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Dendritic Cell Therapy With CD137L-DC-EBV-VAX in Locally Advanced Stage IV or Locally Recurrent/Metastatic Nasopharyngeal Carcinoma

Primary Purpose

Nasopharyngeal Cancer

Status
Unknown status
Phase
Phase 1
Locations
Singapore
Study Type
Interventional
Intervention
CD137L-DC-EBV-VAX
Sponsored by
National University Hospital, Singapore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Nasopharyngeal Cancer

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Eligibility Criteria:

  • Age ≥ 18 year
  • Ability to understand and the willingness to sign a written informed consent document.
  • 2 cohorts of patients are eligible for the study: Cohort A - Histologically or cytologically confirmed non-keratinizing nasopharyngeal carcinoma (NPC) that has recurred at locoregional and/or distant sites. Patients must have just received at least 1 cycle of chemotherapy and achieved stable disease, partial or complete response.

Cohort B - Histologically or cytologically confirmed stage 4A/B (locally advanced) non-keratinizing NPC that has just completed concurrent chemoradiotherapy less than 2 months before study entry.

  • Measurable disease according to the RECIST criteria (version 1.1) is not necessary, but tumor assessments on follow up will be according to RECIST criteria (version 1.1) as defined in section 11 for the evaluation of disease.
  • Archived or fresh tumor sample available. Willingness to donate blood and tissue for mandatory correlative research studies (see Section 9).
  • ECOG performance status of 0, 1 or 2 (see Appendix A).
  • Patients must have adequate organ and marrow function as defined below:

    • Absolute monocyte count ≥0.2 x 109/L
    • Platelets ≥100 x109/L
    • Hemoglobin ≥8.0 g/dL
    • Serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase, [SGPT]) < 2.5 x upper limit of normal (ULN), OR < 5 x ULN in the presence of liver metastases.
    • Serum total bilirubin < 2 x ULN (except patients with Gilbert Syndrome, who can have total bilirubin <3.0 mg/dL)
    • Serum creatinine < 1.5 x ULN

Exclusion Criteria:

- Any of the following:

  • Chemotherapy ≤ 4 weeks prior to CD137L-DC-EBV-VAX study treatment.
  • Radiotherapy ≤ 4 weeks prior to CD137L-DC-EBV-VAX study treatment.
  • Nitrosoureas or Mitomycin C ≤ 4 weeks prior to registration

NOTE: Prior palliative radiotherapy to bone metastases is allowed ≤ 4 weeks prior to registration. Prior immunotherapy with immune checkpoint inhibitors will not be allowed.

  • Prior investigational agents ≤ 4 weeks prior to registration.
  • Known allergy to Tetanus and/or Diphtheria toxoid.
  • Known brain metastases or leptomeningeal metastases. NOTE: symptomatic, and/or if they require immunosuppressive doses of corticosteroids (e.g. >10 mg/day prednisone or equivalents) for at least 2 weeks prior to study drug administration. Patients with treated brain metastases who are deemed clinically stable and without radiological progression on PET, MRI or CT scan performed ≤ 8 weeks of study entry, are not excluded. NOTE: Primary nasopharyngeal cancers that directly invade the skull base and extend into the infratemporal fossa(e) are not regarded as brain metastases and are not excluded.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception
  • Active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. NOTE: These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as SLE, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.
  • Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event).
  • Condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if <10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.

Sites / Locations

  • National University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

locally recurrent or metastatic nasopharyngeal cancer

stage 4 locally advanced nasopharyngeal cancer

Arm Description

This cohort consists of patients with metastatic or locally recurrent NPC who have received systemic concurrent chemotherapy and have a favourable response of stable disease, partial or complete response. As up to 30% of these patients will suffer from relapse within 5 months of completion of chemotherapy, following definitive treatment, y, and treatment with CD137L-DC-EBV-VAX may activate T cell response against the tumor and prolong time to progression.

This cohort consists of patients with stage 4 locally advanced patients (N2 and N3 disease, and/or T4 disease) who are treated definitely with chemoradiation with curative intent, but who have a high risk of distant relapse. Treatment with CD137L-DC-EBV-VAX may activate antitumor T cell responses and prolong time to relapse.

Outcomes

Primary Outcome Measures

Safety and tolerability and recommended dose of CD137L-DC-EBV-VAX

Secondary Outcome Measures

Activation of EBV-specific T cell responses
Antitumor Effect based on Immune Response Criteria (IRC)
Progression-free survival and overall survival

Full Information

First Posted
September 12, 2017
Last Updated
September 12, 2017
Sponsor
National University Hospital, Singapore
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1. Study Identification

Unique Protocol Identification Number
NCT03282617
Brief Title
Dendritic Cell Therapy With CD137L-DC-EBV-VAX in Locally Advanced Stage IV or Locally Recurrent/Metastatic Nasopharyngeal Carcinoma
Official Title
Dendritic Cell Therapy With CD137L-DC-EBV-VAX in Locally Advanced Stage IV or Locally Recurrent/Metastatic Nasopharyngeal Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Unknown status
Study Start Date
August 14, 2017 (Actual)
Primary Completion Date
August 14, 2019 (Anticipated)
Study Completion Date
August 14, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National University Hospital, Singapore

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is carried out to find out the safety and recommended dose of CD137L-DC-EBV-VAX in nasopharyngeal cancer. CD137L-DC-EBV-VAX is a product made from one of our own immune system cells (dendritic cell, DC). Dendritic cells are immune cells that help to stimulate our body's T lymphocytes to fight cancer by presenting specific proteins from the cancer cells. The investigators have developed in the laboratory a highly effective dendritic cell which is primed to activate T cells with the Epstein-Barr virus (EBV) proteins. It is hoped that this will stir an immune response to recognize NPC cells and kill them as part of body's immune surveillance system.
Detailed Description
This study will involve two cohorts of patients, A and B. Patients are invited because they have either (A) locally recurrent or metastatic nasopharyngeal cancer; or (B) stage 4 locally advanced nasopharyngeal cancer (N2 or N3 disease and/or T4) and is known to be associated with a high risk of distant relapse. This study is carried out to find out the safety and recommended dose of CD137L-DC-EBV-VAX in nasopharyngeal cancer. CD137L-DC-EBV-VAX is a product made from one of our own immune system cells (dendritic cell, DC). Dendritic cells are immune cells that help to stimulate our body's T lymphocytes to fight cancer by presenting specific proteins from the cancer cells. The investigators have developed in the laboratory a highly effective dendritic cell which is primed to activate T cells with the Epstein-Barr virus (EBV) proteins. It is hoped that this will stir an immune response to recognize NPC cells and kill them as part of body's immune surveillance system.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
Patients will be given CD137L-DC-EBV-VAX for about 5 - 7 times and be followed up until a maximum of 3 years from study entry.
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
locally recurrent or metastatic nasopharyngeal cancer
Arm Type
Experimental
Arm Description
This cohort consists of patients with metastatic or locally recurrent NPC who have received systemic concurrent chemotherapy and have a favourable response of stable disease, partial or complete response. As up to 30% of these patients will suffer from relapse within 5 months of completion of chemotherapy, following definitive treatment, y, and treatment with CD137L-DC-EBV-VAX may activate T cell response against the tumor and prolong time to progression.
Arm Title
stage 4 locally advanced nasopharyngeal cancer
Arm Type
Experimental
Arm Description
This cohort consists of patients with stage 4 locally advanced patients (N2 and N3 disease, and/or T4 disease) who are treated definitely with chemoradiation with curative intent, but who have a high risk of distant relapse. Treatment with CD137L-DC-EBV-VAX may activate antitumor T cell responses and prolong time to relapse.
Intervention Type
Biological
Intervention Name(s)
CD137L-DC-EBV-VAX
Other Intervention Name(s)
Dendritic cell therapy
Intervention Description
Patients will receive CD137L-DC-EBV-VAX at a dose of approximately 5-50 millioncells every 2 weeks, for a total of 5-7 times.
Primary Outcome Measure Information:
Title
Safety and tolerability and recommended dose of CD137L-DC-EBV-VAX
Time Frame
From the start of assessment until study completion, an average of 3 year
Secondary Outcome Measure Information:
Title
Activation of EBV-specific T cell responses
Time Frame
From the start of assessment until study completion, an average of 3 year
Title
Antitumor Effect based on Immune Response Criteria (IRC)
Time Frame
From the start of assessment until study completion, an average of 3 year
Title
Progression-free survival and overall survival
Time Frame
From the start of assessment until study completion, an average of 3 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Eligibility Criteria: Age ≥ 18 year Ability to understand and the willingness to sign a written informed consent document. 2 cohorts of patients are eligible for the study: Cohort A - Histologically or cytologically confirmed non-keratinizing nasopharyngeal carcinoma (NPC) that has recurred at locoregional and/or distant sites. Patients must have just received at least 1 cycle of chemotherapy and achieved stable disease, partial or complete response. Cohort B - Histologically or cytologically confirmed stage 4A/B (locally advanced) non-keratinizing NPC that has just completed concurrent chemoradiotherapy less than 2 months before study entry. Measurable disease according to the RECIST criteria (version 1.1) is not necessary, but tumor assessments on follow up will be according to RECIST criteria (version 1.1) as defined in section 11 for the evaluation of disease. Archived or fresh tumor sample available. Willingness to donate blood and tissue for mandatory correlative research studies (see Section 9). ECOG performance status of 0, 1 or 2 (see Appendix A). Patients must have adequate organ and marrow function as defined below: Absolute monocyte count ≥0.2 x 109/L Platelets ≥100 x109/L Hemoglobin ≥8.0 g/dL Serum alanine aminotransferase (ALT; serum glutamate-pyruvate transferase, [SGPT]) < 2.5 x upper limit of normal (ULN), OR < 5 x ULN in the presence of liver metastases. Serum total bilirubin < 2 x ULN (except patients with Gilbert Syndrome, who can have total bilirubin <3.0 mg/dL) Serum creatinine < 1.5 x ULN Exclusion Criteria: - Any of the following: Chemotherapy ≤ 4 weeks prior to CD137L-DC-EBV-VAX study treatment. Radiotherapy ≤ 4 weeks prior to CD137L-DC-EBV-VAX study treatment. Nitrosoureas or Mitomycin C ≤ 4 weeks prior to registration NOTE: Prior palliative radiotherapy to bone metastases is allowed ≤ 4 weeks prior to registration. Prior immunotherapy with immune checkpoint inhibitors will not be allowed. Prior investigational agents ≤ 4 weeks prior to registration. Known allergy to Tetanus and/or Diphtheria toxoid. Known brain metastases or leptomeningeal metastases. NOTE: symptomatic, and/or if they require immunosuppressive doses of corticosteroids (e.g. >10 mg/day prednisone or equivalents) for at least 2 weeks prior to study drug administration. Patients with treated brain metastases who are deemed clinically stable and without radiological progression on PET, MRI or CT scan performed ≤ 8 weeks of study entry, are not excluded. NOTE: Primary nasopharyngeal cancers that directly invade the skull base and extend into the infratemporal fossa(e) are not regarded as brain metastases and are not excluded. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Any of the following: Pregnant women Nursing women Men or women of childbearing potential who are unwilling to employ adequate contraception Active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids. NOTE: These include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as SLE, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease. Patients with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible. Patients with rheumatoid arthritis and other arthropathies, Sjögren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible. Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event). Condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses <10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). Physiologic replacement doses of systemic corticosteroids are permitted, even if <10 mg/day prednisone equivalents. A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Boon Cher Goh
Phone
(65) 6779 5555
Email
phcgbc@nus.edu.sg
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boon Cher Goh
Organizational Affiliation
National University Hospital, Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
National University Hospital
City
Singapore
Country
Singapore
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Boon Cher Goh, MBBS, MRCP
Phone
65-6772-4617
Email
Boon_Cher_Goh@nuhs.com.sg
First Name & Middle Initial & Last Name & Degree
Boon Cher Goh, MBBS, MRCP

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25769204
Citation
Petersson F. Nasopharyngeal carcinoma: a review. Semin Diagn Pathol. 2015 Jan;32(1):54-73. doi: 10.1053/j.semdp.2015.02.021. Epub 2015 Feb 25.
Results Reference
background
PubMed Identifier
26351355
Citation
Lee AW, Ma BB, Ng WT, Chan AT. Management of Nasopharyngeal Carcinoma: Current Practice and Future Perspective. J Clin Oncol. 2015 Oct 10;33(29):3356-64. doi: 10.1200/JCO.2015.60.9347. Epub 2015 Sep 8.
Results Reference
background
PubMed Identifier
12450728
Citation
Yu MC, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 2002 Dec;12(6):421-9. doi: 10.1016/s1044579x02000858.
Results Reference
background

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Dendritic Cell Therapy With CD137L-DC-EBV-VAX in Locally Advanced Stage IV or Locally Recurrent/Metastatic Nasopharyngeal Carcinoma

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