Uveal NeoplasmsPhase 2NCT03467516
Adoptive Transfer of Tumor Infiltrating Lymphocytes for Metastatic Uveal Melanoma
A Phase 2 study testing Tumor Infiltrating Lymphocytes (TIL) in people with Uveal Neoplasms and Melanoma, Uveal, run by Udai Kammula at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Uveal Neoplasms, Melanoma, Uveal
- What is being tested?
- Tumor Infiltrating Lymphocytes (TIL)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 14 May 2018to 31 Dec 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 22Show fewer
- 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)
Who cannot join
- 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.
Show all 15Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
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
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.
Read the detailed description
STUDY DESIGN
The Phase 2 study will be conducted in conjunction with companion protocol (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) as described below:
Cell Preparation:
Patients with evaluable metastatic uveal melanoma who have lesions that can be resected with minimum morbidity will undergo resection of tumor. TIL will be obtained while enrolled on the companion protocol (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies). Separate tumor procurements may be performed under a protocol to obtain TIL if initial tumor procurements could not successfully generate TIL. The TIL will be grown and expanded for this trial according to standard operating procedures submitted in the IND. The TIL will be assessed for potency by interferon-gamma release.
Treatment Phase:
Once cells exceed the potency requirement and are projected to exceed the minimum number specified in the COA, the patient will be registered on this study and receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of up to 2x10^11 lymphocytes (minimum of 1x10^9 cells) and administration of high-dose intravenous aldesleukin. It is anticipated that TIL that meet the COA will not be achievable in approximately 20% of patients who undergo resection. These patients may undergo a second resection to grow TIL, if another suitable lesion exists. Approximately 6 weeks (+/- 2 weeks) after TIL administration, patients will undergo a complete tumor evaluation and evaluation of toxicity and immunologic parameters. Patients will receive one course of treatment. The start date of the course will be the start date of the chemotherapy; the end date will be the day of the first post-treatment evaluation. Patients may undergo a second treatment. Patients will receive no other experimental agents while on this protocol.
- Conditions
- Uveal Neoplasms, Melanoma, Uveal
- Being tested
- Tumor Infiltrating Lymphocytes (TIL)
- Keywords
- Metastatic Uveal Melanoma, Uveal Diseases, Melanoma
- Medical subject headings
- Uveal Neoplasms, Uveal Melanoma, Uveal Diseases, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor Infiltrating Lymphocytes (TIL)Biological
TIL infusion intravenously through a central vein catheter over 20-30 minutes. Folowed by Aldesleukin, administered at a dose of 600,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period approximately every 8 hours beginning within 24 hours of TIL infusion and continuing for up to a maximum of 6 doses.
| Study group | Role | What they receive |
|---|---|---|
| Tumor Infiltrating Lymphocytes (TIL) | Experimental | Patients with uveal melanoma will receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide followed by infusion of up to 2x10^11 TIL infused intravenously through a central vein catheter and Aldesleukin, administered at a dose of 600,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period approximately every 8 hours beginning within 24 hours of TIL infusion and continuing for up to a maximum of 6 doses. Receives: Biological: Tumor Infiltrating Lymphocytes (TIL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
The proportion of patients with response per RECIST for a (minimum) time period.
Equation: #patients with CR + #patients with PR / #patients with CR + #patients with PR + #patients with SD + #patients with PD
Measured: Post TIL infusion, up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)
Secondary outcomes (5)
Complete Response Rate (CRR)
The proportion of patients with complete response per RECIST for a (minimum) time period.
Equation: #patients with CR / #patients with CR + #patients with PR + #patients with SD + #patients with PD
Measured: : Post TIL infusion up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)
Duration of Response (DOR)
Time between the initial response to treatment per RECIST and subsequent disease progression (Median 'time to progression' (months) among patients achieving CR or PR).
Measured: Up to 24 months
Disease Control Rate (DCR)
The proportion of patients with response or stable disease per RECIST for a (minimum) time period. Equation: # patients with CR + # patients with PR + # patients with SD / # patients with CR + # patients with PR + # patients with SD + # patients with PD
Measured: Post TIL infusion up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)
Progression Free Survival (PFS)
The length of time after TIL infusion that a patient lives with the disease but it does not get worse.
Measured: Post TIL infusion up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)
Overall Survival (OS)
The length of time from the start of treatment that patients are still alive.
Measured: Post TIL infusion up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2018
- Study start14 May 2018
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Uveal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The Phase 2 study will follow the Simon's optimal two-stage design. Fifteen patients will be included in the first stage; if there are 1 or fewer patients responding to therapy the trial will be terminated. If at least 2 responses are observed, expansion into Stage 2 to a total of 47 patients will occur. If at least 6 patients respond to therapy, the study therapy would be considered to have met its primary study goal.
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Udai Kammula
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Udai Kammula, University of Pittsburgh
- Investigators
- Udai S Kammula, MD, Principal investigator, UPMC Hillman Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03467516
- Sponsor's protocol ID
- HCC 17-219
- Status last verified
- May 2026
- First submitted
- 9 Mar 2018
- Last updated
- 1 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03467516
- Acronym / sponsor ID
- HCC 17-219
- Conditions
- Uveal Neoplasms, Melanoma, Uveal
- Keywords
- Metastatic Uveal Melanoma, Uveal Diseases, Melanoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Udai KammulaUniversity, hospital or other
- Study start
- 14 May 2018 (actual)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 16 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
STUDY DESIGN
The Phase 2 study will be conducted in conjunction with companion protocol (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) as described below:
Cell Preparation:
Patients with evaluable metastatic uveal melanoma who have lesions that can be resected with minimum morbidity will undergo resection of tumor. TIL will be obtained while enrolled on the companion protocol (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies). Separate tumor procurements may be performed under a protocol to obtain TIL if initial tumor procurements could not successfully generate TIL. The TIL will be grown and expanded for this trial according to standard operating procedures submitted in the IND. The TIL will be assessed for potency by interferon-gamma release.
Treatment Phase:
Once cells exceed the potency requirement and are projected to exceed the minimum number specified in the COA, the patient will be registered on this study and receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of up to 2x10^11 lymphocytes (minimum of 1x10^9 cells) and administration of high-dose intravenous aldesleukin. It is anticipated that TIL that meet the COA will not be achievable in approximately 20% of patients who undergo resection. These patients may undergo a second resection to grow TIL, if another suitable lesion exists. Approximately 6 weeks (+/- 2 weeks) after TIL administration, patients will undergo a complete tumor evaluation and evaluation of toxicity and immunologic parameters. Patients will receive one course of treatment. The start date of the course will be the start date of the chemotherapy; the end date will be the day of the first post-treatment evaluation. Patients may undergo a second treatment. Patients will receive no other experimental agents while on this protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The Phase 2 study will follow the Simon's optimal two-stage design. Fifteen patients will be included in the first stage; if there are 1 or fewer patients responding to therapy the trial will be terminated. If at least 2 responses are observed, expansion into Stage 2 to a total of 47 patients will occur. If at least 6 patients respond to therapy, the study therapy would be considered to have met its primary study goal.
| Arm | Type | Receives |
|---|---|---|
| Tumor Infiltrating Lymphocytes (TIL) | Experimental | Biological: Tumor Infiltrating Lymphocytes (TIL)Patients with uveal melanoma will receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide followed by infusion of up to 2x10^11 TIL infused intravenously through a central vein catheter and Aldesleukin, administered at a dose of 600,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period approximately every 8 hours beginning within 24 hours of TIL infusion and continuing for up to a maximum of 6 doses. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- 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
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tumor Infiltrating Lymphocytes (TIL)TIL infusion intravenously through a central vein catheter over 20-30 minutes. Folowed by Aldesleukin, administered at a dose of 600,000 IU/kg (based on total body weight) as an intravenous bolus over a 15-minute period approximately every 8 hours beginning within 24 hours of TIL infusion and continuing for up to a maximum of 6 doses. | Biological | Tumor Infiltrating Lymphocytes (TIL) |
Primary outcome
Objective Response Rate (ORR)
Time frame: Post TIL infusion, up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)
The proportion of patients with response per RECIST for a (minimum) time period. Equation: #patients with CR + #patients with PR / #patients with CR + #patients with PR + #patients with SD + #patients with PD
5 secondary outcomes
Complete Response Rate (CRR)
Time frame: : Post TIL infusion up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)
Duration of Response (DOR)
Time frame: Up to 24 months
Disease Control Rate (DCR)
Time frame: Post TIL infusion up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)
Progression Free Survival (PFS)
Time frame: Post TIL infusion up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)
Overall Survival (OS)
Time frame: Post TIL infusion up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jun 2026.
- Individual participant dataSharing planned: No
Related trials for Uveal Neoplasms
RecruitingObservational study
High-precision Radiosurgery Followed by Minimally Invasive Surgical Approach in Patients With High-prominence Uveal Melanoma: Modern Radiation Techniques and Outcomes
Uveal Melanoma, High-risk Uveal Melanoma
RecruitingPhase 1/2
A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors
Hepatocellular Carcinoma (HCC), Metastatic Uveal Melanoma
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingPhase 2
HS-IT101 Injection Versus Chemotherapy in the Treatment of Advanced Melanoma（FASTIL-Mela02）
Melanoma (Excluding Uveal Melanoma)
Recruiting
Immune Response to Percutaneous Hepatic Perfusion With Melphalan for Ocular Melanoma Metastatic to the Liver
Uveal Melanoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Udai S Kammula, MD principal investigator
UPMC Hillman Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tumor Infiltrating Lymphocytes (TIL) in people with Uveal Neoplasms and Melanoma, Uveal, run by Udai Kammula at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective Response Rate (ORR) (time frame: Post TIL infusion, up to 24 months (measurements taken at 6 weeks, 12 weeks, 6 months, 9 months, 12 months, 18 months 24 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jun 2026.