Clinical trial NCT03848182: Analyzing Childhood Recall Antigens in Patients With Pancreatic Cancer
Official title: Analysis of T Cells to Tetanus Toxoid Antigens in Patients With Pancreatic Cancer Treated With Gemcitabine
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Pancreatic Cancer
Keywords: T-cell responses
Pancreatic cancer
Gemcitabine
Perforin
Granzyme-B
Myeloid-derived suppressor cells
Lead sponsor: Albert Einstein College of Medicine
Sponsor class: OTHER
Collaborators: name: Pancreatic Cancer Action Network
First posted: 2019-02-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

Brief summary: The investigator is developing an immune therapy against pancreatic cancer. Immune cells, known as "T cells with tumor killing capacity", are involved in this immune therapy. In mice with pancreatic cance there is evidence that one tetanus toxoid (TT) vaccination (that patients receive from childhood) combined with Gemcitabine activates these killer T cells. (Gemcitabine improves T cell responses) These killer T cells are able to destroy tumor cells uploaded with TT protein (such studies are planned in future clinical trials). The goal of this study is to test whether one TT vaccination combined with Gemcitabine treatment activates the same T cells in pancreatic cancer patients.

Detailed description: Treating PDAC patients with gemcitabine and one TT booster Gemcitabine will be delivered as is standard of care. However, doses may be modified by the treating physician based on patient tolerance. Patients diagnosed with PDAC will be treated with Gemcitabine and boosted once with the human childhood vaccine to TT by Dr. Chuy as outlined in Fig 2. Gemcitabine will be administered on days 1, 8, 15 every 28 days, and one booster with the human TT childhood vaccine will be administered on day 8 (there must be 2 hrs between the TT booster and the Gemcitabine treatment). Blood will be drawn just before each Gemcitabine treatment, except on day 8 at least 2 hrs will be needed between the blood draw and Gemcitabine treatment because the TT booster needs to be given just after the blood draw but 2 hrs before the Gemcitabine treatment (Fig 2). Three tubes of 10 mls each with heparinized blood will be needed for the isolation of peripheral blood mononuclear cells (PBMC). Two tubes will be used to analyze the T cells and one tube for analyzing the MDSC. The memory T cells and MDSC will be analyzed in the laboratory of Dr. Gravekamp.

Eligibility criteria: Inclusion Criteria:

1. Histologically or cytologically confirmed adenocarcinoma of the pancreas
2. Patients is a candidate for gemcitabine chemotherapy (adjuvant, metastatic, locally advanced, borderline resectable settings all permitted)
3. Patients at least 18 years of age
4. ECOG performance status 0-2
5. Consent to donate 12 tubes of peripheral blood of 10 mL each
6. Adequate organ function as defined as -neutrophil count ≥ 1200 -platelets ≥ 75,000 -hemoglobin ≥ 8.0 -bilirubin ≤ 2.0 -creatinine ≤2.0 or calculated GFR ≥ 30
7. Ability to understand and willingness to sign a written informed consent document
8. Prior chemotherapy permitted, as long as 60 days have lapsed since last dose. Prior radiation therapy permitted, as long as 28 days lapsed since last treatment.
9. Patients may receive other concurrent chemotherapy, immunotherapy, or radiotherapy

Exclusion Criteria:

1. Patients never been immunized with tetanus toxoid (TT). Patients with a history of adverse reaction to tetanus vaccine (with the exception of self-limited fever or local tissue reaction
2. Patients may not be receiving any investigational agents
3. Pregnant women
4. Patients with HIV

Primary outcomes:
measure: Change in CD4 T Cell Responses Before TT Booster
timeFrame: Day 1
measure: Change in CD4 T Cell Responses Before TT Booster
timeFrame: Day 8
measure: Change in CD4 T Cell Responses After TT Booster
timeFrame: Day 15
measure: Change in CD4 T Cell Responses After TT Booster
timeFrame: Day 28
Secondary outcomes:
measure: Change in CD8 T Cell Responses Before TT Booster
timeFrame: Day 1
measure: Change in CD8 T Cell Responses Before TT Booster Vaccine
timeFrame: Day 8
measure: Change in CD8 T Cell Responses After TT Booster
timeFrame: Day 15
measure: Change in CD8 T Cell Responses After TT Booster
timeFrame: Day 28
Other outcomes:
measure: Change in Myeloid-derived Suppressor Cells
timeFrame: Day 8
Locations:
city: Bronx
country: United States
facility: Albert Einstein College of Medicine
state: New York
Study officials:
affiliation: Albert Einstein College of Medicine
name: Claudia Gravekamp, PhD
role: PRINCIPAL_INVESTIGATOR
References: