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.
Brief Title
Analyzing Childhood Recall Antigens in Patients With Pancreatic Cancer
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Pancreatic Cancer
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
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
Inclusion 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
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
Gender
All
Gender Based
false
Keywords
T-cell responses
Pancreatic cancer
Gemcitabine
Perforin
Granzyme-B
Myeloid-derived suppressor cells
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
100 Years
Minimum Age
18 Years
NCT Id
NCT03848182
Org Class
Other
Org Full Name
Albert Einstein College of Medicine
Org Study Id
2016-7197
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
Analysis of T Cells to Tetanus Toxoid Antigens in Patients With Pancreatic Cancer Treated With Gemcitabine
Primary Outcomes
Outcome Description
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.
Outcome Measure
Change in CD4 T Cell Responses Before TT Booster
Outcome Time Frame
Day 1
Outcome Description
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.
Outcome Measure
Change in CD4 T Cell Responses Before TT Booster
Outcome Time Frame
Day 8
Outcome Description
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.
Outcome Measure
Change in CD4 T Cell Responses After TT Booster
Outcome Time Frame
Day 15
Outcome Description
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.
Outcome Measure
Change in CD4 T Cell Responses After TT Booster
Outcome Time Frame
Day 28
Secondary Ids
Secondary Id
422247
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
Day 1
Outcome Measure
Change in CD8 T Cell Responses Before TT Booster
Outcome Description
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.
Outcome Time Frame
Day 8
Outcome Measure
Change in CD8 T Cell Responses Before TT Booster Vaccine
Outcome Description
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.
Outcome Time Frame
Day 15
Outcome Measure
Change in CD8 T Cell Responses After TT Booster
Outcome Description
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.
Outcome Time Frame
Day 28
Outcome Measure
Change in CD8 T Cell Responses After TT Booster
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
100
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Claudia Gravekamp
Investigator Email
claudia.gravekamp@einsteinmed.org
Investigator Phone
718-430-4048