Modified Tumor Infiltrating Lymphocytes for Metastatic Melanoma

NCT01369875 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 11016311-C-0163
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Tumor infiltrating lymphocytes (TIL) are white blood cells that have been taken from tumor tissue. The cells are modified to help them kill tumor cells, then given back to the person with cancer. By giving these cells to patients, researchers hope to improve the current treatments available for patients with melanoma that has not responded to standard therapies. The TIL will be given after treatments that will suppress the immune system. This makes it easier for the TIL to attack the cancer cells. The TIL will also be given with aldesleukin (IL-2), which is designed to help keep the TIL cells alive in the body. Objectives: \- To study the safety and effectiveness of specially modified tumor infiltrating lymphocytes to treat melanoma that has not responded to other treatments. Eligibility: \- Individuals at least 18 years of age who have metastatic melanoma that has not responded to other treatments. Design:

• Participants will be screened with a physical exam and medical history. They will also have blood tests and imaging studies.
• A piece of tumor will be collected and white blood cells will be separated to make the TIL for the treatment.
• Participants will take drugs to suppress the immune system for 7 days before the start of treatment.
• Participants will receive the TIL in a single dose. Then they will receive IL-2 every 8 hours for up to 15 doses. Participants will remain in the hospital for up to 2 weeks after treatment. They will be monitored with frequent blood tests and other studies.
• After leaving the hospital, participants will have regular followup visits every 1 to 4 months for the first year. Then they will return for followup every 3 to 4 months, as directed by the study researchers.

Conditions

Metastatic Melanoma; Skin Cancer

Keywords

Immunotherapy; Cell Therapy; Metastatic Cancer; Melanoma; Metastatic Melanoma; Skin Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Clinical Tumor Regression.

  Clinical tumor regression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is a disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progression (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD.

  up to approximately 8 months

Secondary Outcomes (1)

• Number of Participants With Serious and Non-Serious Adverse Events

  Date treatment consent signed to date off study, up to approximately 8 months.

Study Arms (2)

Standard Young TIL

EXPERIMENTAL

Tumor Infiltrating Lymphocytes : intravenous (IV) over 30 minutes on day 0 Aldesleukin : 720,000 IU/kg IV over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.) Fludarabine : 25 mg/m2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days (days -5 to -1) Cyclophosphamide : 60 mg/kg/day X 2 days IV over 1 hour on days -7 and -6

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Aldesleukin; Biological: Tumor Infiltrating Lymphocytes

ECCE Young TIL

EXPERIMENTAL

Tumor Infiltrating Lymphocytes : IV over 30 minutes on day 0 Aldesleukin : 720,000 IU/kg IV over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.) Fludarabine : 25 mg/m2/day IVPB daily over 30 minutes for 5 days (days -5 to -1) Cyclophosphamide : 60 mg/kg/day X 2 days IV over 1 hour on days -7 and -6

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Aldesleukin; Biological: Tumor Infiltrating Lymphocytes

Interventions

Cyclophosphamide DRUG

60 mg/kg/day X 2 days intravenous (IV) over 1 hour on days -7 and -6

Also known as: Cytoxan

ECCE Young TIL; Standard Young TIL

Fludarabine DRUG

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

Also known as: Fludara

ECCE Young TIL; Standard Young TIL

Aldesleukin BIOLOGICAL

720,000 IU/kg intravenous (IV) over 15 min every 8 hours (+/- 1hr) beginning within 24 hours of cell infusion and continuing for up to 5 days (max. 15 doses.)

Also known as: IL-2

ECCE Young TIL; Standard Young TIL

Tumor Infiltrating Lymphocytes BIOLOGICAL

Intravenous (IV) over 30 minutes on day 0

ECCE Young TIL; Standard Young TIL

Eligibility Criteria

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

You may qualify if:

• Measurable metastatic melanoma with at least one lesion that is resectable for tumor infiltrating lymphocytes (TIL) generation.
• 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.
• Willing to sign a durable power of attorney
• 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 engineered cells with costimulation enhancement (ECCE) TIL 14 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).

You may not qualify if:

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
• Systemic steroid therapy required.
• 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 ECCE TIL 15 have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• History of coronary revascularization or ischemic symptoms
• Any patient known to have an left ventricular ejection fraction (LVEF) 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
• 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
• Symptoms of respiratory dysfunction

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 (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: 17237035 BACKGROUND

• 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: 10561265 BACKGROUND

• 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: 17200963 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Melanoma; Skin Neoplasms; Neoplasm Metastasis

Interventions

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

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Steven Rosenberg
• Organization: National Cancer Institute, National Institutes of Health

sar@mail.nih.gov

301-496-4164

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• 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: June 17, 2011
• Primary Completion: February 13, 2012
• Study Completion: February 14, 2012
• Last Updated: December 10, 2019
• Results First Posted: March 21, 2013

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)