Analyzing Childhood Recall Antigens in Patients With Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

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 public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Drug: Gemcitabine. Gemcitabine will be administered on days 1, 8, 15 every 28 days

Intervention public domain (ClinicalTrials.gov)

Biological: TT vaccine booster. One human TT childhood vaccine booster will be administered on day 8

Arm public domain (ClinicalTrials.gov)

Gemcitabine with TT vaccine booster (experimental): 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 public domain (ClinicalTrials.gov)

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. Time frame: Day 1.

Primary outcome public domain (ClinicalTrials.gov)

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. Time frame: Day 8.

Primary outcome public domain (ClinicalTrials.gov)

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. Time frame: Day 15.

Primary outcome public domain (ClinicalTrials.gov)

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. Time frame: Day 28.

Secondary outcome public domain (ClinicalTrials.gov)

Change in CD8 T Cell Responses Before TT Booster. Time frame: Day 1.

Secondary outcome public domain (ClinicalTrials.gov)

Change in CD8 T Cell Responses Before TT Booster Vaccine. Time frame: Day 8.

Secondary outcome public domain (ClinicalTrials.gov)

Change in CD8 T Cell Responses After TT Booster. Time frame: Day 15.

Secondary outcome public domain (ClinicalTrials.gov)

Change in CD8 T Cell Responses After TT Booster. Time frame: Day 28.

Eligibility public domain (ClinicalTrials.gov)

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

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 10 participants (actual).

Why stopped public domain (ClinicalTrials.gov)

Slow accrual

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Change in CD4 T Cell Responses Before TT Booster [Day 1]. Mean, cells/uL (Standard Deviation). Gemcitabine With TT Vaccine Booster (n=10): NA (NA) [Due to the condition of the blood samples analytical results were unable to be interpreted. As such, data is not available and mean CD4 T cell results have been identified as 'NA'.].

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Change in CD4 T Cell Responses Before TT Booster [Day 8]. Mean, cells/uL (Standard Deviation). Gemcitabine With TT Vaccine Booster (n=10): NA (NA) [Due to the condition of the blood samples analytical results were unable to be interpreted. As such, data is not available and mean CD4 T cell results have been identified as 'NA'.].

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Change in CD4 T Cell Responses After TT Booster [Day 15]. Mean, cells/uL (Standard Deviation). Gemcitabine With TT Vaccine Booster (n=10): NA (NA) [Due to the condition of the blood samples analytical results were unable to be interpreted. As such, data is not available and mean CD4 T cell results have been identified as 'NA'.].

Posted results (ClinicalTrials.gov registry) · primary outcome public domain (ClinicalTrials.gov)

Change in CD4 T Cell Responses After TT Booster [Day 28]. Mean, cells/uL (Standard Deviation). Gemcitabine With TT Vaccine Booster (n=10): NA (NA) [Due to the condition of the blood samples analytical results were unable to be interpreted. As such, data is not available and mean CD4 T cell results have been identified as 'NA'.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change in CD8 T Cell Responses Before TT Booster [Day 1]. Mean, cells/uL (Standard Deviation). Gemcitabine With TT Vaccine Booster (n=10): NA (NA) [Due to the condition of the blood samples analytical results were unable to be interpreted. As such, data is not available and mean CD4 T cell results have been identified as 'NA'.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change in CD8 T Cell Responses Before TT Booster Vaccine [Day 8]. Mean, cells/uL (Standard Deviation). Gemcitabine With TT Vaccine Booster (n=10): NA (NA) [Due to the condition of the blood samples analytical results were unable to be interpreted. As such, data is not available and mean CD4 T cell results have been identified as 'NA'.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change in CD8 T Cell Responses After TT Booster [Day 15]. Mean, cells/uL (Standard Deviation). Gemcitabine With TT Vaccine Booster (n=10): NA (NA) [Due to the condition of the blood samples analytical results were unable to be interpreted. As such, data is not available and mean CD4 T cell results have been identified as 'NA'.].

Posted results (ClinicalTrials.gov registry) · secondary outcome public domain (ClinicalTrials.gov)

Change in CD8 T Cell Responses After TT Booster [Day 28]. Mean, cells/uL (Standard Deviation). Gemcitabine With TT Vaccine Booster (n=10): NA (NA) [Due to the condition of the blood samples analytical results were unable to be interpreted. As such, data is not available and mean CD4 T cell results have been identified as 'NA'.].