Analyzing Childhood Recall Antigens in Patients With Pancreatic Cancer

Phase 2

Terminated

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.

Recruitment & Eligibility

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the pancreas
Patients is a candidate for gemcitabine chemotherapy (adjuvant, metastatic, locally advanced, borderline resectable settings all permitted)
Patients at least 18 years of age
ECOG performance status 0-2
Consent to donate 12 tubes of peripheral blood of 10 mL each
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
Ability to understand and willingness to sign a written informed consent document
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.
Patients may receive other concurrent chemotherapy, immunotherapy, or radiotherapy

Exclusion Criteria

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
Patients may not be receiving any investigational agents
Pregnant women
Patients with HIV

Arm && Interventions

Group	Intervention	Description
Gemcitabine with TT vaccine booster	Gemcitabine	Gemcitabine will be delivered as is standard of care. Patients diagnosed with pancreatic ductal carcinoma (PCD) will be treated with Gemcitabine and boosted once with the human childhood vaccine to TT
Gemcitabine with TT vaccine booster	TT vaccine booster	Gemcitabine will be delivered as is standard of care. Patients diagnosed with pancreatic ductal carcinoma (PCD) will be treated with Gemcitabine and boosted once with the human childhood vaccine to TT

Primary Outcome Measures

Name	Time	Method
Change in CD4 T Cell Responses Before TT Booster	Day 8	The relative difference in CD4 T cell counts before and after administration of the TT booster vaccine (Day 8) will be compared. The number of cells per microliter (cells/µL) will be determined. The proportion of at least 3-fold increase will be reported along with its 95% CI. The actual magnitude of change will be examined by taking a log scale of CD4 counts and report a mean of change on CD4 on its log scale along with its 95% CI.
Change in CD4 T Cell Responses After TT Booster	Day 28	The relative difference in CD4 T cell counts before and after administration of the TT booster vaccine (Day 8) will be compared. The number of cells per microliter (cells/µL) will be determined. The proportion of at least 3-fold increase will be reported along with its 95% CI. The actual magnitude of change will be examined by taking a log scale of CD4 counts and report a mean of change on CD4 on its log scale along with its 95% CI.

Secondary Outcome Measures

Name	Time	Method
Change in CD8 T Cell Responses Before TT Booster	Day 1	The relative difference in CD8 T cell counts before and after administration of the TT booster vaccine (Day 8) will be compared. The number of cells per microliter (cells/µL) will be determined. The proportion of at least 3-fold increase will be reported along with its 95% CI. The actual magnitude of change will be examined by taking a log scale of CD8 counts and report a mean of change on CD8 on its log scale along with its 95% CI.
Change in CD8 T Cell Responses Before TT Booster Vaccine	Day 8	The relative difference in CD8 T cell counts before and after administration of the TT booster vaccine (Day 8) will be compared. The number of cells per microliter (cells/µL) will be determined. The proportion of at least 3-fold increase will be reported along with its 95% CI. The actual magnitude of change will be examined by taking a log scale of CD8 counts and report a mean of change on CD8 on its log scale along with its 95% CI.
Change in CD8 T Cell Responses After TT Booster	Day 28	The relative difference in CD8 T cell counts before and after administration of the TT booster vaccine (Day 8) will be compared. The number of cells per microliter (cells/µL) will be determined. The proportion of at least 3-fold increase will be reported along with its 95% CI. The actual magnitude of change will be examined by taking a log scale of CD8 counts and report a mean of change on CD8 on its log scale along with its 95% CI.