RECRUITING

A Phase 2 Trial for Metastatic Melanoma Using Adoptive Cell Therapy With Tumor Infiltrating Lymphocytes Plus IL-2 Either Alone or Following the Administration of Pembrolizumab

Conditions

Melanoma Skin Cancer Immunotherapy Cell Therapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Background: Cell therapy is an experimental cancer therapy. It takes young tumor infiltrating lymphocytes (Young TIL) cells from a person s tumors and grows them in a lab. Then they are returned to the person. Researchers think adding the drug pembrolizumab might make the therapy more effective. Objective: To test if adding pembrolizumab to cell therapy is safe and effective to shrink melanoma tumors. Eligibility: People ages 18-72 years with metastatic melanoma OF THE SKIN Design: Participants will be screened with: Physical exam CT, MRI, or PET scans X-rays Heart and lung function tests if indicated Blood and urine tests Before treatment, participants will have: A piece of tumor taken from a biopsy or during surgery in order to grow TIL cells Leukapheresis: Blood flows through a needle in one arm and into a machine that removes white blood cells. The rest of the blood returns through a needle in the other arm. An IV catheter placed in the chest for getting TIL cells, aldesleukin, and pembrolizumab (if assigned) Participants will stay in the hospital for treatment. This includes: Daily chemotherapy for 1 week For some participants, pembrolizumab infusion 1 day after chemotherapy TIL cell infusion 2-4 days after chemotherapy, then aldesleukin infusion every 8 hours for up to 12 doses Filgrastim injections to help restore your blood counts Recovery for 1-3 weeks After treatment, participants will: Take an antibiotic and an antiviral for at least 6 months, as applicable If assigned, have pembrolizumab treatment every 3 weeks for 3 more doses. They may have another round. Have 2-day follow-up visits every 1-3 months for 1 year and then every 6 months

Official Title

A Phase II Trial for Metastatic Melanoma Using Adoptive Cell Therapy With Tumor-Infiltrating Lymphocytes Plus IL-2 Either Alone or Following the Administration of Pembrolizumab

Quick Facts

Study Start:2015-12-04

Study Completion:2029-06-16

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT02621021

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 72 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation. 2. Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of NCI. 3. Patients must have received at least one prior therapy for metastatic melanoma. 4. 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. 5. Greater than or equal to 18 years of age and less than or equal to 72 years of age. 6. All participants must sign a written informed consent. 7. All participants must be willing to sign a durable power of attorney 8. Clinical performance status of ECOG 0 or 1. 9. Patients of both sexes must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment. 10. Serology: * Seronegative for 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 are 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 RT-PCR and be HCV RNA negative. 11. Individuals of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus. 12. Individuals of child-bearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \[IUD, abstinence, surgical sterilization starting at the time of study entry, for the duration of study therapy, and 12 months after the last dose of combined chemotherapy 13. Nursing participants must be willing to discontinue nursing from study treatment initiation through 4 months after the last dose of the study drug(s). 14. Hematology * Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim * WBC greater than or equal to 2500/mm3 * Platelet count greater than or equal to 800,000/mm3 * Hemoglobin \> 8.0 g/dl 15. Chemistry: * Serum ALT/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 1.5 mg/dl, except in patients with Gilbert s Syndrome who musthave a total bilirubin less than 3.0 mg/dl. 16. Patients must have completed any prior systemic therapy at the time of enrollment. 17. Patients must demonstrate progressive disease at the time of treatment. (Note: Patients who have received tyrosine kinase inhibitors (e.g. vemurafinib) may be treated if they present with stable disease at the time of treatment). 18. Patients must be co-enrolled in protocol 03-C-0277.	1. Individuals of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant. 2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). 3. 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). 4. Active systemic infections requiring anti-infective treatment, coagulation disorders or any other active major medical illnesses. 5. History of major organ autoimmune disease 6. Concurrent systemic steroid therapy. 7. History of severe immediate hypersensitivity reaction to any of the agents used in this study. 8. Grade 3 or 4 Major organ Immune-related Adverse Events (IRAEs) clinically attributed to anti PD-1/PD-L1 monotherapy. Previously screened participants that experience these IRAEs after resection for creation of TIL are excluded from Arms 2, but may be eligible for assignment to Arm3. NOTE: For the purposes of this protocol, thyroid is not considered a major organ. 9. History of coronary revascularization or ischemic symptoms. 10. For select patients with a clinical history prompting cardiac evaluation: last LVEF of less than or equal to 45% 11. For select patients with a clinical history promptin pulmonary evaluation: known FEV1 less than or equal to 50%. 12. Patients who are receiving any other investigational agents.

Inclusion Criteria

Exclusion Criteria

1. Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation.
2. Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of NCI.
3. Patients must have received at least one prior therapy for metastatic melanoma.
4. 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.
5. Greater than or equal to 18 years of age and less than or equal to 72 years of age.
6. All participants must sign a written informed consent.
7. All participants must be willing to sign a durable power of attorney
8. Clinical performance status of ECOG 0 or 1.
9. Patients of both sexes must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment.
10. Serology:
* Seronegative for 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 are 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 RT-PCR and be HCV RNA negative.
11. Individuals of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.
12. Individuals of child-bearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \[IUD, abstinence, surgical sterilization starting at the time of study entry, for the duration of study therapy, and 12 months after the last dose of combined chemotherapy
13. Nursing participants must be willing to discontinue nursing from study treatment initiation through 4 months after the last dose of the study drug(s).
14. Hematology
* Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim
* WBC greater than or equal to 2500/mm3
* Platelet count greater than or equal to 800,000/mm3
* Hemoglobin \> 8.0 g/dl
15. Chemistry:
* Serum ALT/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 1.5 mg/dl, except in patients with Gilbert s Syndrome who musthave a total bilirubin less than 3.0 mg/dl.
16. Patients must have completed any prior systemic therapy at the time of enrollment.
17. Patients must demonstrate progressive disease at the time of treatment. (Note: Patients who have received tyrosine kinase inhibitors (e.g. vemurafinib) may be treated if they present with stable disease at the time of treatment).
18. Patients must be co-enrolled in protocol 03-C-0277.

1. Individuals of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
3. 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).
4. Active systemic infections requiring anti-infective treatment, coagulation disorders or any other active major medical illnesses.
5. History of major organ autoimmune disease
6. Concurrent systemic steroid therapy.
7. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
8. Grade 3 or 4 Major organ Immune-related Adverse Events (IRAEs) clinically attributed to anti PD-1/PD-L1 monotherapy. Previously screened participants that experience these IRAEs after resection for creation of TIL are excluded from Arms 2, but may be eligible for assignment to Arm3. NOTE: For the purposes of this protocol, thyroid is not considered a major organ.
9. History of coronary revascularization or ischemic symptoms.
10. For select patients with a clinical history prompting cardiac evaluation: last LVEF of less than or equal to 45%
11. For select patients with a clinical history promptin pulmonary evaluation: known FEV1 less than or equal to 50%.
12. Patients who are receiving any other investigational agents.

Contacts and Locations

Study Contact

NCI/Surgery Branch Recruitment Center

CONTACT

(866) 820-4505

IRC@nih.gov

Principal Investigator

Stephanie L Goff, M.D.

PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Stephanie L Goff, M.D., PRINCIPAL_INVESTIGATOR, National Cancer Institute (NCI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2015-12-04

Study Completion Date2029-06-16

Study Record Updates

Study Start Date2015-12-04

Study Completion Date2029-06-16

Terms related to this study

Keywords Provided by Researchers

Melanoma
Skin Cancer
Immunotherapy
Cell Therapy

Additional Relevant MeSH Terms

Melanoma