TAA Specific Cytotoxic T Lymphocytes in Patients With Pancreatic Cancer (TACTOPS)

• ClinicalTrials.gov Identifier: NCT03192462
• Recruitment Status: Active, not recruiting
• First Posted: June 20, 2017
• Last Update Posted: May 28, 2020
• Sponsor: Baylor College of Medicine
• Collaborators: Center for Cell and Gene Therapy, Baylor College of Medicine; The Methodist Hospital System; Pancreatic Cancer Action Network; The V Foundation for Cancer Research; Harris County Hospital District
• Information provided by (Responsible Party): Benjamin Leon Musher, Baylor College of Medicine

Study Description

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.*

Condition or disease	Intervention/treatment	Phase
Pancreatic Cancer	Biological: multiTAA specific T cells	Phase 1; Phase 2

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.*

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Tumor-Associated Antigen (TAA) Specific Cytotoxic T Lymphocytes Administered in Patients With Pancreatic Cancer
• Actual Study Start Date: January 18, 2018
• Estimated Primary Completion Date: May 1, 2021
• Estimated Study Completion Date: November 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group A (Closed to New Patient Enrollment); 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.	Biological: 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.
Experimental: Group B (Closed to New Patient Enrollment); 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.	Biological: 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.
Experimental: Group C (Closed to New Patient Enrollment); 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.	Biological: 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.

Outcome Measures

Primary Outcome Measures :

1. Number of patients with treatment related serious adverse events [ Time Frame: 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.
2. Number of patients who received 6 infusions of multiTAA-specific T cells [ Time Frame: 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 Outcome Measures :

1. Progression Free Survival using the Kaplan-Meier method [ Time Frame: 5 years ]
   To evaluate the progression-free of patients after multiTAA-specific T cell infusions
2. Overall Survival using the Kaplan-Meier method [ Time Frame: 5 years ]
   To evaluate the overall survival of patients after multiTAA-specific T cell infusions

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Texas

Baylor Clinic

Houston, Texas, United States, 77030

Houston Methodist Hospital

Houston, Texas, United States, 77030

Harris Health System - Smith Clinic

Houston, Texas, United States, 77054

Sponsors and Collaborators

Baylor College of Medicine

Center for Cell and Gene Therapy, Baylor College of Medicine

The Methodist Hospital System

Pancreatic Cancer Action Network

The V Foundation for Cancer Research

Harris County Hospital District

Investigators

• Principal Investigator: Anne Leen, PhD; Baylor College of Medicine
• Principal Investigator: Benjamin Musher, MD; Baylor College of Medicine

More Information

• Responsible Party: Benjamin Leon Musher, Assistant Professor, Baylor College of Medicine
• ClinicalTrials.gov Identifier: NCT03192462
• Other Study ID Numbers: H-40378 TACTOPS
• First Posted: June 20, 2017
• Last Update Posted: May 28, 2020
• Last Verified: May 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Benjamin Leon Musher, Baylor College of Medicine:

Pancreatic Cancer; Immune-based therapies; CytotoxicT Lymphocytes

Additional relevant MeSH terms:

Pancreatic Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases