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HPV-16/18 E6/E7-Specific T Lymphocytes, Relapsed HPV-Associated Cancers, HESTIA (HESTIA)

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ClinicalTrials.gov Identifier: NCT02379520
Recruitment Status : Recruiting
First Posted : March 5, 2015
Last Update Posted : December 13, 2018
Sponsor:
Collaborators:
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Information provided by (Responsible Party):
Carlos Ramos, Baylor College of Medicine

Brief Summary:

Subjects have a type of cancer that has been associated with an infection with a virus called human papilloma virus (HPV). The cancer has come back, has not gone away after standard treatment or the subject cannot receive standard treatment.

This is a research study using special immune system cells called HPVST cells, a new experimental treatment.

Investigators want to find out if they can use this type of treatment in patients with HPV-cancers. They have discovered a way to grow large number of HPV-specific T cells from the blood of patients with HPV-cancers. They want to see if these special white blood cells, called HPVST cells, that will have been trained to kill HPV infected cells can survive in the blood and affect the tumor. They will also see if they can make the T cells more active against the HPV-cancers by engineering them to be resistant to the TGF-beta chemical that these HPV-cancers produce. They will grow these HPVST cells from the patient's blood.

The purpose of this study is to find the biggest dose of HPVSTs that is safe, to see how long they last in the body, to learn what the side effects are and to see if the HPVSTs will help people with HPV associated cancers.

If the treatment with HPVST cells alone proves safe (Group A), additional group of patients (Group B) will receive Nivolumab in addition to HPVST cells in a lymphodepleted environment. Nivolumab is an antibody therapy that helps T cells control the tumor and it is FDA approved for the treatment of certain types of cancers, including Hodgkin's lymphoma. Lymphodepletion will decrease the level of circulating T cells prior to infusion of HPVST cells, thereby giving them room to expand. The purpose of this part of the study is to find out if TGF-beta resistant HPVST cells in combination with Nivolumab are safe, how long they last in the body and if they are more effective than HPVST cells alone in controlling the tumor.


Condition or disease Intervention/treatment Phase
Human Papillomavirus-Related Carcinoma Human Papillomavirus Positive Oropharyngeal Carcinoma Human Papillomavirus Positive Cervical Carcinoma Human Papillomavirus Positive Anal Carcinoma Human Papillomavirus Positive Vulvar Carcinoma Human Papillomavirus Positive Penile Carcinoma Genetic: HPV Specific T Cells Drug: Cytoxan Drug: Fludarabine Biological: Nivolumab Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: HPV-16/18 E6/E7-Specific T Lymphocytes in Patients With Relapsed HPV-Associated Cancers
Study Start Date : September 2015
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2033

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Group A
HPV Specific T Cells
Genetic: HPV Specific T Cells

Dose escalation study with 3 dose levels: DL1-1×10^7 cells/m2, DL2-3×10^7 cells/m2, and DL3-1×10^8 cells/m2.

Group A -HPVST cells Group B -lymphodepletion & nivolumab & HPVST cells.

First, treatment in Group A will be completed for DL1 and DL2. Only if DL2 in Group A proves safe, Group B will be treated on DL2 and DL3.

Group A will be treated at DL3 only if there is excessive toxicity in cohorts treated with lymphodepletion.

HPVSTs will be given by IV injection over 1-10 minutes through a peripheral or a central line on day 0.

If patients have clinical benefit (as determined by symptoms, physical exam or radiological studies) & no significant toxicities, they may get up to 5 repeat infusions (for max total of 6 infusions) of HPVSTs at or below the same dose level.

Other Name: HPVSTs

Experimental: Group B
HPV Specific T Cells plus lymphodepletion (Cytoxan and Fludarabine) and nivolumab
Genetic: HPV Specific T Cells

Dose escalation study with 3 dose levels: DL1-1×10^7 cells/m2, DL2-3×10^7 cells/m2, and DL3-1×10^8 cells/m2.

Group A -HPVST cells Group B -lymphodepletion & nivolumab & HPVST cells.

First, treatment in Group A will be completed for DL1 and DL2. Only if DL2 in Group A proves safe, Group B will be treated on DL2 and DL3.

Group A will be treated at DL3 only if there is excessive toxicity in cohorts treated with lymphodepletion.

HPVSTs will be given by IV injection over 1-10 minutes through a peripheral or a central line on day 0.

If patients have clinical benefit (as determined by symptoms, physical exam or radiological studies) & no significant toxicities, they may get up to 5 repeat infusions (for max total of 6 infusions) of HPVSTs at or below the same dose level.

Other Name: HPVSTs

Drug: Cytoxan
500mg/m^2/day x 3 days (on days -4, -3 and -2)
Other Name: cyclophosphamide

Drug: Fludarabine
30mg/m^2/day x 3 days (on days -4, -3, and -2)
Other Name: Fludara

Biological: Nivolumab
240mg every 2 weeks (+/- 3 days) starting on day -1
Other Name: Opdivo




Primary Outcome Measures :
  1. Number of patients with dose limiting toxicity (DLT) [ Time Frame: 6 weeks ]

    DLT will be defined as any toxicity that is irreversible or life threatening, defined as the following, considered to be possibly, probably, or definitely related to the HPVST injection.

    1. Non-hematologic DLT is any grade 3 or grade 4 non-hematologic toxicity.
    2. Hematologic DLT is defined as any grade 4 hematologic toxicity.


Secondary Outcome Measures :
  1. Overall response rate [ Time Frame: 6 weeks ]
    To measure anti-tumor effects of HPV-specific T lymphocytes



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

PROCUREMENT

  1. Diagnosis of a cancer for which the presence of a high risk HPV type has been documented in a biopsy sample
  2. Cancer is:

    • recurrent or persistent after standard therapy
    • OR patient is unable to receive standard therapy
  3. Karnofsky score ≥ 50%
  4. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent

TREATMENT

  1. Diagnosis of a cancer for which the presence of a high risk HPV type has been documented in a biopsy sample
  2. Cancer is:

    • recurrent or persistent after standard therapy
    • OR patient is unable to receive standard therapy
  3. Life expectancy ≥ 6 weeks.
  4. Age ≥ 18 years.
  5. Karnofsky score ≥ 50%
  6. Bilirubin < 3 × upper limit of normal (ULN), AST < 5 × ULN, Hgb ≥ 7.0 g/dL
  7. Pulse oximetry of > 90% on room air.
  8. GFR > 30 mL/min calculated by the Cockcroft-Gault, MDRD study, or CKD-EPI creatinine equations, or equivalent
  9. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent
  10. Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.

Exclusion Criteria:

PROCUREMENT

1. Known HIV positivity.

TREATMENT

  1. Currently receiving any investigational agents or have received any tumor vaccines or T cell antibodies within previous 4 weeks.
  2. Severe intercurrent infection.
  3. Pregnancy or lactation.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02379520


Contacts
Contact: Carlos Ramos, MD 832-824-4817 caramos@bcm.edu
Contact: Vicky Torrano, RN 832-824-7821 vtorrano@bcm.edu

Locations
United States, Texas
Houston Methodist Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Carlos A Ramos, MD    832-824-4817    caramos@bcm.edu   
Contact: Vicky Torrano    832-824-7821    vtorrano@bcm.edu   
Sponsors and Collaborators
Baylor College of Medicine
Center for Cell and Gene Therapy, Baylor College of Medicine
The Methodist Hospital System
Investigators
Principal Investigator: Carlos Ramos, MD Baylor College of Medicine

Responsible Party: Carlos Ramos, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT02379520     History of Changes
Other Study ID Numbers: H-36021 HESTIA
First Posted: March 5, 2015    Key Record Dates
Last Update Posted: December 13, 2018
Last Verified: December 2018

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

Keywords provided by Carlos Ramos, Baylor College of Medicine:
recurrent cancer
refractory cancer
virus specific T-cells
gene therapy
HPV

Additional relevant MeSH terms:
Oropharyngeal Neoplasms
Anus Neoplasms
Vulvar Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Physiological Effects of Drugs
Carcinoma
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases
Vulvar Diseases
Genital Diseases, Female
Cyclophosphamide