Immunotherapy Using 41BB Selected Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma

• Status: Terminated
• Trial end date: 2016-07-21
• Target enrollment: 0
• Participant gender: All

Summary

Background:

The National Cancer Institute (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 100 patients. 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 melanoma tumors to shrink and to see if this treatment is safe.

Eligibility:

• Adults age 18-70 with metastatic melanoma who have a tumor that can be safely removed.

Design:

• Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (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 tumor infiltrating lymphocytes (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 take up to 2 days.

...

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate

Criteria

-INCLUSION CRITERIA:

1. Measurable metastatic melanoma with at least one lesion that is resectable for tumor infiltrating lymphocytes (TIL) generation. The lesion must be at least 1 cm in diameter that can be surgically removed with minimal morbidity (defined as any operation for which expected hospitalization2. Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of the National Cancer Institute (NCI).

3. 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.

4. Greater than or equal to 18 years of age and less than or equal to age 70.

5. Able to understand and sign the Informed Consent Document

6. Willing to sign a durable power of attorney

7. Clinical performance status of Easter Cooperative Oncology Group (ECOG) 0 or 1

8. Oxygen saturation of greater than or equal to 90% on room air

9. Life expectancy of greater than three months

10. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment.

11. 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 ribonucleic acid (HCV RNA) negative.

12. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.

13. Hematology

• Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim

• White blood cell (WBC) greater than or equal to 3000/mm^3

• Platelet count greater than or equal to 100,000/mm^3

• Hemoglobin > 8.0 g/dl

14. Chemistry:

• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than or equal to 2.5 times the upper limit of normal

• Serum creatinine less than or equal to 1.6 mg/dl

• Total bilirubin less than or equal to 2.0 mg/dl, except in patients with Gilberts Syndrome who must have a total bilirubin less than 3.0 mg/dl.

15. 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 grade 1 or less (except for toxicities such as alopecia or vitiligo). Patients must have progressing disease after prior treatment.

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 or as specified in the eligibility criteria in Section 2.1.1.

16. Six weeks must have elapsed from the time of any antibody therapy that could affect an anti cancer immune response, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibody therapy at the time the patient receives the preparative regimen to allow antibody levels to decline.

Note: Patients who have previously received ipilimumab and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

1. Prior treatment with an anti-4-1BB antibody.

2. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.

3. Active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).

5. 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).

6. Concurrent systemic steroid therapy.

7. History of severe immediate hypersensitivity reaction to any of the agents used in this study.

8. History of coronary revascularization or ischemic symptoms.

9. Documented left ventricular ejection fraction (LVEF) of less than or equal to 45%, testing is required in patients with:

• Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block

• Age greater than or equal to 60 years old