Cell Therapy (Tumor Infiltrating Lymphocytes) for the Treatment of Locally Advanced, Metastatic, or Recurrent Solid Cancers

Status: Active

Description

This phase II trial studies how well cell therapy (with tumor infiltrating lymphocytes) works for the treatment of solid cancer that has spread to nearby tissue or lymph nodes (locally advanced), has spread to other parts of the body (metastatic), or has come back (recurrent). This trial involves taking cells called lymphocytes (a type of white blood cell) from patients' tumors, growing them in the laboratory in large numbers, and then giving the cells back to the patient. These cells are called tumor infiltrating lymphocytes and the therapy is called cell therapy. Giving chemotherapy drugs before the cells may temporarily suppress the immune system to improve the chances that the tumor fighting cells will be able to survive in the body. Giving aldesleukin after the cell administration may help the tumor fighting cells stay alive longer. Giving tumor fighting cells (tumor infiltrating lymphocytes) followed by aldesleukin may cause the cancer to shrink.

Eligibility Criteria

Inclusion Criteria

  • Measurable locally advanced, recurrent, or metastatic cancer associated with one of the following cancer types: 1.) gastric/esophagogastric, 2.) colorectal, 3.) pancreatic, 4.) sarcoma, 5.) mesothelioma, 6.) neuroendocrine, 7.) squamous cell cancer, 8.) Merkel cell, 9.) mismatch repair deficient and/or microsatellite unstable cancers, and 10.) patients who have exhausted conventional systemic therapy options
  • Patients with locally advanced disease should be unresectable by conventional surgical approaches
  • Patients with distant metastatic spread must have previously received approved first-line systemic therapies 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 * Seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by real time-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 cell (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)

Exclusion Criteria

  • 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)
  • Clinically significant coagulation disorder
  • Active major medical illnesses deemed clinically significant by the treating physician
  • History of clinically significant major organ autoimmune disease * Patients with a history of hypothyroidism are eligible
  • 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 1 second (FEV1) less than or equal to 60% predicted tested in patients with: * A prolonged history of cigarette smoking (20 packs [pk]/year of smoking within the past 2 years) * Symptoms of respiratory dysfunction
  • Patients who are receiving any other investigational agents

Locations & Contacts

Pennsylvania

Pittsburgh
University of Pittsburgh Cancer Institute (UPCI)
Status: Active
Contact: Udai S. Kammula
Phone: 412-623-7712
Email: kammulaus@upmc.edu

Trial Objectives and Outline

PRIMARY OBJECTIVE:

I. To evaluate the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous tumor infiltrating lymphocytes (TIL) and high-dose aldesleukin in patients with locally advanced, recurrent, or metastatic cancer associated with one of the following cancer types: gastric/esophagogastric, colorectal, pancreatic, sarcoma, mesothelioma, neuroendocrine, squamous cell cancer, Merkel cell, mismatch repair deficient and/or microsatellite unstable cancers, and patients who have exhausted conventional systemic therapy options by using the objective response rate (ORR).

SECONDARY OBJECTIVES:

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 cancer associated with one of the following cancer types: gastric/esophagogastric, colorectal, pancreatic, sarcoma, mesothelioma, neuroendocrine, squamous cell cancer, Merkel cell, mismatch repair deficient and/or microsatellite unstable cancers, and patients who have exhausted conventional systemic therapy options.

OUTLINE:

Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -7 to -6 and fludarabine IV over 30 minutes on days -5 to -1. Patients then receive TIL IV over 20-30 minutes on day 0 and aldesleukin IV over 15 minutes on days 0-5 in the absence of disease progression or unacceptable toxicity. Beginning on day 1 or 2, patients may also receive filgrastim subcutaneously (SC) daily until neutrophil count > 1.0 x 10^9/L for 3 days or > 5.0 x 10^9/L.

After completion of study treatment, patients are followed up at 6 and 12 weeks, every 3 months the first year, and then every 6 months for the second year.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
University of Pittsburgh Cancer Institute (UPCI)

Principal Investigator
Udai S. Kammula

Trial IDs

Primary ID HCC 19-004
Secondary IDs NCI-2019-06773
Clinicaltrials.gov ID NCT03935893