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RecruitingPhase 2

Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Cancer

A Phase II Study Using Short-Term Cultured, Autologous Tumor-Infiltrating Lymphocytes Following a Lymphodepleting Regimen in Metastatic Cancers Plus the Administration of Pembrolizumab

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years to 72 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Mentioned in the study description

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Time periods mentioned: 4 weeks, 2 days
  • Procedures mentioned: X-rays, Physical exams, Infusions

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Design: Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed."
  • "They will stay in the hospital for about 4 weeks for the treatment."
  • "Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking."
  • "Follow up visits will take up to 2 days."
  • "All patients will receive a non-myeloablative, lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the infusion of autologous TIL and high-dose aldesleukin."
  • "Patients enrolled on Arm 4 will receive pembrolizumab within four weeks after meeting progressive disease by RECIST criteria, continuing for up to 8 doses every 3 weeks. * Clinical and immunologic response will be evaluated about 6 weeks after cell infusion and periodically thereafter. * Twenty-one patients will initially be enrolled in each group to assess toxicity and tumor responses."
Compensation
Mentioned in the study description
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests whether selected white blood cells taken from a person's tumor can shrink cancer and be used safely. The cells are grown in a lab and given back with chemotherapy and a drug called aldesleukin. It is for adults ages 18–72 with certain cancers that have spread and have not responded to standard treatment.

Background: The NCI Surgery Branch has developed an experimental therapy that involves taking white blood cells 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, or TIL and we have given this type of treatment to over 200 patients with melanoma. Researchers want to know if TIL shrink s tumors in people with digestive tract, urothelial, breast, or ovarian/endometrial cancers. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells. Objective: The purpose of this study is to see if these specifically selected tumor fighting cells can cause digestive tract, urothelial, breast, or ovarian/endometrial tumors to shrink and to see if this treatment is safe. Eligibility: \- Adults age 18-72 with upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian/endometrial cancer, or glioblastoma refractory to standard chemotherapy. Design: Work up stage: Patients will be seen as an outpatient at the NIH clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed. Surgery: If the patients meet all of the requirements for the study they will undergo surgery to remove a tumor that can be used to grow the TIL product. Leukapheresis: Patients may undergo leukapheresis to obtain additional white blood cells. (Leukapheresis is a common procedure, which removes only the white blood cells from the patient.) Treatment: Once their cells have grown, the patients will be admitted to the hospital for the conditioning chemotherapy, the TIL cells and aldesleukin. They will stay in the hospital for about 4 weeks for the treatment. Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be 18–72 years old and able to do daily activities with little or no help.
  • Have cancer that has spread in the digestive tract, liver or bile ducts, urinary or reproductive organs, breast, ovaries, uterus lining, or hormone-making organs. The NCI lab must confirm the diagnosis.
  • Have cancer that can be measured and at least one tumor that can be removed with low risk to grow the treatment cells.
  • Standard drug treatment must have failed, and prior whole-body treatment must be finished. Some cancer types require specific past treatments.
  • Brain tumors from cancer spread may be allowed: up to 3 tumors smaller than 1 cm with no symptoms, or tumors removed by surgery. Tumors treated with focused radiation must be stable for one month.
  • Meet blood count, liver, and kidney test limits. HIV and hepatitis B tests must be negative. A positive hepatitis C antibody test requires a negative test for the virus itself.
  • If pregnancy is possible, have a negative pregnancy test and use birth control through 12 months after the last chemotherapy dose. People who can father children must use birth control through 4 months after treatment.
  • Understand and sign consent, name someone to make decisions if needed, and join study 03-C-0277.

Who can't join

  • Are pregnant or breastfeeding, take whole-body steroid treatment, or receive another experimental drug.
  • Have an active infection needing treatment, an infection linked to weak immune defenses, a blood-clotting disorder, or another serious active or poorly controlled illness.
  • Have an advanced main tumor at risk of causing blockage, a hole in an organ, or bleeding that requires blood transfusions.
  • Have an immune system deficiency, such as AIDS, or a history of disease where the immune system attacks a major organ.
  • Had severe immune-related harm to a major organ from anti-PD-1 or anti-PD-L1 cancer treatment.
  • Had a severe immediate allergic reaction to cyclophosphamide, fludarabine, or aldesleukin.
  • Had a procedure to restore blood flow to the heart or symptoms of low blood flow to the heart. Certain patients also cannot join if heart pumping strength is 45% or less or a breathing test result is 50% or less.
  • Have liver cell cancer with liver problems rated Child-Pugh class B or C, which means moderate or severe liver damage.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

* INCLUSION CRITERIA: * Measurable (per RECIST v1.0 criteria), metastatic cancer of one of the following types: upper or lower gastrointestinal, hepatobiliary, genitourinary, breast, ovarian/endometrial, or endocrine tumors including neuroendocrine tumors. Patients must have at least one lesion that is resectable for TIL generation with minimal morbidity, preferentially using minimal invasive laparoscopic or thoracoscopic surgery for removal of superficial tumor deposit. * Confirmation of diagnosis of metastatic cancer by the NCI Laboratory of Pathology. * Refractory to approved standard systemic therapy. Specifically: * Patients with metastatic colorectal cancer must have received oxaliplatin or irinotecan. * Patients with hepatocellular carcinoma must have received sorafenib (Nexavar(R)), since level 1 data support a survival benefit with this agent. * Patients with breast and ovarian cancer must be refractory to both first- and second-line treatments and must have received at least one second-line chemotherapy regimen. * Patients with 3 or fewer brain metastases that are \< 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible. * Age greater than or equal to 18 years and less than or equal to 72 years. * Clinical performance status of ECOG 0 or 1. * Patients of both sexes must be willing to practice birth control from the time of enrollment on this study and 12 months after the last dose of combined chemotherapy for individuals of child-bearing potential (IOCBP) and for four months after treatment for individuals that can father children. * IOCBP must have a negative pregnancy test be a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus. Serology * Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus may 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 the patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. Hematology * ANC \> 1000/mm\^3 without the support of filgrastim * WBC greater than or equal to 2500/mm\^3 * Platelet count greater than or equal to 80,000/mm\^3 * Hemoglobin \> 8.0 g/dL. Subjects may be transfused to reach this cut-off. Chemistry * Serum ALT/AST less than or equal to 5.0 x ULN * Serum creatinine less than or equal to 1.5 x ULN * Total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert s Syndrome, who must have a total bilirubin \< 3.0 mg/dL. * Patients must have completed any prior systemic therapy at the time of enrollment. Note: Patients may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to less than or equal to grade 1. * Ability of subject to understand and the willingness to sign a written informed consent document. * Willing to sign a durable power of attorney. * Subjects must be co-enrolled on protocol 03-C-0277. EXCLUSION CRITERIA: * Participants who are pregnant or nursing because of the potentially dangerous effects of the treatment on the fetus or infant. * Concurrent systemic steroid therapy. * Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses. * Advanced primary with impeding occlusion, perforation or bleeding, dependent on transfusion. * Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS). * History of major organ autoimmune disease. * Grade 3 or 4 major organ irAEs clinically attributed to anti-PD-1/PD-L1 therapy. * Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immunecompetence may be less responsive to the experimental treatment and more susceptible to its toxicities.) * History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin. * History of coronary revascularization or ischemic symptoms. * For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%. * Documented Child-Pugh score of B or C for hepatocellular carcinoma patients with known underlying liver dysfunction. * For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50%. * Patients who are receiving any other investigational agents.

Study sites (1)

MD