T Cell Receptor Immunotherapy Targeting HPV-16 E6 for HPV-Associated Cancers
A Phase I/II Study of T Cell Receptor Gene Therapy Targeting HPV-16 E6 for HPV-Associated Cancers
2 other identifiers
interventional
12
1 country
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 these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. Researchers want to test this on human papilloma virus (HPV)-associated cancers. Objective: \- The purpose of this study is to determine a safe number of these cells to infuse and to see if these particular tumor-fighting cells (Anti-HPV E6) can shrink tumors associated with HPV and test the toxicity of this treatment. Eligibility: \- Adults age 18-66 with an HPV-16-associated cancer. 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 HPV E6 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 HPV E6 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Oct 2014
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 14, 2014
CompletedFirst Submitted
Initial submission to the registry
October 30, 2014
CompletedFirst Posted
Study publicly available on registry
November 3, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 28, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
June 28, 2016
CompletedResults Posted
Study results publicly available
August 2, 2017
CompletedSeptember 6, 2017
August 1, 2017
1.7 years
October 30, 2014
June 8, 2017
August 7, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Maximum Tolerated Dose (MTD)
The MTD is the highest dose at which ≤1 of 6 patients experienced a dose limiting toxicity (DLT) or the highest dose level studied if DLTs are not observed at any of the dose levels.
participants were followed for the duration of hospital stay, an average of 3 weeks
Objective Tumor Response Rate (Complete or Partial Response)
Objective tumor response rate is defined as the number of participants with a complete or partial response per the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.
4 years
Duration of Response
Duration of response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response is disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Progression is at least a 20% increase in the sum of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
up to one year
Secondary Outcomes (4)
Number of Participants With Serious and Non-serious Adverse Events
19 months and 7 days
Number of Participants With a Dose Limiting Toxicity (DLT)
19 months and 7 days
Percentage of Cluster of Differentiation 3 (CD3+) Cells That Are E6 T-Cell Receptor Memory of Circulating T-Cells in Responders and Non-responders
One month after treatment
Expression of Programmed Cell Death 1 (PD-1) by Circulating E6 T-Cell Receptor (TCR) T-Cells
one month after treatment
Study Arms (1)
T Cell Receptor Immunotherapy
EXPERIMENTALpatients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin
Interventions
Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.
Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days
On day 0, cells will be infused intravenously (IV) over 20-30 minute (between 1 and 4 days after the last dose of fludarabine)
Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).
Eligibility Criteria
You may qualify if:
- Measurable metastatic or refractory/recurrent human papilloma virus (HPV-16+) cancer (determined by in situ hybridization (ISH) or a polymerase chain reaction (PCR)-based test).
- Patients must be human leukocyte antigens (HLA-A) 02:01-positive.
- All patients must have received prior first line standard therapy or declined standard therapy, 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.
- Greater than or equal to 18 years of age and less than or equal to 70 years of age.
- Able to understand and sign the Informed Consent Document.
- Willing to sign durable power of attorney
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Life expectancy of greater than 3 months.
- Patients of both genders must be willing to practice birth control from the time of enrollment on this study up to 4 months after treatment. Patients must be willing to undergo testing for HPV-16 prior to becoming pregnant.
- Women of child bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
- 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 are 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 the 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.
- Hematology:
- +9 more criteria
You may not qualify if:
- Women of childbearing potential who are pregnant or breastfeeding. There are potentially dangerous side effects of the treatment on the fetus or infant.
- Active systemic infections (for e.g.: requiring anti-infective treatment), 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 cyclophosphamide or fludarabine.
- History of coronary revascularization or ischemic symptoms.
- Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% tested. The following patients will undergo cardiac evaluations
- a. clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or
- b. age greater than or equal 60 years old
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 (3)
Rosenberg SA. Raising the bar: the curative potential of human cancer immunotherapy. Sci Transl Med. 2012 Mar 28;4(127):127ps8. doi: 10.1126/scitranslmed.3003634.
PMID: 22461638BACKGROUNDHinrichs CS, Rosenberg SA. Exploiting the curative potential of adoptive T-cell therapy for cancer. Immunol Rev. 2014 Jan;257(1):56-71. doi: 10.1111/imr.12132.
PMID: 24329789BACKGROUNDChaturvedi AK, Engels EA, Pfeiffer RM, Hernandez BY, Xiao W, Kim E, Jiang B, Goodman MT, Sibug-Saber M, Cozen W, Liu L, Lynch CF, Wentzensen N, Jordan RC, Altekruse S, Anderson WF, Rosenberg PS, Gillison ML. Human papillomavirus and rising oropharyngeal cancer incidence in the United States. J Clin Oncol. 2011 Nov 10;29(32):4294-301. doi: 10.1200/JCO.2011.36.4596. Epub 2011 Oct 3.
PMID: 21969503BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Christian Hinrichs
- Organization
- National Cancer Institute
Study Officials
- PRINCIPAL INVESTIGATOR
Christian S Hinrichs, M.D.
National Cancer Institute (NCI)
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- 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 30, 2014
First Posted
November 3, 2014
Study Start
October 14, 2014
Primary Completion
June 28, 2016
Study Completion
June 28, 2016
Last Updated
September 6, 2017
Results First Posted
August 2, 2017
Record last verified: 2017-08
Data Sharing
- IPD Sharing
- Will not share