Pancreatic Cancer
Conditions
Keywords
Pancreatic Cancer, Immune-based therapies, CytotoxicT Lymphocytes
Brief summary
Status - CLOSED TO PATIENT ENROLLMENT (CNPE) Patients who have pancreatic cancer that has come back or has not gone away after treatment, including the standard treatment for this disease or patients who are not eligible for or have elected not to receive standard of care chemotherapy, and patients who will have surgery after treatment for pancreatic cancer are eligible for this study. This is a research study using special immune system cells called tumor-associated antigen (TAA)-specific cytotoxic T lymphocytes, a new experimental therapy. The proteins that are targeted in this study are called tumor-associated antigens (TAAs). These are cell proteins that are specific to the cancer cell. They do not show, or they show up in low quantities, on normal human cells. In this study, five common TAAs will be targeted. They are called NY-ESO-1, MAGEA4, PRAME, Survivin and SSX2. On a different study, patients have been treated and so far this treatment has shown to be safe. Investigators now want to try this treatment in patients with pancreatic cancer. These TAA-specific cytotoxic T lymphocytes (TAA-CTLs) are an investigational product not approved by the Food and Drug Administration. \*Arm A and Arm B are closed to new patient enrollment.\*
Detailed description
Status - CLOSED TO PATIENT ENROLLMENT (CNPE) The patient will give blood to make TAA-Specific cytotoxic T cells in a lab. These cells well be grown and frozen. If the TAA-Specific cytotoxic T cells can be made, the time from collection of the blood to manufacture of T cells for administration to the patient is about 1 to 2 months. The cells will be infused by intravenous infusion (IV) into the patient over 1-10 minutes. The patient may be pre-treated with acetaminophen (Tylenol) and diphenhydramine (Benadryl). Acetaminophen (Tylenol) and diphenhydramine (Benadryl) are given to prevent a possible allergic reaction to the TAA-CTL administration. Patients will be given up to six doses of TAA-CTLs at monthly intervals. The treatments will be given by the Center for Cell and Gene Therapy at Houston Methodist Hospital (HMH). MEDICAL TESTS BEFORE TREATMENT: * Physical exam. * Blood tests to measure blood cells, kidney and liver function. * Measurements of the patient's tumor by routine imaging studies and/or blood tests. The study will use the imaging study that was used before to follow the patient's tumor: CT, MRI, or PET. * Blood test to check for pregnancy for female patients who can have children MEDICAL TESTS DURING TREATMENT: Standard medical tests will be conducted on the day of the second and subsequent infusions: * Physical exams prior to each T cell infusion * Blood tests to measure blood cells, kidney and liver function. MEDICAL TESTS AFTER TREATMENT: \- Measurements the patient's tumor by routine imaging studies and/or blood tests done as per standard of care. To learn more about the way the TAA-CTLs are working in patient's body, an extra 20-40 mL (4-8 teaspoons) of blood will be taken before the infusion, at Weeks 1 and 2 after each infusion and at weeks 4, 6 and 8 and months 3, 6, 9 and 12 after the last infusion. The blood may be drawn from a central line at the time of the patient's regular blood tests. Investigators will use this blood to see how long the TAA-CTLs last, and to look at the immune system response to the patient's cancer. Study Duration: Patients will be active participants in this study for approximately one year after their last dose. Investigators will contact patients once a year for up to 4 additional years (total of 5 years follow-up) in order to evaluate disease response long-term. \*Arm A and Arm B are closed to new patient enrollment.\*
Interventions
BIOLOGICALmultiTAA specific T cells
Each patient will receive 6 infusions of multiTAA T cells at a fixed cell dose (1 x 10\^7 cells/m2) at the times specified in the group description. The expected volume of infusion will be 1 to 10 cc.
Sponsors
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital Research Institute
Pancreatic Cancer Action Network
The V Foundation for Cancer Research
Harris County Hospital District
Baylor College of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is designed as a fixed-dose pilot study to evaluate the safety and feasibility and efficacy of up to 6 intravenous infusions of multiTAA-specific T cells in pancreas cancer patients with metastatic, locally advanced unresectable, or resectable disease.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Status - CLOSED TO PATIENT ENROLLMENT (CNPE) Inclusion Criteria: PROCUREMENT: 1. Any patient with biopsy proven pancreatic adenocarcinoma. 2. Patients with life expectancy greater than or equal to 6 months. 3. Age greater than or equal to 18 years 4. Hgb greater than or equal to 7.0 g/dl (transfusions allowed) TREATMENT: 1. Any patient with biopsy-proven pancreatic adenocarcinoma: Group A: Patients with locally advanced or metastatic adenocarcinoma who are responding (defined as stable disease or tumor volume reduction) following 3 cycles of first line chemotherapy Group B: Patients with locally advanced or metastatic adenocarcinoma who have failed first line chemotherapy or are intolerant, ineligible or unwilling to receive standard of care chemotherapy Group C: Patients with resectable pancreatic cancer who have completed planned neo-adjuvant chemotherapy, radiotherapy or combination 2. Patients must have measurable or evaluable disease per RECIST 1.1 criteria. 3. Patients with life expectancy greater than or equal to 12 weeks 4. Age greater than or equal to 18 5. Pulse oximetry of greater than 95 percent on room air in patients who previously received radiation therapy 6. Patients with an ECOG score of ≤ 2 or Karnofsky score of 50 or greater 7. Patients with bilirubin less than or equal to 2x upper limit of normal, AST less than or equal to 3x upper limit of normal, Hgb greater than or equal to 7.0 g/dl (transfusion allowed). 8. Patients with a creatinine less than or equal to 2x upper limit of normal for age 9. Patients should have been off other investigational therapy for one month prior to receiving treatment on this study. 10. For Groups B or C patients must be off conventional therapy for at least 1 week prior to receiving treatment on this study. 11. Informed Consent explained to, understood by and signed by patient. Patient given copy of informed consent. 12. Due to unknown effects of this therapy on a fetus, pregnant women are excluded from this research. The male partner should use a condom. Females of child-bearing potential must be willing to utilize one of the more effective birth control methods during the study unless female has had a hysterectomy or tubal ligation.
Exclusion criteria
PROCUREMENT: 1. Patients with severe intercurrent infection. 2. Patients with active HIV infection (can be pending at this time) TREATMENT: 1. Patients with severe intercurrent infection. 2. Patients receiving systemic corticosteroids (Patients off steroids for at least 48 hours are eligible) 3. Pregnant 4. HIV positive
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Treatment Related Serious Adverse Events | 7 months | To determine the safety of up to 6 intravenous infusions of multiTAA-specific T cells in pancreatic cancer patients with metastatic, locally advanced unresectable, or resectable disease. |
| Number of Patients Who Received 6 Infusions of multiTAA-specific T Cells | 6 months | To determine the feasibility of completing a total of 6 intravenous infusions of multiTAA-specific T cells to pancreatic cancer patients with metastatic, locally advanced unresectable, or resectable disease |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Using the Kaplan-Meier Method | 5 years | To evaluate the progression-free of patients after multiTAA-specific T cell infusions. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and summarized with median survival times and 95% confidence intervals. PFS was defined as the time from the first infusion to the first occurrence of disease progression, relapse, or death from any cause. Patients without events were censored at the last follow-up date. |
| Overall Survival Using the Kaplan-Meier Method | 5 years | To evaluate the overall survival of patients after multiTAA-specific T cell infusions. Overall survival (OS) was estimated using the Kaplan-Meier method and summarized with median survival times and 95% confidence intervals. OS was defined as the time from the first infusion to death from any cause. Patients without events were censored at the last follow-up date. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group A Patients with locally advanced or metastatic pancreatic adenocarcinoma who are responding following 3 cycles of first line chemotherapy will receive 6 infusions with a fixed dose of multiTAA specific T cells beginning on the 4th week of the 4th cycle of chemotherapy. MultiTAA T cell infusions will occur on day 21 (a chemotherapy off week) of each chemotherapy cycle starting on chemotherapy cycle 4.
multiTAA specific T cells: Each patient will receive 6 infusions of multiTAA T cells at a fixed cell dose (1 x 10\^7 cells/m2) at the times specified in the group description. The expected volume of infusion will be 1 to 10 cc. | 13 |
| Group B Patients with locally advanced or metastatic pancreatic adenocarcinoma who have failed first line chemotherapy or are intolerant or ineligible to receive standard of care chemotherapy will be evaluated in the clinic and receive 6 infusions (administered at monthly intervals) with a fixed dose of multiTAA specific T cells.
multiTAA specific T cells: Each patient will receive 6 infusions of multiTAA T cells at a fixed cell dose (1 x 10\^7 cells/m2) at the times specified in the group description. The expected volume of infusion will be 1 to 10 cc. | 12 |
| Group C Patients with resectable pancreatic adenocarcinoma following completion of neoadjuvant chemotherapy, radiotherapy or combination. These patients will receive 6 infusions with a fixed dose of multiTAA specific T cells. One infusion will occur 4 weeks prior to surgical resection (with an option to infuse up to one week earlier) and after the completion of all pre-operative chemotherapy and/or radiation. The subsequent 5 infusions will occur at monthly intervals beginning 8 weeks post-surgery. Following surgery all patients will additionally receive 3 months of standard of care (SOC) chemotherapy starting week 9 after surgery. Hence, SOC chemo will occur weeks 9-11, 13-15, and 17-19 post-surgery and multiTAA T cell infusions will occur at weeks 8, 12, 16, 20, and 24 post-surgery.
multiTAA specific T cells: Each patient will receive 6 infusions of multiTAA T cells at a fixed cell dose (1 x 10\^7 cells/m2) at the times specified in the group description. The expected volume of infusion will be 1 to 10 cc. | 12 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 13 | 11 | 10 |
| Overall Study | Lost to Follow-up | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Group A | Group B | Group C | Total |
|---|---|---|---|---|
| Age, Continuous | 64 years | 51.5 years | 65 years | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 10 Participants | 9 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 10 Participants | 11 Participants | 32 Participants |
| Sex: Female, Male Female | 6 Participants | 6 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 7 Participants | 6 Participants | 4 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 13 / 13 | 11 / 12 | 10 / 12 |
| other Total, other adverse events | 13 / 13 | 12 / 12 | 11 / 12 |
| serious Total, serious adverse events | 4 / 13 | 6 / 12 | 3 / 12 |
Outcome results
Primary
Number of Patients Who Received 6 Infusions of multiTAA-specific T Cells
To determine the feasibility of completing a total of 6 intravenous infusions of multiTAA-specific T cells to pancreatic cancer patients with metastatic, locally advanced unresectable, or resectable disease
Time frame: 6 months
Population: Participants who received at least one infusion of multiTAA-specific T cells.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Number of Patients Who Received 6 Infusions of multiTAA-specific T Cells | 9 Participants |
| Group B | Number of Patients Who Received 6 Infusions of multiTAA-specific T Cells | 2 Participants |
| Group C | Number of Patients Who Received 6 Infusions of multiTAA-specific T Cells | 4 Participants |
Primary
Number of Patients With Treatment Related Serious Adverse Events
To determine the safety of up to 6 intravenous infusions of multiTAA-specific T cells in pancreatic cancer patients with metastatic, locally advanced unresectable, or resectable disease.
Time frame: 7 months
Population: Participants who received at least one infusion of multiTAA-specific T cells.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Group A | Number of Patients With Treatment Related Serious Adverse Events | 0 Participants |
| Group B | Number of Patients With Treatment Related Serious Adverse Events | 1 Participants |
| Group C | Number of Patients With Treatment Related Serious Adverse Events | 0 Participants |
Secondary
Overall Survival Using the Kaplan-Meier Method
To evaluate the overall survival of patients after multiTAA-specific T cell infusions. Overall survival (OS) was estimated using the Kaplan-Meier method and summarized with median survival times and 95% confidence intervals. OS was defined as the time from the first infusion to death from any cause. Patients without events were censored at the last follow-up date.
Time frame: 5 years
Population: The analysis population includes all participants who received at least one infusion of multiTAA-specific T cells.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Overall Survival Using the Kaplan-Meier Method | 14.1 months |
| Group B | Overall Survival Using the Kaplan-Meier Method | 4.4 months |
| Group C | Overall Survival Using the Kaplan-Meier Method | 12.6 months |
Secondary
Progression Free Survival Using the Kaplan-Meier Method
To evaluate the progression-free of patients after multiTAA-specific T cell infusions. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and summarized with median survival times and 95% confidence intervals. PFS was defined as the time from the first infusion to the first occurrence of disease progression, relapse, or death from any cause. Patients without events were censored at the last follow-up date.
Time frame: 5 years
Population: The analysis population includes all participants who received at least one infusion of multiTAA-specific T cells.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group A | Progression Free Survival Using the Kaplan-Meier Method | 6.4 months |
| Group B | Progression Free Survival Using the Kaplan-Meier Method | 2.2 months |
| Group C | Progression Free Survival Using the Kaplan-Meier Method | 7.5 months |