Open Actively Recruiting

Genetically Engineered PBMC and PBSC Expressing NY-ESO-1 TCR After a Myeloablative Conditioning Regimen to Treat Patients With Advanced Cancer


Brief Summary

The purpose of this phase 1 study is to investigate a new approach in the treatment of cancer, i.e. giving gene-modified immune cells combined with gene-modified stem cells intravenously to reprogram the immune system to attempt to fight the cancer. The goal is to teach the immune system to recognize and kill cancer cells that have the NY-ESO-1 protein with sustained killing activity. The gene-modified cells studied in this experimental protocol are the patient s own white blood cells and stem cells from blood that will be modified in the laboratory using genetic techniques to express the NY-ESO-1 TCR against cancer cells. The gene modification of the white blood cells is an attempt to direct the patient s own immune cells to kill cancer cells. Since these immune cells usually only last for a few months in the body before they die, stem cells will be gene-modified so that the patient s body can attempt to create new immune cells that will kill cancer cells. Gene modification of cells involves the transfer of foreign genetic material (DNA) into a cell, in this case the patient s immune system cells and stem cells. This process will endow the recipient immune cells and descendants of the stem cells with the ability to eliminate cancer cells that express the cancer specific protein, NY-ESO-1. The specific receptor against cancer cells that will be transferred to the immune cells and stem cells is called NY-ESO-1 T cell receptor (or TCR). In this study, the gene-modified immune cells will be given in combination with the gene-modified stem cells to all patients to test the safety, toxicity and tumor responses of administering this combination. The study procedures will start with the collection of stem cells by administering medicines to mobilize the stem cells from the bone marrow and deposit them in the peripheral blood and using a medical device called a blood cell separator. A cell separator will also be used to collect white blood cells. These cells will be grown in the laboratory and then genetically modified with a virus vector (lentivirus vector for stem cells and retrovirus vector for lymphocytes), extensively modified to make sure that it is not infectious. The lentivirus and retrovirus vectors will allow expression of NY-ESO-1 TCR on the surface of cancer cells which directs the immune system to recognize cancer as foreign and kill the cancer cells. The lentivirus will also carry a second gene, Herpes Simplex Virus 1 (HSV1) sr39 thymidine kinase (TK) reporter gene, which will allow the progeny gene modified immune cells to be visualized when a PET scan is performed. The TCR gene modified cells will be tested to make sure that they are not contaminated with bacteria and other organisms, and that they express the appropriate TCR. The stem cells will be frozen prior to administration and the lymphocytes will be administered fr

Primary Purpose
Study Type
Phase I


Healthy Volunteers
Minimum Age
16 Years
Maximum Age

Subjects who have advanced cancer that has spread to other areas of your body and has not responded to standard approved therapies.
For more information about the eligibility criteria for this trial, refer to the Health Professional version.

Inclusion Criteria:

  • Stage IV or locally advanced unresectable cancers for which no alternative therapies with proven survival advantage are available
  • NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commercially available NY-ESO-1 antibodies
  • HLA-A*0201 (HLA-A2.1) positivity by molecular subtyping
  • Age greater than or equal to 16 years old; if patients 16-17 years old are enrolled in the trial, they will only be enrolled after 3 patients >= 18 years old have been treated, and the treatment has been shown to be safe
  • A minimum of one measurable lesion defined as:
    • Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
    • Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Adequate bone marrow and major organ function to undergo a PBSC transplant determined within 30-60 days prior to enrollment using standard phase 1 criteria for organ function defined as:
    • Absolute neutrophil count (ANC) >= 1.5 x 10^9 cells/L
    • Platelets >= 100 x 10^9/L
    • Hemoglobin >= 9 g/dL
    • Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x ULN (upper limit of normal) (=< 5 x ULN, if documented liver metastases are present)
    • Total bilirubin =< 2 x ULN (except patients with documented Gilbert?s syndrome)
    • Creatinine < 2 mg/dl (or a glomerular filtration rate > 60)
  • Must be willing and able to accept at least three leukapheresis procedures
  • Must be willing and able to undergo three research PET scans
  • Must be willing and able to provide written informed consent

Exclusion Criteria:

  • Inability to purify >= 2.5 x 10^6 CD34-enriched cells/kg of patient weight from the pooled G-CSF mobilized leukapheresis products
  • Previously known hypersensitivity to any of the agents used in this study; known sensitivity to busulfan or fludarabine
  • Received systemic treatment for cancer, including immunotherapy, within 28 days prior to initiation of conditioning chemotherapy administration within this protocol
  • Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 2 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed)
  • Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
  • Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments; if there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist
  • Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol
  • Known clinically active brain metastases; prior evidence of brain metastasis successfully treated with surgery or radiation therapy will not be exclusion for participation as long as they are deemed under control at the time of study enrollment and there are no neurological signs of potential brain metastases
  • Pregnancy or breast-feeding; female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and for 6 months afterwards; all female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 14 days from starting the conditioning chemotherapy; the definition of effective contraception will be based on the judgment of the study investigators
  • Since IL-2 is administered following cell infusion:
    • Patients will be excluded if they have a history of clinically significant electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia with evidence of ischemia on a cardiac stress test (stress thallium, stress multigated acquisition [MUGA], dobutamine echocardiogram or other stress test)
    • Similarly, patients with a baseline left ventricular ejection fraction (LVEF) < 45% will be excluded.
    • Patients with ECG results of any conduction delays (PR interval > 200 ms, corrected QT [QTC] > 480 ms), sinus bradycardia (resting heart rate < 50 beats per minute), sinus tachycardia (heart rate >120 beats per minute) will be evaluated by a cardiologist prior to starting the trial; patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as > 20 premature ventricular contractions [PVCs] per minute), ventricular tachycardia or 3rd degree heart block will be excluded from the study unless cleared by a cardiologist
    • Patients with pulmonary function test abnormalities as evidenced by a (forced expiratory volume 1 [FEV1]/forced vital capacity [FVC ] < 70% of predicted for normality will be excluded
  • Bone marrow involvement based on PET/CT scan at screening
  • Active or recent herpes simplex virus (HSV) infection or cytomegalovirus (CMV) based on symptoms with positive swab culture and/or positive IgM (immunoglobulin M) screening
  • Liver metastases with no other metastatic sites

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Study Stats
Protocol No.
Bladder Cancer
Breast Cancer
Cervical Cancer
Colorectal Cancer
Esophageal Cancer
Gallbladder Cancer
Head and Neck Cancer
Kidney Cancer
Liver Cancer
Lung Cancer
Melanoma (Skin Cancer)
Other Cancer
Ovarian Cancer
Pancreatic Cancer
Prostate Cancer
Stomach Cancer
Uterine/Endometrial Cancer
  • UCLA Westwood
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