T Cell Receptor Immunotherapy Targeting NY-ESO-1 for Patients With NY-ESO-1 Expressing Cancer

NCT01967823 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 13021413-C-0214
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Background: The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients with cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying them, and then giving the cells back to the patient. In a previous study the NCI Surgery Branch used the anti-ESO-1 gene and a type of virus (retrovirus) to make these tumor fighting cells (anti-ESO-1 cells). About half of the patients who received this treatment experienced shrinking of their tumors. In this study, we are using a slightly different method of producing the anti-ESO-1 cells which we hope will be better in making the tumors shrink. Objectives: The purpose of this study is to see if these tumor fighting cells (genetically modified cells) that express the receptor for the ESO-1 molecule on their surface can cause tumors to shrink and to see if this treatment is safe. Eligibility: \- Patients 15 years old and older with cancer that has the ESO-1 molecule on their tumors. 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
• Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti ESO-1 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 anti-ESO-1 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; Meningioma; Breast Cancer; Non-Small Cell Lung Cancer; Hepatocellular Cancer

Keywords

Metastatic Cancer; Gene Therapy; Immunotherapy; Tumor Regression; Melanoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With a Response

  Percentage of patients who have a clinical response (complete response or partial response) to treatment (objective tumor regression). Response was determined entirely by radiographic imaging using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 to compare target lesions in centimeters. Complete Response is defined as disappearance of all target lesions. Partial Response is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

  6 and 12 weeks after cell infusion, then every 3 months x3, then every 6 months x 2, then per principal investigator (PI) discretion, up to five years or disease progression.

Secondary Outcomes (1)

• Percentage of T Cell Receptor (TCR) in Cluster of Differentiation 3 (CD3) + Cells

  3 and 6 months, and 1 year post cell administration

Other Outcomes (1)

• Number of Participants With Serious and Non-serious Treatment Related Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)

  Date treatment consent signed to approximately 6 weeks following cell administration.

Study Arms (1)

1/Cyclophosphamide & Fludarabine + Anti-ESO murine TCR transduced PBL + HD Aldesleukin

EXPERIMENTAL

Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + anti-ESO murine T-cell receptor (TCR) transduced PBL + high-dose (HD) aldesleukin

Biological: Anti-NY ESO-1 mTCR PBL; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldesleukin

Interventions

Anti-NY ESO-1 mTCR PBL BIOLOGICAL

Day 0: Cells will be infused intravenously (IV) on the Patient Care Unit over 20-30 minutes.

1/Cyclophosphamide & Fludarabine + Anti-ESO murine TCR transduced PBL + HD Aldesleukin

Cyclophosphamide DRUG

Days -7 and -6: Cyclophosphamide 60 mg/kg/day X 2 days intravenously (IV) in 250 mL dextrose 5% in water (D5W) infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.

Also known as: Cytoxan

1/Cyclophosphamide & Fludarabine + Anti-ESO murine TCR transduced PBL + HD Aldesleukin

Fludarabine DRUG

Days -7 to -3: Fludarabine 25 mg /m\^2/day intravenous piggy back (IVPB) daily over 30 minutes for 5 days.

Also known as: Fludara

1/Cyclophosphamide & Fludarabine + Anti-ESO murine TCR transduced PBL + HD Aldesleukin

Aldesleukin DRUG

Aldesleukin 720,000 IU/kg intravenously (IV) (based on total body weight) over 15 minutes every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum 15 doses).

Also known as: Proleukin

1/Cyclophosphamide & Fludarabine + Anti-ESO murine TCR transduced PBL + HD Aldesleukin

Eligibility Criteria

• Age: 15 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable (per Response Evaluation Criteria in Solid Tumors (RECIST) v1.0 criteria) metastatic cancer or locally advanced refractory/recurrent malignancy including melanoma that expresses ESO as assessed by one of the following methods: reverse transcription polymerase chain reaction (RT-PCR) on tumor tissue, immunohistochemistry of resected tissue, or serum antibody reactive with ESO.
• Confirmation of diagnosis of metastatic cancer including melanoma by the National Cancer Institute (NCI) Laboratory of Pathology.
• Patients must have previously received first-line standard therapy (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred.
• 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.
• More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patient's toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
• Note: Patients may have undergone minor surgical procedures within the past three weeks, as long as all toxicities have recovered to grade 1 or less.
• Note: Patients who have previously received ipilimumab and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies.
• \- Histologically proven recurrent meningioma or aggressive meningioma.
• Note: Confirmation of ESO expression and pathology is not required in patients with definitive radiologic evidence of meningioma who are unresectable, and in whom radiation therapy without biopsy is the standard treatment.
• Recurrent disease/progression after receiving all standard treatments, which must include the following:
• Surgical resection, if possible.
• Definitive radiation therapy for unresectable meningioma, or for recurrent meningioma after resection.
• At least 4 weeks post-surgery, and must be at least 3 months post-radiation therapy, with resolution of related toxicities.
• Measurable disease on magnetic resonance imaging (MRI) scan.
• No history of intracranial hemorrhage.

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.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.
• 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 cyclophosphamide, fludarabine, or aldesleukin.
• History of coronary revascularization or ischemic symptoms.
• Documented Left Ventricular Ejection Fraction (LVEF) less than or equal to 45% tested in patients:
• Age greater than or equal to 65 years
• With clinically significant atrial and/or ventricular arrhythmias, including but not limited to: atrial fibrillation, ventricular tachycardia, second- or third-degree heart block or have a history of ischemic heart disease and/or chest pain.
• Documented forced expiratory volume 1 (FEV1) less than or equal to 60% predicted tested in patients with:
• A prolonged history of cigarette smoking (greater than or equal to 20 pack-year smoking history, with cessation within the past two years).
• Symptoms of respiratory dysfunction.
• Patients who are receiving any other investigational agents.

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)

• 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

• Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, Robbins PF, Huang J, Citrin DE, Leitman SF, Wunderlich J, Restifo NP, Thomasian A, Downey SG, Smith FO, Klapper J, Morton K, Laurencot C, White DE, Rosenberg SA. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008 Nov 10;26(32):5233-9. doi: 10.1200/JCO.2008.16.5449. Epub 2008 Sep 22.

  PMID: 18809613 BACKGROUND

• Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011 Mar 1;29(7):917-24. doi: 10.1200/JCO.2010.32.2537. Epub 2011 Jan 31.

  PMID: 21282551 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Melanoma; Meningioma; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Liver Neoplasms; Neoplasm Metastasis

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; aldesleukin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Digestive System Diseases; Liver 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

Results Point of Contact

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

sar@mail.nih.gov

240-858-3080

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: October 18, 2013
• First Posted: October 23, 2013
• Study Start: October 24, 2013
• Primary Completion: April 6, 2020
• Study Completion: April 6, 2020
• Last Updated: March 24, 2021
• Results First Posted: March 24, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)