Study Stopped
A more highly selected protocol with ESO TCR opened for pts with melanoma
Chemotherapy Followed by ESO-1 Lymphocytes and Aldesleukin to Treat Metastatic Cancer
Phase II Study of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Anti-NY ESO-1 TCR-Gene Engineered Lymphocytes
2 other identifiers
interventional
45
1 country
1
Brief Summary
Background:
- This study uses an experimental cancer treatment that uses the patient s own lymphocytes (type of white blood cell), which are specially selected and genetically modified to target and destroy their tumor. Objectives:
- To test the safety of the treatment and determine if it can cause the patient s tumor to shrink. Eligibility:
- Patients greater than 18 years and less than or equal to 66 years of age whose cancer has spread beyond the original site and does not respond to standard treatment.
- Patients have tissue type human leukocyte antigen (HLA)-A\*0201.
- Patients cancer cells have the ESO-1 gene. Design:
- Workup: Patients have scans, x-rays, laboratory tests, and other tests as needed.
- Patients have leukapheresis to collect cells for laboratory treatment and later reinfusion. For this procedure, whole blood is collected thorough a tube in a vein, the desired cells are extracted from the blood, and the rest of the blood is returned to the patient.
- Chemotherapy: Patients have low-dose chemotherapy for 1 week to prepare the immune system to receive the treated lymphocytes.
- Cell infusion and aldesleukin (IL-2) treatment: Patients receive the lymphocytes by a 30-minute infusion through a vein. Starting within 24 hours of the infusion, they receive high-dose aldesleukin infusions every 8 hours for up to 5 days (maximum15 doses).
- Recovery: Patients rest for 1 to 2 weeks to recover from the effects of chemotherapy and aldesleukin.
- Tumor biopsy: Patients may be asked to undergo a biopsy (surgical removal of a small piece of tumor) after treatment to look at the effects of treatment on the immune cells in the tumor.
- Follow-up: After treatment is completed, patients return to the clinic once a month for several months for physical examinations, a review of side effects, laboratory tests and scans. They may undergo leukapheresis at some visits to look at the effect of treatment on the immune system and check the viability of the infused cells. Patients then return to the National Institute of Health (NIH) clinic once a year for 5 years and then complete a follow-up questionnaire for another 10 years.
- Retreatment: Patients whose tumor shrinks or disappears following treatment and then recurs may receive one additional treatment, using the same regimen of chemotherapy, lymphocyte infusion and IL-2 treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started May 2008
Longer than P75 for phase_2
1 active site
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
First Submitted
Initial submission to the registry
May 1, 2008
CompletedFirst Posted
Study publicly available on registry
May 2, 2008
CompletedStudy Start
First participant enrolled
May 29, 2008
CompletedResults Posted
Study results publicly available
June 27, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 29, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
June 29, 2016
CompletedNovember 19, 2019
November 1, 2019
8.1 years
May 1, 2008
May 19, 2016
November 6, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Clinical Response Per the Response Evaluation Criteria in Solid Tumors (RECIST)
Response was determined by the RECIST. 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 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 references the smallest sum LD.
Approximately 3 years
Secondary Outcomes (2)
Number of Participants With In Vivo Survival of T-Cell Receptor (TCR)-Engineered Cells
1 month post treatment
Number of Participants With Serious and Non-Serious Adverse Events
Date treatment consent signed to date off study, approximately, 66 months and 10 days
Study Arms (4)
#1 Anti-NY-ESO-1 TCR PBL+HD IL-2 Mel/RCC
EXPERIMENTALPatients with melanoma or renal cell cancer (RCC) will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin.
#2 Anti-NY-ESO-1 TCR PBL+HD IL-2 OtherCa
EXPERIMENTALPatients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 TCR PBL and high dose (HD) aldesleukin
#3ESO1 TCR PBL+ALVAC ESO1+HD IL2 Mel/RCC
EXPERIMENTALPatients with melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by replication-defective recombinant canarypox virus (ALVAC) NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
#4ESO1 TCR PBL+ALVAC ESO1+HD IL2 OtherCa
EXPERIMENTALPatients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by ALVAC NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
Interventions
Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 T-cell receptor (TCR) peripheral blood lymphocytes (PBL) and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Patient Care Unit over 20-30 minutes.
Aldesleukin 720,000 IU/kg intravenous (IV) (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days(maximum of 15 doses)
Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml dextrose 5% in water (D5W) with Mesna 15 mg/kg/day X 2 days over 1 hr.
Fludarabine 25 mg/m2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.
Approximately two hours prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10e7 cell culture infectious dose 50 (CCID50) (with a range of approximately 10e6.4 to 10e7.9 / mL) of the ESO-1 ALVAC virus S.C. in each extremity (total of 4 x 10e7 CCID50/2 mL.
Eligibility Criteria
You may qualify if:
- Metastatic cancer that expresses ESO as assessed by one of the following methods: reverse transcription-polymerase chain reaction (RT-PCR) on tumor tissue, or by immunohistochemistry of resected tissue, or serum antibody reactive with ESO. Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the National Cancer Institute (NCI).
- Patients with histologies other than metastatic melanoma, must have previously received systemic standard care (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.
- Greater than or equal to 18 years of age. and less than or equal to 66 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 for four months after receiving the preparative regimen.
- Patients must be human leukocyte antigen (HLA)-A\*0201 positive
- 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 hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by RT-PCR and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
- Hematology:
- Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim.
- White blood cell (WBC) (greater than 3000/mm(3)).
- +9 more criteria
You may not qualify if:
- Prior vaccination with an replication-defective recombinant canarypox virus (ALVAC) containing vaccine for patients who will receive the ALVAC ESO-1 vaccine (cohorts 3 or 4).
- 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.
- 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.
- Known systemic hypersensitivity to any of the vaccine components, including egg products or Neomycin for patients who will receive the ALVAC ESO-1 vaccine (cohorts 3 or 4).
- 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 percent.
- Documented forced expiratory volume (LVEF) of less than or equal to 45 percent tested in patients with:
- History of ischemic heart disease, chest pain, or 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 in 1 second (FEV1) less than or equal to 60 percent predicted tested in patients with:
- A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).
- +1 more criteria
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
Related Publications (4)
Zeng G, Touloukian CE, Wang X, Restifo NP, Rosenberg SA, Wang RF. Identification of CD4+ T cell epitopes from NY-ESO-1 presented by HLA-DR molecules. J Immunol. 2000 Jul 15;165(2):1153-9. doi: 10.4049/jimmunol.165.2.1153.
PMID: 10878395BACKGROUNDZhao Y, Bennett AD, Zheng Z, Wang QJ, Robbins PF, Yu LY, Li Y, Molloy PE, Dunn SM, Jakobsen BK, Rosenberg SA, Morgan RA. High-affinity TCRs generated by phage display provide CD4+ T cells with the ability to recognize and kill tumor cell lines. J Immunol. 2007 Nov 1;179(9):5845-54. doi: 10.4049/jimmunol.179.9.5845.
PMID: 17947658BACKGROUNDValmori D, Dutoit V, Lienard D, Rimoldi D, Pittet MJ, Champagne P, Ellefsen K, Sahin U, Speiser D, Lejeune F, Cerottini JC, Romero P. Naturally occurring human lymphocyte antigen-A2 restricted CD8+ T-cell response to the cancer testis antigen NY-ESO-1 in melanoma patients. Cancer Res. 2000 Aug 15;60(16):4499-506.
PMID: 10969798BACKGROUNDCrompton JG, Sukumar M, Roychoudhuri R, Clever D, Gros A, Eil RL, Tran E, Hanada K, Yu Z, Palmer DC, Kerkar SP, Michalek RD, Upham T, Leonardi A, Acquavella N, Wang E, Marincola FM, Gattinoni L, Muranski P, Sundrud MS, Klebanoff CA, Rosenberg SA, Fearon DT, Restifo NP. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics. Cancer Res. 2015 Jan 15;75(2):296-305. doi: 10.1158/0008-5472.CAN-14-2277. Epub 2014 Nov 28.
PMID: 25432172DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Steven A. Rosenberg
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Steven A Rosenberg, M.D.
National Cancer Institute (NCI)
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
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
May 1, 2008
First Posted
May 2, 2008
Study Start
May 29, 2008
Primary Completion
June 29, 2016
Study Completion
June 29, 2016
Last Updated
November 19, 2019
Results First Posted
June 27, 2016
Record last verified: 2019-11
Data Sharing
- IPD Sharing
- Will not share