Cell Therapy (Tumor Infiltrating Lymphocytes) and Aldesleukin in Treating Patients with Locally Advanced, Recurrent, Refractory, or Metastatic Biliary Tract Cancers
This phase II trial studies how well tumor infiltrating lymphocytes and aldesleukin work in treating patients with biliary tract cancers that has spread to other places in the body, has come back, or does not respond to treatment. Tumor infiltrating lymphocytes are a type of white blood cells which are taken from patients' tumors, grown in the laboratory in large numbers, and then given back to the patient to fight the tumor. Before receiving the cells, chemotherapy drugs called cyclophosphamide and fludarabine are given to temporarily suppress the immune system to improve the chances that the tumor fighting cells will be able to survive in the body. After the cells are given, aldesleukin may help the tumor fighting cells stay alive longer. This study is being done to see if giving tumor infiltrating lymphocytes and aldesleukin will cause biliary tract tumors to shrink.
- Measurable locally advanced, recurrent, or metastatic biliary tract carcinoma (including intrahepatic or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary carcinoma).
- Patients with locally advanced disease should be unresectable by conventional surgical approaches.
- Patients with distant metastatic spread must be refractory to approved standard systemic therapies (such as gemcitabine, cisplatin, or equivalents) if they are eligible to receive these treatments.
- Patients must be co-enrolled on the companion protocol HCC 17-220 (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre- Clinical Studies) and have available TIL cultures for therapy.
- Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
- Able to understand and sign the informed consent document.
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Life expectancy of greater than three months.
- Patients of both genders who are of child-bearing potential must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the treatment.
- Serology: * Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.) * Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative.
- Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
- Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
- White blood cells (WBC) >= 3000/mm^3.
- Platelet count >= 100,000/mm^3.
- Hemoglobin > 8.0 g/dl.
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< to 3.5 times the upper limit of normal.
- Serum creatinine =< to 1.6 mg/dl.
- Total bilirubin =< to 2.0 mg/dl, except in patients with Gilbert’s syndrome who must have a total bilirubin less than 3.0 mg/dl.
- More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients’ toxicities must have recovered to a clinically manageable level (except for toxicities such as alopecia or vitiligo). (Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less).
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
- Any form of primary immunodeficiency (such as severe combined immunodeficiency disease).
- Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
- Active systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses.
- History of clinically significant major organ autoimmune disease.
- Concurrent systemic steroid therapy.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- History of active coronary or ischemic symptoms.
- Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%; note: testing is required in patients with: * Age >= 65 years’ old * Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain.
- Documented forced expiratory volume in one second (FEV1) less than or equal to 60% predicted tested in patients with: * A prolonged history of cigarette smoking (20 pack [pk]/year of smoking within the past 2 years). * Symptoms of respiratory dysfunction.
- Patients who are receiving any other investigational agents.
Locations & Contacts
Contact: Udai S. Kammula
Trial Objectives and Outline
I. To evaluate the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous tumor infiltrating lymphocyte (TIL) and high-dose aldesleukin in patients with locally advanced, recurrent, or metastatic biliary tract cancer using the objective response rate (ORR).
I. To further evaluate the efficacy of this therapy using complete response (CR) rate, duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
II. To characterize the safety profile of this therapy in patients with locally advanced, recurrent, or metastatic biliary tract cancer.
PREPARATIVE REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -7 to -6 and fludarabine IV over 30 minutes on days -5 to -1.
INFUSION: Patients undergo adoptive transfer of autologous TILs IV over 20-30 minutes on day 0. Within 24 hours, patients receive aldesleukin IV over 15 minutes every 8 hours for up to 6 doses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at 6 and 12 weeks, every 3 months for 9 months, and every 6 months for 1 year.
Trial Phase & Type
University of Pittsburgh Cancer Institute (UPCI)
Udai S. Kammula
Secondary IDs NCI-2019-02785
Clinicaltrials.gov ID NCT03801083