This phase I pilot trial studies the side effects of cluster of differentiation 8 (CD8)+ T
cells in treating patients with gastrointestinal tumors that have spread to other places in
the body. Tumor cells and blood are used to help create an adoptive T cell therapy, such as
CD8+ T cell therapy, that is individually designed for a patient and may help doctors learn
more about genetic changes in the tumor. Immunotherapy with monoclonal antibodies, such as
pembrolizumab, may help the body's immune system attack the cancer, and may interfere with
the ability of tumor cells to grow and spread. Giving CD8+ T cell therapy and pembrolizumab
may work better in treating patients with gastrointestinal tumors.
PRIMARY OBJECTIVES:
I. Assess the safety of using a personalized adoptive T cell therapy in patients with
advanced gastrointestinal malignancies.
SECONDARY OBJECTIVES:
I. Assess the persistence of an immune response after T cell infusion. II. Determine the
clinical benefit of adoptive T cell therapy in advanced gastrointestinal cancers.
OUTLINE:
Beginning 2 days prior to CD8+ T cell infusion, patients receive cyclophosphamide
intravenously (IV) over 30 minutes. Patients undergo CD8+ T cell infusion IV over 2 hours on
day 0 and receive aldesleukin subcutaneously (SC) twice daily (BID) on days 1-14. Beginning
on day 1 about 24 hours after CD8+ T cell infusion, patients receive pembrolizumab IV over
30-60 minutes on weeks 3, 6, 12, and 15.
After completion of study treatment, patients are followed up for 24 weeks.
Inclusion Criteria:
- Histopathologic documentation of pancreatic adenocarcinoma, colorectal adenocarcinoma,
cholangiocarcinoma, esophageal cancer and gastric cancer with radiographic evidence of
metastatic disease
- Eastern Cooperative Oncology Group (ECOG)/Zubrod performance status of 0 or 1
- Women of childbearing potential (WOCBP) must be using an adequate method of
contraception to avoid pregnancy throughout the study in such a manner that the risk
of pregnancy is minimized; suggested precautions should be used to minimize the risk
or pregnancy for at least 1 month before start of therapy, and while women are on
study for at least 8 weeks after pembrolizumab is stopped; WOCBP include any female
who has experienced menarche and who has not undergone successful surgical
sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is
not postmenopausal; acceptable forms of birth control include condom, diaphragm,
hormonal, intrauterine device (IUD), or sponge plus spermicide; abstinence is also an
acceptable form of birth control
- Men must be willing and able to use an acceptable method of birth control, during and
for at least 3 months after completion of the study, if their sexual partners are
WOCBP
- Willing and able to give informed consent
- Adequate vein access: consider peripherally inserted central catheter (PICC) or other
central line
- Patients must have adequate tissue (fresh or frozen) available or planned removal of
adequate tissue for analysis; at least 250 mg of tumor are needed for peptide elution;
there is no specific time limit on how long the tissue can remain frozen prior to use
- Patients can have any lines (including zero) of prior therapy to sign consent prior to
tissue harvest
- Toxicity related to prior therapy must either have returned to =< grade 1, baseline,
or been deemed irreversible
- ELIGIBILITY FOR TREATMENT: ECOG/Zubrod performance status of 0 to 2
- Bi-dimensionally measurable disease by radiographic imaging (computed tomography [CT]
scan) that represents at least one measurable lesion per Response Evaluation Criteria
in Solid Tumors (RECIST) version (v)1.1
- At least 4 weeks must have elapsed since the last chemotherapy, radiotherapy or major
surgery
- Toxicity related to prior therapy must either have returned to less than or equal to
grade 1, baseline, or been deemed irreversible
- Subjects must have received at least one line of chemotherapy prior to receiving
adoptive T cell therapy and should have exhausted standard of care systemic therapy
options; the decision to implement the T cell therapy will be at the discretion of the
treating physician; the timing and total exposure to chemotherapy will depend on the
tumor type in question (more systemic options for breast cancer; fewer for gastric
cancer, for example); due to the heterogeneity of tumors being treated in this
protocol, the discretion of the treating physician in terms of timing of immunotherapy
will be critical
Exclusion Criteria:
- EXCLUSION FOR ENROLLMENT: Any other malignancy from which the patient has been
disease-free for less than 5 years, with the exception of adequately treated and cured
basal or squamous cell skin cancer, superficial bladder cancer, and carcinoma in situ
of the cervix
- Pregnant women, nursing mothers, men or women of reproductive ability who are
unwilling to use effective contraception; women of childbearing potential with a
positive pregnancy test within 3 days prior to entry
- Significant cardiovascular abnormalities as defined by any one of the following:
- Congestive heart failure New York Heart Association (NYHA) classes II-IV;
patients with asymptomatic class I congestive heart failure (CHF) may participate
in conjunction with a cardiology consultation
- Clinically significant hypotension
- Symptoms of coronary artery disease
- Presence of arrhythmias in electrocardiography (EKG) requiring drug therapy
- Active and untreated central nervous system (CNS) metastases (including metastasis
identified during screening MRI or contrast CT); patients with asymptomatic, treated
metastases may be eligible if their lesion(s) have demonstrated stability over 2
months
- Autoimmune disease: patients with a history of inflammatory bowel disease are excluded
from this study, as are patients with a history of autoimmune disease (e.g. systemic
lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression
during treatment would be considered by the investigator to be unacceptable
- Any underlying medical or psychiatric condition, which in the opinion of the
investigator, will make the administration of study drug hazardous or obscure the
interpretation of adverse events, such as a condition associated with frequent
diarrhea
- White blood cell (WBC) less than or equal to 2000/uL
- Hematocrit (Hct) less than or equal to 24% or hemoglobin (Hgb) less than or equal to 8
g/dL
- Absolute neutrophil count (ANC) less than or equal to 1000
- Platelets less than or equal to 75,000
- Creatinine greater than or equal to 1.5 x upper limit of normal (ULN) OR creatinine
clearance > 50 ml/min/1.73 m^2 for patients with creatinine levels above institutional
normal limits
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) greater than or equal
to 2.5 x ULN
- Bilirubin greater than or equal to 2.0 x ULN
- Positive screening tests for human immunodeficiency virus (HIV), hepatitis (Hep) B,
and Hep C; if positive results are not indicative of true active or chronic infection,
the patient can be treated
- EXCLUSION CRITERIA FOR TREATMENT: WBC less than or equal to 2000/uL
- EXCLUSION CRITERIA FOR TREATMENT: Hct less than or equal to 24%
- EXCLUSION CRITERIA FOR TREATMENT: Hgb less than or equal to 8 g/dL
- EXCLUSION CRITERIA FOR TREATMENT: ANC less than or equal to 1000
- EXCLUSION CRITERIA FOR TREATMENT: Platelets less than or equal to 75,000
- EXCLUSION CRITERIA FOR TREATMENT: Creatinine greater than or equal to 1.5 x ULN OR
creatinine clearance > 50 ml/min/1.73m^2 for patients with creatinine levels above
institutional normal limits
- EXCLUSION CRITERIA FOR TREATMENT: AST/ALT greater than or equal to 2.5 x ULN
- EXCLUSION CRITERIA FOR TREATMENT: Bilirubin greater than or equal to 2.0 x ULN
- Steroids are not permitted 3 days prior to T cell infusion and concurrently during
therapy
- Uncontrolled concurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements
- Any non-oncology vaccine therapy used for the prevention of infectious disease within
1 month before or after any anti-programmed cell death protein 1 (PD1) monoclonal
antibody (anti-PD-1) dose
- After the T cell infusion, patients may not be on any other treatments for their
cancer aside from those included in the treatment section of the protocol
- Coagulation 1.5 x ULN unless participant is receiving anticoagulant therapy as long as
prothrombin time (PT) or a partial thromboplastin time (PTT) is within therapeutic
range of intended use of anticoagulants