Anti-ESO (Cancer/Test Antigen) mTCR-transduced Autologous Peripheral Blood Lymphocytes and Combination Chemotherapy in Treating Patients With Metastatic Cancer That Expresses NY-ESO-1

• ClinicalTrials.gov Identifier: NCT02774291
• Recruitment Status: Unknown
• First Posted: May 17, 2016
• Last Update Posted: March 6, 2020
• Sponsor: Albert Einstein College of Medicine
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): Ira Braunschweig, Albert Einstein College of Medicine

Tracking Information

• First Submitted Date: May 13, 2016
• First Posted Date: May 17, 2016
• Last Update Posted Date: March 6, 2020
• Study Start Date: August 2016
• Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: May 16, 2016): Incidence of toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 15 years ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 16, 2016)

• In vivo survival of TCR gene-engineered cells [ Time Frame: Up to 15 years ]
  Descriptive statistics will be used to determine the in vivo survival of TCR gene-engineered cells.
• Objective response rate, graded according to RECIST criteria [ Time Frame: Up to 15 years ]
  Descriptive statistics will be used to determine the objective response rate.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Anti-ESO (Cancer/Test Antigen) mTCR-transduced Autologous Peripheral Blood Lymphocytes and Combination Chemotherapy in Treating Patients With Metastatic Cancer That Expresses NY-ESO-1
• Official Title: Pilot Study of Adoptive Cell Transfer for the Treatment of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Anti-NY ESO-1 Murine TCR-Gene Engineered Lymphocytes
• Brief Summary: This pilot clinical trial studies the side effects of anti-ESO (cancer/test antigen) murine T-cell receptor (mTCR)-transduced autologous peripheral blood lymphocytes and combination chemotherapy with cyclophosphamide and fludarabine phosphate in treating patients with cancer that has spread to other places in the body (metastatic) and expresses the gene NY-ESO-1. Donor white blood cells that are treated in the laboratory with anti-cluster of differentiation (CD)3 may help treat metastatic cancer. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) may kill more cancer cells. Aldesleukin may stimulate white blood cells, including natural killer cells, to kill metastatic cancer cells. Giving anti-ESO (cancer/test antigen) mTCR-transduced autologous peripheral blood lymphocytes together with combination chemotherapy and aldesleukin may kill more cancer cells.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety and tolerability of the administration of anti-ESO (cancer/test antigen) mTCR (T cell receptor)-engineered peripheral blood lymphocytes (anti-thyroglobulin mTCR-transduced autologous peripheral blood lymphocytes) plus high-dose aldesleukin following a nonmyeloablative lymphoid depleting preparative regimen in human leukocyte antigen (HLA)-A2 positive patients with metastatic cancer expressing the ESO antigen.

SECONDARY OBJECTIVES:

I. Determine the in vivo survival of T-cell receptor (TCR) gene-engineered cells.

II. Determine the objective response rate by Response Evaluation Criteria in Solid Tumors (RECIST) criteria.

OUTLINE:

Patients receive standard cyclophosphamide intravenously (IV) over 1 hour on days -7 to -6 and fludarabine phosphate via intravenous piggy back (IVPB) over 30 minutes on days -5 to -1 followed by anti-ESO (cancer/test antigen) mTCR-transduced autologous peripheral blood lymphocytes IV over 20-30 minutes on day 0 and aldesleukin IV over 15 minutes approximately every 8 hours on days 0-4. Patients also receive filgrastim subcutaneously (SC) on days 1-4.

After completion of study treatment, patients are followed up at 6 weeks, annually for 5 years, and then periodically for 10 years thereafter.

• Study Type: Interventional
• Study Phase: Early Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• HLA-A2 Positive Cells Present
• Metastatic Malignant Neoplasm
• Metastatic Malignant Neoplasm in the Brain

Intervention

• Biological: Aldesleukin
  Given IV
  Other Names:

  • 125-L-Serine-2-133-interleukin 2
  • Proleukin
  • r-serHuIL-2
  • Recombinant Human IL-2
  • Recombinant Human Interleukin-2
• Biological: Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes
  Given IV
  Other Name: Anti-thyroglobulin mTCR-transduced Autologous PBL
• Drug: Cyclophosphamide
  Given IV
  Other Names:

  • (-)-Cyclophosphamide
  • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  • Carloxan
  • Ciclofosfamida
  • Ciclofosfamide
  • Cicloxal
  • Clafen
  • Claphene
  • CP monohydrate
  • CTX
  • CYCLO-cell
  • Cycloblastin
  • Cycloblastine
  • Cyclophospham
  • Cyclophosphamid monohydrate
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
• Biological: Filgrastim
  Given SC
  Other Names:

  • Filgrastim XM02
  • G-CSF
  • Neupogen
  • r-metHuG-CSF
  • Recombinant Methionyl Human Granulocyte Colony Stimulating Factor
  • rG-CSF
  • Tbo-filgrastim
  • Tevagrastim
• Drug: Fludarabine Phosphate
  Given IVPB
  Other Names:

  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • Oforta
  • SH T 586
• Other: Laboratory Biomarker Analysis
  Correlative studies

Study Arms

Experimental: Treatment (mTCR, aldesleukin)

Patients receive standard cyclophosphamide IV over 1 hour on days -7 to -6 and fludarabine phosphate via IVPB over 30 minutes on days -5 to -1 followed by anti-ESO (cancer/test antigen) mTCR-transduced autologous peripheral blood lymphocytes IV over 20-30 minutes on day 0 and aldesleukin IV over 15 minutes approximately every 8 hours on days 0-4. Patients also receive filgrastim SC on days 1-4.

Interventions:

• Biological: Aldesleukin
• Biological: Anti-thyroglobulin mTCR-transduced Autologous Peripheral Blood Lymphocytes
• Drug: Cyclophosphamide
• Biological: Filgrastim
• Drug: Fludarabine Phosphate
• Other: Laboratory Biomarker Analysis

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 16, 2016): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2020
• Estimated Primary Completion Date: May 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Measurable metastatic cancer that expresses NY ESO-1 as assessed by one of the following methods: reverse transcriptase-polymerase chain reaction (RT-PCR) on tumor tissue, or by immunohistochemistry of resected tissue, or serum antibody reactive with ESO
• Confirmation of diagnosis of metastatic cancer by the Laboratory of Pathology at the Montefiore Medical Center
• Patients 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
• 3 or fewer brain metastases; 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
• More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' 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 3 weeks, as long as all toxicities have recovered to grade 1 or less or as specified in the eligibility criteria
• Eight weeks must have elapsed from the time of any antibody therapy that could affect an anti-cancer immune response, including anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA 4) therapy, at the time the patient receives the preparative regimen to allow antibody levels to decline; Note: patients who have previously received ipilimumab and have documented gastrointestinal (GI) toxicity must have a normal colonoscopy with normal colonic biopsies
• 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 must be HLA-A*0201 positive
• 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 cells are no longer detected in the blood

• 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 RT-PCR and be hepatitis C virus (HCV) ribonucleic acid (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
• Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim
• White blood cell (WBC) >= 3000/mm^3
• Platelet count >= 100,000/mm^3
• Hemoglobin > 8.0 g/dl
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< to 2.5 times the upper limit of normal
• Serum creatinine =< to 1.6 mg/dl
• Total bilirubin =< to 1.5 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl

Exclusion Criteria:

• 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, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary 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
• History of or active central nervous system (CNS) or peripheral nerve stimulation (PNS) involvement

• 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 >= 60 years old

• Pulmonary function testing in patients with:

  • A prolonged history of cigarette smoking (20 pk/yr of smoking within the past two years)
  • Symptoms of respiratory dysfunction

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 66 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02774291
• Other Study ID Numbers: 2015-5254; NCI-2015-01781 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2015-5254 ( Other Identifier: Albert Einstein College of Medicine ); P30CA013330 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Ira Braunschweig, Albert Einstein College of Medicine
• Original Responsible Party: Same as current
• Current Study Sponsor: Albert Einstein College of Medicine
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ira Braunschweig; Albert Einstein College of Medicine

• PRS Account: Albert Einstein College of Medicine
• Verification Date: March 2020