Pancreatic Cancer
Conditions
Keywords
T-cell responses, Pancreatic cancer, Gemcitabine, Perforin, Granzyme-B, Myeloid-derived suppressor cells
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.
Interventions
DRUGGemcitabine
Gemcitabine will be administered on days 1, 8, 15 every 28 days
BIOLOGICALTT vaccine booster
One human TT childhood vaccine booster will be administered on day 8
Sponsors
Pancreatic Cancer Action Network
Albert Einstein College of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SCREENING
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CD4 T Cell Responses Before TT Booster | Day 1 | 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 15 | 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
| Measure | Time frame | Description |
|---|---|---|
| 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 15 | 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. |
Other
| Measure | Time frame |
|---|---|
| Change in Myeloid-derived Suppressor Cells | Day 8 |
Countries
United States
Participant flow
Pre-assignment details
Patients diagnosed with PDAC will be treated with Gemcitabine as is standard of care on days 1, 8, 15 every 28 days. On day 8 one booster with the human TT childhood vaccine will be administered. Blood will be drawn before each Gemcitabine treatment. On day 8, TT booster will be administered immediately after blood draw but at least 2 hours before Gemcitabine treatment. Patients who withdraw on or before Day 8 (before TT treatment) will not be included in data analysis.
Participants by arm
| Arm | Count |
|---|---|
| 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
Gemcitabine: Gemcitabine will be administered on days 1, 8, 15 every 28 days
TT vaccine booster: One human TT childhood vaccine booster will be administered on day 8 | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Gemcitabine With TT Vaccine Booster |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 74.3 years STANDARD_DEVIATION 9.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 2 Participants |
| Region of Enrollment United States | 10 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 2 / 10 |
Outcome results
Primary
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
Population: Blood samples were collected and analyzed by flow cytometry as well as by ELISPOT.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gemcitabine With TT Vaccine Booster | Change in CD4 T Cell Responses After TT Booster | NA cells/uL |
Primary
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
Population: Blood samples were collected and analyzed by flow cytometry as well as by ELISPOT.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gemcitabine With TT Vaccine Booster | Change in CD4 T Cell Responses After TT Booster | NA cells/uL |
Primary
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
Population: Blood samples were collected and analyzed by flow cytometry as well as by ELISPOT.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gemcitabine With TT Vaccine Booster | Change in CD4 T Cell Responses Before TT Booster | NA cells/uL |
Primary
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
Population: Blood samples were collected and analyzed from 10 patients by flow cytometry as well as by ELISPOT.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gemcitabine With TT Vaccine Booster | Change in CD4 T Cell Responses Before TT Booster | NA cells/uL |
Secondary
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.
Time frame: Day 15
Population: Blood samples were collected and analyzed by flow cytometry as well as by ELISPOT.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gemcitabine With TT Vaccine Booster | Change in CD8 T Cell Responses After TT Booster | NA cells/uL |
Secondary
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.
Time frame: Day 28
Population: Blood samples were collected and analyzed by flow cytometry as well as by ELISPOT.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gemcitabine With TT Vaccine Booster | Change in CD8 T Cell Responses After TT Booster | NA cells/uL |
Secondary
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.
Time frame: Day 1
Population: Blood samples were collected and analyzed by flow cytometry as well as by ELISPOT.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gemcitabine With TT Vaccine Booster | Change in CD8 T Cell Responses Before TT Booster | NA cells/uL |
Secondary
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.
Time frame: Day 8
Population: Blood samples were collected and analyzed by flow cytometry as well as by ELISPOT.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Gemcitabine With TT Vaccine Booster | Change in CD8 T Cell Responses Before TT Booster Vaccine | NA cells/uL |
Other Pre-specified
Change in Myeloid-derived Suppressor Cells
Time frame: Day 8
Population: MDSC data was not collected or analyzed for this study.