RECRUITING

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Metastatic Uveal Melanoma

Conditions

Uveal Neoplasms Melanoma, Uveal Metastatic Uveal Melanoma Uveal Diseases Melanoma

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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

This is a Phase 2 study in which the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous TIL and high-dose aldesleukin in patients with metastatic uveal melanoma will be evaluated. Metastatic uveal melanoma (UM) carries a poor prognosis with estimated survival of 4-6 months. There are no known effective systemic therapies. Metastatic UM is classified as an "orphan" disease and there are currently few clinical trial options for these patients. Thus, novel systemic approaches are desperately needed. A recent pilot study has found that administration of autologous tumor infiltrating lymphocytes (TIL) generated from resected metastases can induce objective tumor response and durable complete response in metastatic uveal melanoma patients. These encouraging results require confirmation to determine if this immunotherapy is of future benefit in treating this disease.

Official Title

A Phase 2 Study to Evaluate the Efficacy and Safety of Adoptive Transfer of Autologous Tumor Infiltrating Lymphocytes in Patients With Metastatic Uveal Melanoma

Quick Facts

Study Start:2018-05-14

Study Completion:2027-12-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03467516

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 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Measurable metastatic uveal melanoma. * 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. * Greater than or equal to 18 years of age and less than or equal to age 75 * Able to understand and sign the Informed Consent Document * Clinical performance status of ECOG 0 or 1 * Life expectancy of greater than three months * 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 receiving the treatment. * 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 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 RT-PCR and be HCV 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. * Hematology * Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim * WBC ≥ 3000/mm3 * Platelet count ≥ 100,000/mm3 * Hemoglobin \> 8.0 g/dl * Chemistry * Serum ALT/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 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 FEV1 less than or equal to 60% predicted tested in patients with: * A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years). * Symptoms of respiratory dysfunction * Patients who are receiving any other investigational agents.

Inclusion Criteria

Exclusion Criteria

* Measurable metastatic uveal melanoma.
* 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.
* Greater than or equal to 18 years of age and less than or equal to age 75
* Able to understand and sign the Informed Consent Document
* Clinical performance status of ECOG 0 or 1
* Life expectancy of greater than three months
* 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 receiving the treatment.
* 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 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 RT-PCR and be HCV 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.
* Hematology
* Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim
* WBC ≥ 3000/mm3
* Platelet count ≥ 100,000/mm3
* Hemoglobin \> 8.0 g/dl
* Chemistry
* Serum ALT/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 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 FEV1 less than or equal to 60% predicted tested in patients with:
* A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).
* Symptoms of respiratory dysfunction
* Patients who are receiving any other investigational agents.

Contacts and Locations

Study Contact

Josh Tobin, RN

CONTACT

412-864-7754

tobinja@upmc.edu

Allyson Welsch, RN

CONTACT

412-623-6763

welscha2@upmc.edu

Principal Investigator

Udai S Kammula, MD

PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Study Locations (Sites)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

United States

Collaborators and Investigators

Sponsor: Udai Kammula

Udai S Kammula, MD, PRINCIPAL_INVESTIGATOR, UPMC Hillman Cancer Center

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 Date2018-05-14

Study Completion Date2027-12-31

Study Record Updates

Study Start Date2018-05-14

Study Completion Date2027-12-31

Terms related to this study

Keywords Provided by Researchers

Metastatic Uveal Melanoma
Uveal Diseases
Melanoma

Additional Relevant MeSH Terms

Uveal Neoplasms
Melanoma, Uveal