Clinical Trial: HPV-16/18 E6/E7-Specific T Lymphocytes, Relapsed HPV-Associated Cancers, HESTIA

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: HPV-16/18 E6/E7-Specific T Lymphocytes in Patients With Relapsed HPV-Associated Cancers

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

Detailed Summary:

HPV is found in the cancer cells of more than half the patients with certain types of cancer, suggesting that it may play a role in causing the cancer. The virus makes proteins in the tumor cells that should allow the diseased cells to be recognized and killed by a part of the body's own immune system called T cells. Unfortunately, tumors are able to avoid being killed by making molecules that turn off these T cells. So, the cancer cells infected by HPV are able to hide from the body's immune system and escape destruction.

The investigators have previously studied cancers caused by a different virus, called Epstein-Barr virus (EBV). These EBV-cancers are like HPV-cancers, since they turn off the T cells that would otherwise destroy them, and so can keep growing. They investigators have found, however, that if they removed the T cells from the blood of patients with EBV-cancers and grew them outside the body, they could increase the number and the activity of T cells directed against the tumors. When these T cells were given back to the patients, the T cells eliminated the cancers in over half the recipients. Investigators also found that they could engineer the T cells to be even more active against the EBV-cancer cells by making them resist an inhibitory chemical called TGF-beta, which is produced by these cancer cells.

Investigators will collect up to 240 mL of blood. Then they will use this blood to grow T cells. First they will grow them in a special type of cell called a dendritic cell, which stimulates the T cells. These dendritic cells will then be loaded with bits of proteins from the HPV virus called E6 and E7. These dendritic cells will be used to stimulate T cells. This stimulation trains the T cells to kill cells with the HPV proteins E6 and E7 on their surface. Next, the investigators will grow these HPV-speci
Sponsor: Baylor College of Medicine

Current Primary Outcome: Number of Patients with 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of HPVST cells in Blood [ Time Frame: 6 weeks ]
  • Number of HPVST cells in Blood [ Time Frame: 1 year ]
  • Number of Patients with Tumor Response [ Time Frame: 6 weeks ]
  • Number of HPVSTs in the blood that have been transduced with a dominant-negative receptor for TGFβ [ Time Frame: 6 weeks ]
  • Number of HPVSTs in the blood that have been transduced with a dominant-negative receptor for TGFβ [ Time Frame: 1 year ]


Original Secondary Outcome: Same as current

Information By: Baylor College of Medicine

Dates:
Date Received: February 25, 2015
Date Started: September 2015
Date Completion: October 2033
Last Updated: February 2, 2017
Last Verified: February 2017