Analyzing Childhood Recall Antigens in Patients With Pancreatic Cancer

Analysis of T Cells to Tetanus Toxoid Antigens in Patients With Pancreatic Cancer Treated With Gemcitabine

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.

Study Overview

• Status: Terminated
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: Gemcitabine; Biological: TT vaccine booster

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.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Albert Einstein College Of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Gemcitabine with 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	Drug: Gemcitabine; Gemcitabine will be administered on days 1, 8, 15 every 28 days; Other Names: Gemzar; Biological: TT vaccine booster; One human TT childhood vaccine booster will be administered on day 8; Other Names: Tetanus vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CD4 T Cell Responses Before TT Booster	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.	Day 1
Change in CD4 T Cell Responses Before TT Booster	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.	Day 8
Change in CD4 T Cell Responses After TT Booster	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.	Day 15
Change in CD4 T Cell Responses After TT Booster	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.	Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CD8 T Cell Responses Before TT Booster	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.	Day 1
Change in CD8 T Cell Responses Before TT Booster Vaccine	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.	Day 8
Change in CD8 T Cell Responses After TT Booster	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.	Day 15
Change in CD8 T Cell Responses After TT Booster	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.	Day 28

Other Outcome Measures

Outcome Measure	Time Frame
Change in Myeloid-derived Suppressor Cells	Day 8

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: Pancreatic Cancer Action Network
• Investigators: Principal Investigator: Claudia Gravekamp, PhD, Albert Einstein College Of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2017
• Primary Completion (Actual): November 23, 2018
• Study Completion (Actual): November 11, 2019

Study Registration Dates

• First Submitted: February 19, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): April 18, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Gemcitabine; Pancreatic cancer; T-cell responses; Perforin; Granzyme-B; Myeloid-derived suppressor cells
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunologic Factors; Vaccines; Gemcitabine
• Other Study ID Numbers: 2016-7197; 422247 (Other Grant/Funding Number: Pancreatic Cancer Action Network)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes