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
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Safety and tolerability and recommended dose of CD137L-DC-EBV-VAX
Secondary Outcome
Activation of EBV-specific T cell responses
Condition
Nasopharyngeal Cancer
Intervention
CD137L-DC-EBV-VAX
Study Arms / Comparison Groups
locally recurrent or metastatic nasopharyngeal cancer
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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
55
Start Date
August 14, 2017
Completion Date
August 14, 2020
Primary Completion Date
August 14, 2019
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.
Gender
All
Ages
18 Years - 99 Years
Accepts Healthy Volunteers
No
Contacts
Boon Cher Goh, (65) 6779 5555, [email protected]
Location Countries
Singapore
Location Countries
Singapore
Administrative Informations
NCT ID
NCT03282617
Organization ID
NP01/03/16
Responsible Party
Sponsor
Study Sponsor
National University Hospital, Singapore
Study Sponsor
Boon Cher Goh, Principal Investigator, National University Hospital, Singapore
Verification Date
September 2017