
Responsible Party: Universitair Ziekenhuis Brussel
ClinicalTrials.gov Identifier: NCT03707808    
Other Study ID Numbers: 2017-BN-003
First Posted: October 16, 2018    Key Record Dates
Last Update Posted: January 23, 2019
Last Verified: January 2019
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
Keywords provided by Universitair Ziekenhuis Brussel:
solid tumors
Additional relevant MeSH terms:
Layout table for MeSH terms
Neoplasm Metastasis
Neoplastic Processes
Neoplasms
Pathologic Processes
Nivolumab
Ipilimumab
Antineoplastic Agents, Immunological
Antineoplastic Agents