Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Digestive System Diseases

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Uterine Cervical Neoplasms

Adenoma

Vaginal Neoplasms

Anus Neoplasms

Oropharyngeal Neoplasms

Penile Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Rectal Neoplasms

Colorectal Neoplasms

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Intestinal Diseases

Anus Diseases

Rectal Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Vaginal Diseases

Genital Neoplasms, Male

Genital Diseases, Male

Penile Diseases

Male Urogenital Diseases

Vaginal Cancer

Penile Cancer

Anal Cancer

Antineoplastic Agents

Antirheumatic Agents

All Drugs and Chemicals

Anti-Infective Agents

Cyclophosphamide

Fludarabine

Fludarabine phosphate

Aldesleukin

Immunomodulating Agents

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Anti-HIV Agents

Anti-Retroviral Agents

Antiviral Agents

patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin

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)

E6 TCR

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).

Christian S Hinrichs, M.D.

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.

BACKGROUND:

* Metastatic or refractory/recurrent human papillomavirus (HPV)-16+ cancers (cervical, vulvar, vaginal, penile, anal, and oropharyngeal cancers) are incurable and poorly palliated by standard therapies.
* HPV-16+ cancers constitutively express the HPV-16 E6 oncoprotein, which is absent from healthy human tissues.
* Administration of T cell receptor (TCR) gene engineered T cells can induce objective tumor responses in certain malignancies.
* T cells genetically engineered with a TCR targeting HPV-16 E6 (E6 TCR) display specific reactivity against human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2+), HPV-16+ target cells.

OBJECTIVES:

Primary Objective

* To determine a safe dose of administration of autologous T cells transduced with an anti-HPV-16 E6 TCR and aldesleukin to patients following a nonmyeloablative but lymphodepleting preparative regimen.
* To determine the objective tumor response rate (Complete or Partial Response) and duration in patients with metastatic or recurrent/refractory HPV-16+ cancers treated with this regimen.

ELIGIBILITY:

* Patients greater than or equal to 18 years old and less than or equal to 70 years old with metastatic or refractory/recurrent HPV-16+ cancer.
* Prior first line systemic therapy is required unless the patient declines standard treatment.
* Patients must be HLA-A 02:01-positive.

DESIGN:

* Patients will receive a non-myeloablative lymphocyte-depleting preparative regimen of cyclophosphamide and fludarabine
* On day 0 patients will receive transduced lymphocytes and then begin high dose aldesleukin
* The study will begin with a phase I dose escalation. After the maximum tolerated dose (MTD) cell dose has been determined, the patients will be enrolled into the phase II portion of the study.
* Clinical and immunologic response will be evaluated about 4 to 6 weeks after treatment and then about every 1-6 months until disease progression
* Following a dose escalation phase of 9 to 18 patients, initially 21 evaluable patients will be enrolled in the phase II portion of the study. If 0 to 1 of the 21 patients experiences a clinical response, then no further patients will be enrolled. If 2 or more of the first 21 evaluable patients enrolled have a clinical response, then accrual will continue until a total of 41 evaluable patients have been enrolled. The accrual ceiling will be set at 61 patients. Provided that about 1 patient every 6 weeks will be enrolled onto this trial, approximately 4 years may be needed to accrue the maximum number of patients.

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

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.

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.

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.

Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria in Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

A dose limiting toxicity is all Grade 3 and greater toxicities with the exception of myelosuppression, defined as lymphopenia, neutropenia, decreased hemoglobin, and thrombocytopenia, due to chemotherapy preparative regimen. Aldesleukin expected toxicities as defined in Appendix 2 and 3 of the protocol. Expected chemotherapy toxicities as defined in the pharmaceutical information section. Immediate hypersensitivity reactions (excluding symptomatic bronchospasm and grade 4 hypotension) occurring within 2 hours of cell infusion (related to cell infusion) that are reversible to a grade 2 or less within 24 hours of cell administration with standard therapy. Grade 3 fever. Events that are clearly related to the patient's disease.

Detection of E6 TCR T cells in patients peripheral blood leukocytes (PBL)/apheresis samples by flow cytometry.

Presence of PD-1 on circulating lymphocytes by flow cytometry one month after treatment.

National Cancer Institute (NCI)

Principal Investigator

patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin

Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.

Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days

E6 TCR: 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: 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).

HPV-16 E6 mTCR PBL 1x10^9 + HD IL-2

HPV-16 E6 mTCR PBL 1x10^10 + HD IL-2

HPV-16 E6 mTCR PBL 1x10^11 + HD IL-2

HPV-16 E6 mTCR PBL >1x10^11 up to 2x10^11 + HD IL-2

HPV-16 E6 mTCR PBL MTD + HD IL-2

HPV-16 E6 mTCR PBL MTD + HD IL-2-Retreatment

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Baseline Cancer Types

Dr. Christian Hinrichs

All treated subjects who received at least one dose of human papilloma virus (HPV)-16 E6 monoclonal T cell receptor (mTCR) peripheral blood lymphocytes (PBL) 1x10\^9, 1x10\^10,1x10\^11, \>1x10\^11 up to 2x10\^11 + high-dose (HD) interleukin 2 (IL-2) were included.

All Treated Subjects

Maximum Tolerated Dose (MTD)

Complete Response (CR)

Partial Response (PR)

Objective Tumor Response Rate (Complete or Partial Response)

Duration of Response

Number of Participants With Serious and Non-serious Adverse Events

Number of Participants With a Dose Limiting Toxicity (DLT)

Responders

Non-responders

One patient in group HPV-16 E6 mTCR PBL 1x10\^10 + HD IL-2 did not have research blood collected at one month post infusion, and thus could not examine the cells for that patient at that time point.

Percentage of Cluster of Differentiation 3 (CD3+) Cells That Are E6 T-Cell Receptor Memory of Circulating T-Cells in Responders and Non-responders

Expression of Programmed Cell Death 1 (PD-1) by Circulating E6 T-Cell Receptor (TCR) T-Cells

This is the phase 2 arm that was treated at the MTD determined in the phase 1 portion.

patients will receive cyclophosphamide and fludarabine followed by infusion of the human papilloma virus (HPV) E6 T cell receptor (TCR), followed by high dose aldesleukin

Fludarabine: Patients will receive Fludarabine 25 mg/m\^2/day for 5 days.

Cyclophosphamide: Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days

E6 TCR: 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: 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).

Drug Administration

Retreated at the MTD

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
T Cell Receptor Immunotherapy Targeting HPV-16 E6 for HPV-Associated Cancers	NCT02280811	Vaginal Cancer Cervical Cancer Anal Cancer Penile Cancer Oropharyngeal C...	Fludarabine Cyclophosphamid... E6 TCR Aldesleukin	18 Years - 70 Years	National Institutes of Health Clinical Center (CC)
T Cell Receptor Immunotherapy Targeting HPV-16 E6 for HPV-Associated Cancers	NCT02280811	Vaginal Cancer Cervical Cancer Anal Cancer Penile Cancer Oropharyngeal C...	Fludarabine Cyclophosphamid... E6 TCR Aldesleukin	18 Years - 70 Years	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for e6 tcr

Every month we try and update this database with for e6 tcr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for e6 tcr

Every month we try and update this database with for e6 tcr cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for e6 tcr cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.