Immunotherapy Using 41BB Selected Tumor Infiltrating Lymphocytes for Patients With Metastatic Melanoma

NCT02111863 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 14006214-C-0062
• Study Type: interventional
• Target: 6
• 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 100 patients. In this study, we are selecting a specific subset of white blood cells from the tumor that we think are the most effective in fighting tumors and will use only these cells in making the tumor fighting cells. Objective: The purpose of this study is to see if these specifically selected tumor fighting cells can cause melanoma tumors to shrink and to see if this treatment is safe. Eligibility: \- Adults age 18-70 with metastatic melanoma who have a tumor that can be safely removed. 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 tumor infiltrating lymphocytes (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

Melanoma; Skin Cancer

Keywords

Skin Cancer; Metastatic Melanoma; Adoptive Cell Therapy; Immunotherapy; Clinical Response

Outcome Measures

Primary Outcomes (2)

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

  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.

  2 years and 59 days

• Objective Response Rate of Patients With Metastatic Melanoma

  Objective response is defined as complete response + partial response and was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response (CR) is 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. Progressive disease (PD) is at least a 20% increase in the 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 references the smallest sum LD.

  approximately 2 years

Secondary Outcomes (1)

• Overall Survival (OS) of Patients Receiving a Lymphocyte Depleting Preparative Regimen

  up to 3 years

Study Arms (1)

Lymphocyte Depleting Prep Regimen

EXPERIMENTAL

Patients will receive a lymphocyte depleting preparative regimen of cyclophosphamide and fludarabine followed by intravenous (IV) infusion of 4-1BB selected tumor infiltrating lymphocytes (TIL) plus IV aldesleukin.

Drug: Aldesleukin; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: 4-1BB Selected Tumor Infiltrating Lymphocytes (TIL)

Interventions

Aldesleukin DRUG

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

Also known as: Proleukin

Lymphocyte Depleting Prep Regimen

Fludarabine DRUG

Fludarabine 25 mg/m\^2/day (intravenous piggyback) IVPB daily X 5 days.(The fludarabine will be started approximately 1-2 hours after the cyclophosphamide on Days -5 and -4)

Also known as: Fludara

Lymphocyte Depleting Prep Regimen

Cyclophosphamide DRUG

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

Also known as: Cytoxan

Lymphocyte Depleting Prep Regimen

4-1BB Selected Tumor Infiltrating Lymphocytes (TIL) BIOLOGICAL

On day 0, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes (one to four days after the last dose of fludarabine).

Lymphocyte Depleting Prep Regimen

Eligibility Criteria

• Age: 18 Years - 70 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. The lesion must be at least 1 cm in diameter that can be surgically removed with minimal morbidity (defined as any operation for which expected hospitalization \<less than or equal to days).
• Confirmation of diagnosis of metastatic 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.
• Greater than or equal to 18 years of age and less than or equal to age 70.
• Able to understand and sign the Informed Consent Document
• Willing to sign a durable power of attorney
• Clinical performance status of Easter Cooperative Oncology Group (ECOG) 0 or 1
• Oxygen saturation of greater than or equal to 90% on room air
• 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 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 ribonucleic acid (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

You may not qualify if:

• Prior treatment with an anti-4-1BB antibody.
• 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.
• 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

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, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am. 2000 Feb;6 Suppl 1:S11-4.

  PMID: 10685652 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

MeSH Terms

Conditions

Melanoma; Skin Neoplasms

Interventions

aldesleukin; fludarabine; fludarabine phosphate; Cyclophosphamide

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

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

steven-rosenberg@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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 9, 2014
• First Posted: April 11, 2014
• Study Start: February 21, 2014
• Primary Completion: July 21, 2016
• Study Completion: July 21, 2016
• Last Updated: September 19, 2017
• Results First Posted: September 19, 2017

Record last verified: 2017-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)