NCT01369888

Brief Summary

Background: \- Researchers have developed an experimental cancer treatment called cell therapy. White blood cells called lymphocytes are taken from a tumor, grown in large numbers in the lab, and then given back to the patient. Interleukin-15, given to the patient after the cells (now called Young tumor-infiltrating lymphocytes of Young TIL cells) are replaced, helps the cells to grow and boosts the immune system. This process changes your normal cells into cells that are able to recognize your tumor has been studied in the lab. These cells can destroy tumor cells in the test tube, but scientists want to see if they work inside the body. Objectives:

  • To test the effectiveness of lymphocytes drawn from tumor cells combined with interleukin-15 in treating metastatic melanoma. Eligibility:
  • Patients must be 18 - 66 years of age and have a diagnosis of metastatic melanoma.
  • They will have heart and lung function tests, lab tests, and imaging procedures.
  • Patients may not have conditions such as active systemic infections, blood clotting disorders, or other active major medical illnesses.
  • Patients may not be pregnant or nursing.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started May 2011

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

May 1, 2011

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

June 8, 2011

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 9, 2011

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2014

Completed
9 months until next milestone

Results Posted

Study results publicly available

January 27, 2015

Completed
Last Updated

January 27, 2015

Status Verified

January 1, 2015

Enrollment Period

3 years

First QC Date

June 8, 2011

Results QC Date

January 15, 2015

Last Update Submit

January 26, 2015

Conditions

Keywords

ImmunotherapyCell TherapyIL-15 CytokineMelanomaMetastatic MelanomaSkin Cancer

Outcome Measures

Primary Outcomes (2)

  • Phase 1: Maximum Tolerated Dose (MTD) of Intravenous Recombinant IL-15 as a Daily Intravenous Bolus for 10 Consecutive Days in Patients With Metastatic Melanoma Who Have Received a Lymphodepleting Chemotherapy and ACT TIL.

    Intravenous recombinant IL-15 as a daily intravenous bolus for 10 consecutive days in patients with metastatic melanoma who have received a lymphodepleting chemotherapy and ACT TIL with dose escalation (i.e., dose level 1: 0.25 mcg, dose level 2: 0.50 mcg, dose level 3: 1 mcg, and dose level 4: 2 mcg) to further characterize the safety of the MTD prior to starting the phase 2 portion.

    2 years

  • Number of Participants With Adverse Events

    Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.

    8 months, 9 days

Study Arms (4)

IL-15 following Young TIL (0.25 mcg)

EXPERIMENTAL

0.25 mcg/kg/day x 10

Drug: CyclophosphamideDrug: FludarabineBiological: Tumor Infiltrating LymphocytesDrug: IL-15

IL-15 following Young TIL (0.50 mcg)

EXPERIMENTAL

0.50 mcg/kg/day x 10

Drug: CyclophosphamideDrug: FludarabineBiological: Tumor Infiltrating LymphocytesDrug: IL-15

IL-15 Following Young TIL (1 mcg)

EXPERIMENTAL

1 mcg/kg/day x 10

Drug: CyclophosphamideDrug: FludarabineBiological: Tumor Infiltrating LymphocytesDrug: IL-15

IL-15 Following Young TIL (2 mcg)

EXPERIMENTAL

2 mcg/kg/day x 10

Drug: CyclophosphamideDrug: FludarabineBiological: Tumor Infiltrating LymphocytesDrug: IL-15

Interventions

60 mg/m\^2, intravenous (IV) (in the vein) x 2 days

Also known as: Cytoxan
IL-15 Following Young TIL (1 mcg)IL-15 Following Young TIL (2 mcg)IL-15 following Young TIL (0.25 mcg)IL-15 following Young TIL (0.50 mcg)

25 mg/m\^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days (days -5 to -1)

Also known as: Fludara
IL-15 Following Young TIL (1 mcg)IL-15 Following Young TIL (2 mcg)IL-15 following Young TIL (0.25 mcg)IL-15 following Young TIL (0.50 mcg)

IV over 30 minutes on day 0

Also known as: TIL
IL-15 Following Young TIL (1 mcg)IL-15 Following Young TIL (2 mcg)IL-15 following Young TIL (0.25 mcg)IL-15 following Young TIL (0.50 mcg)
IL-15DRUG

IV over 30 minutes, daily for 10 days, starting 3-4 hours after the TIL infusion. (day 0 to day 9). Doses will be increased every 3-6 patients.

Also known as: Interleukin 15
IL-15 Following Young TIL (1 mcg)IL-15 Following Young TIL (2 mcg)IL-15 following Young TIL (0.25 mcg)IL-15 following Young TIL (0.50 mcg)

Eligibility Criteria

Age18 Years - 66 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Measurable metastatic melanoma with available autologous tumor infiltrating lymphocyte (TIL).
  • Patients with 3 or less brain metastases are eligible. Note: If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been treated and stable for 3 months for the patient to be eligible.
  • Greater than or equal to 18 years of age and less than or equal to age 66.
  • Able to understand and sign the Informed Consent Document
  • 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 preparative regimen.
  • 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 ribonucleic acid (HCV RNA) negative.
  • Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
  • Hematology:
  • Absolute neutrophil count greater than 1000/mm\^3 without the support of filgrastim.
  • White blood cell (WBC) (\> 3000/mm\^3).
  • Platelet count greater than 100,000/mm\^3.
  • +9 more criteria

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 major medical illnesses of the cardiovascular, respiratory or immune system, 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.
  • Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45%.
  • In patients \> 60 years old, documented LVEF of less than or equal to 45%.
  • Documented LVEF of less than or equal to 45% tested 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 or.
  • age greater than or equal to 60 years old.
  • Documented forced expiratory volume 1 (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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

    PMID: 17237035BACKGROUND
  • Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999 Jul;17(7):2105-16. doi: 10.1200/JCO.1999.17.7.2105.

    PMID: 10561265BACKGROUND
  • Gogas HJ, Kirkwood JM, Sondak VK. Chemotherapy for metastatic melanoma: time for a change? Cancer. 2007 Feb 1;109(3):455-64. doi: 10.1002/cncr.22427.

    PMID: 17200963BACKGROUND

MeSH Terms

Conditions

MelanomaSkin Neoplasms

Interventions

Cyclophosphamidefludarabinefludarabine phosphateInterleukin-15

Condition Hierarchy (Ancestors)

Neuroendocrine TumorsNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Nerve TissueNevi and MelanomasNeoplasms by SiteSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsInterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological Factors

Results Point of Contact

Title
Dr. Steven Rosenberg
Organization
National Cancer Institute

Study Officials

  • Steven A 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 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal investigator

Study Record Dates

First Submitted

June 8, 2011

First Posted

June 9, 2011

Study Start

May 1, 2011

Primary Completion

May 1, 2014

Study Completion

May 1, 2014

Last Updated

January 27, 2015

Results First Posted

January 27, 2015

Record last verified: 2015-01

Locations