Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Ocular Melanoma

NCT01814046 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 13009313-C-0093
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Ocular Melanoma; Metastatic Uveal Melanoma

Keywords

Metastatic; Ocular Melanoma; Autologous Tumor-Infiltrating Lymphocytes; Uveal Melanoma; Adoptive Cell Therapy

Outcome Measures

Primary Outcomes (1)

• 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))

  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.

  approximately 3 years

Secondary Outcomes (1)

• 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

Other Outcomes (1)

• Count of Participants With Changes in Visual Symptoms

  6 weeks (+/- 2 weeks)

Study Arms (2)

cells + high dose aldesleukin

EXPERIMENTAL

Patients receiving cells + high dose aldesleukin

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

cells and no high dose aldesleukin

EXPERIMENTAL

Patients receiving cells and no high dose aldesleukin

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

Interventions

Aldesleukin DRUG

Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight) over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses) (only for cohort A).

Also known as: Interleukin-2

cells + high dose aldesleukin

Cyclophosphamide DRUG

Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 ml dextrose 5% water (D5W) with Mesna 15 mg/kg/day X 2 days over 1 hr.

Also known as: Cytoxan

cells + high dose aldesleukin; cells and no high dose aldesleukin

Fludarabine DRUG

Fludarabine 25 mg/m\^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.

Also known as: Fludara

cells + high dose aldesleukin; cells and no high dose aldesleukin

Young Tumor Infiltrating Lymphocytes (TIL) BIOLOGICAL

Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of young TIL and high dose aldesleukin (Cohort A) or no aldesleukin (Cohort B). On day 0,cells (1x10e9 to 2x10e11) will be infused intravenously on the Patient Care Unit over 20-30 minutes.

cells + high dose aldesleukin; cells and no high dose aldesleukin

Eligibility Criteria

• Age: 16 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable metastatic ocular melanoma.
• Confirmation of diagnosis of metastatic ocular melanoma by the Laboratory of Pathology of the National Cancer Institute (NCI).
• 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 16 years of age and less than or equal to age 75.
• Able to understand and sign the Informed Consent Document
• Willing to sign a durable power of attorney
• Clinical performance status of Eastern Cooperative Oncology Group (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 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 (HCV) ribonucleic acid (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/mm\^3 without the support of filgrastim

You may not qualify if:

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
• 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.
• 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).
• Concurrent systemic steroid therapy.
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• The following patients will be excluded from the high-dose aldesleukin arm (but may be eligible for cells alone arm):
• History of coronary revascularization or ischemic symptoms
• 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
• Clinically significant patient history which in the judgment of the Principal Investigator would compromise the patients ability to tolerate aldesleukin

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Woodman SE. Metastatic uveal melanoma: biology and emerging treatments. Cancer J. 2012 Mar-Apr;18(2):148-52. doi: 10.1097/PPO.0b013e31824bd256.

  PMID: 22453016 BACKGROUND

• Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR, Morton KE, Laurencot CM, Steinberg SM, White DE, Dudley ME. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011 Jul 1;17(13):4550-7. doi: 10.1158/1078-0432.CCR-11-0116. Epub 2011 Apr 15.

  PMID: 21498393 BACKGROUND

• Singh AD, Turell ME, Topham AK. Uveal melanoma: trends in incidence, treatment, and survival. Ophthalmology. 2011 Sep;118(9):1881-5. doi: 10.1016/j.ophtha.2011.01.040. Epub 2011 Jun 24.

  PMID: 21704381 BACKGROUND

• Chandran SS, Somerville RPT, Yang JC, Sherry RM, Klebanoff CA, Goff SL, Wunderlich JR, Danforth DN, Zlott D, Paria BC, Sabesan AC, Srivastava AK, Xi L, Pham TH, Raffeld M, White DE, Toomey MA, Rosenberg SA, Kammula US. Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study. Lancet Oncol. 2017 Jun;18(6):792-802. doi: 10.1016/S1470-2045(17)30251-6. Epub 2017 Apr 7.

  PMID: 28395880 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Uveal Melanoma; Neoplasm Metastasis

Interventions

aldesleukin; Interleukin-2; Cyclophosphamide; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Steven Rosenberg
• Organization: National Cancer Institute

steven-rosenberg@nih.gov

301-496-4164

Study Officials

• Steven Rosenberg, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 15, 2013
• First Posted: March 19, 2013
• Study Start: March 1, 2013
• Primary Completion: May 1, 2017
• Study Completion: May 31, 2017
• Last Updated: October 11, 2018
• Results First Posted: July 24, 2017

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)