Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Ocular Melanoma

Phase 2

Terminated

Conditions: Metastatic Ocular Melanoma
Metastatic Uveal Melanoma

Interventions: Drug: Aldesleukin
Drug: Cyclophosphamide
Drug: Fludarabine
Biological: Young Tumor Infiltrating Lymphocytes (TIL)

Registration Number: NCT01814046

Lead Sponsor: National Cancer Institute (NCI)

Brief 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 200 patients with melanoma. This study will use chemotherapy to prepare the immune system before this white blood cell treatment. After receiving the cells, the drug aldesleukin (IL-2) may be given to help the cells stay alive longer.

Objectives:

- To see if chemotherapy and white blood cell therapy is a safe and effective treatment for advanced ocular melanoma.

Eligibility:

- Individuals at least greater than or equal to 16 years to less than or equal to 75 years who have advanced ocular melanoma.

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 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.

Detailed Description: Background:

* Metastatic ocular melanoma (OM) carries a poor prognosis with estimated survival of 4-6 months. There are no known effective systemic therapies. Metastatic OM is classified as an orphan disease and there are currently few clinical trial options for these patients. Thus, novel systemic approaches are desperately needed.

* Administration of autologous tumor infiltrating lymphocytes (TIL) generated from resected metastatic cutaneous melanoma can induce objective long-term tumor responses.

* Minimally invasive, safe, and effective surgical approaches have been developed in the Surgery Branch to procure liver tumor tissue for TIL generation.

Objectives:

* To determine whether autologous Young TIL infused with or without the administration of high-dose aldesleukin may result in clinical tumor regression in patients with metastatic ocular melanoma receiving a non-myeloablative lymphoid depleting preparative regimen.

* To study immunologic correlates associated with Young TIL therapy for ocular melanoma.

* To determine the toxicity of this treatment regimen.

Eligibility:

* Patients with metastatic ocular melanoma who are greater than or equal to 16 years of age, and are physically able to tolerate non-myeloablative chemotherapy. Patients who can tolerate high-dose aldesleukin will receive it following cell infusion; those who cannot tolerate high-dose aldesleukin due to medical comorbidities or refuse high dose aldesleukin will receive cell infusion without aldesleukin.

* There is no requirement for prior systemic therapies, given the lack of known effective systemic treatments for metastatic OM.

Design:

* Patients will undergo biopsy or resection to obtain tumor for generation of autologous TIL cultures and autologous cancer cell lines.

* All patients will receive a non-myeloablative lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine.

* On day 0 patients will receive between 1x10\^9 to 2x10\^11 young TIL and then begin high dose aldesleukin (720,000 IU/kg intravenous (IV) every 8 hours for up to 15 doses) or no aldesleukin if they are not medically eligible to receive it.

* A complete evaluation of evaluable lesions will be conducted 4-6 weeks after the last dose of aldesleukin in the aldesleukin arm and 4-6 weeks after the cell administration in the no aldesleukin arm.

* Patients will be enrolled into two cohorts. The cohort receiving high-dose aldesleukin (cohort A) will be conducted using a small optimal two-stage Phase II design, initially 19 patients will be enrolled, and if 4 or more of the first 19 patients have a clinical response (partial response (PR) or complete response (CR), accrual will continue to 33 patients, targeting a 35% goal for objective response. For the cohort that will not receive aldesleukin (cohort B), the study will be conducted as a Minimax two-stage phase II trial. Initially 12 evaluable patients will be enrolled to this cohort, and if 1 or more the first 12 have a response, then accrual would continue until a total of 21 patients, targeting a 20% goal for objective response.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 24

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
cells + high dose aldesleukin	Young Tumor Infiltrating Lymphocytes (TIL)	Patients receiving cells + high dose aldesleukin
cells + high dose aldesleukin	Aldesleukin	Patients receiving cells + high dose aldesleukin
cells + high dose aldesleukin	Fludarabine	Patients receiving cells + high dose aldesleukin
cells and no high dose aldesleukin	Young Tumor Infiltrating Lymphocytes (TIL)	Patients receiving cells and no high dose aldesleukin
cells + high dose aldesleukin	Cyclophosphamide	Patients receiving cells + high dose aldesleukin
cells and no high dose aldesleukin	Cyclophosphamide	Patients receiving cells and no high dose aldesleukin
cells and no high dose aldesleukin	Fludarabine	Patients receiving cells and no high dose aldesleukin

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Ocular Melanoma Treated With Young Tumor Infiltrating Lymphocytes (TIL) With or Without High Dose Aldesleukin With an Objective Response Rate of (Complete Response (CR) + Partial Response (PR))	approximately 3 years	Objective response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

Secondary Outcome Measures

Name	Time	Method
Count of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0)	46 months and 12 days	Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.