Trial Information

Phase I/II Study of the Administration of Multi-Virus-Specific Cytotoxic T Lymphocytes Expressing CD19 Chimeric Receptors for Prophylaxis or Therapy of Relapse of CD19 Positive Malignancies Post Hematopoietic Stem Cell Transplantation

The donor gave us blood to make CD19 chimeric receptor trivirus specific T cells in the
laboratory. These cells were grown and frozen for the subject. To make these special T cells
we grow them with stimulator cells. Stimulator cells are also made from the donor's blood
but they are irradiated so that they can no longer grow. Stimulator cells have been infected
with viruses so that they carry proteins from 3 viruses (CMV, adenovirus, and EBV). These
cells are cultured with the T cells so that they can learn to see and attack cells infected
with CMV, EBV and adenovirus.

To get the CD19 antibody to attach to the surface of the T cell, we inserted the antibody
gene into the T cell. This is done with a virus called a retrovirus that has been made for
this study and will carry the antibody gene into the T cell. This virus also helps us find
the T cells in the blood after we inject them. Once we make sufficient numbers of T cells we
freeze the cells and test them to make sure they kill CD19+ tumors cells and cells infected
with CMV, EBV and adenovirus. Once testing is completed the cells will be ready to give to
the subject.

Because the subject will have received cells with a new gene in them the subject will be
followed for a total of 15 years to see if there are any long term side effects of gene
transfer.

When the subjects enroll on this study, they will be assigned a dose of CD19 chimeric
receptor trivirus specific T cells.

The subject will be given an injection of cells into the vein through an IV line at the
assigned dose. Before the subjects receive the injection, they may be given a dose of
diphenhydramine (Benadryl) and acetaminophen (Tylenol). The injection will take about 20
minutes. We will follow the subject in the clinic after the injection for up to 3 hours. The
treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital
or The Methodist Hospital.

Medical tests before treatment—

Before being treated, the subject will receive a series of standard medical tests:

Physical exam Blood tests to measure blood cells, kidney and liver function.

Medical tests during and after treatment—

The subject will receive standard medical tests when they are getting the infusions and
after:

Physical exams Blood tests to measure blood cells, kidney and liver function.

To learn more about the way the CD19 chimeric receptor trivirus specific T cells are working
and how long they last in the body, extra blood will be drawn.

This blood may be drawn from a central line if the subject has one. On the day the subject
receives the cells, blood will be taken before the cells are given and 3 hours afterwards.
Other blood will be drawn one week, 2 weeks, 4 weeks, 6 weeks and 8 weeks after the
infusion, then at Months 3, 6, 9 and 12. Then blood will be drawn every 6 months for 4
years, then yearly for a total of 15 years (up to 30 blood collections). If the subject
receives the cells at a time when sensitive tests indicate relapse or a high risk of
relapse, they will have additional reviews and blood tests to monitor these tests and look
for relapse.

The total blood drawn during the participation in this study will not exceed 300 teaspoons.
No more than 10 teaspoons or 1/2 teaspoon per 2.2 pounds of body weight (whichever is
lesser) will be drawn at each collection. This volume is considered safe, but may be
decreased if the subject has a low red blood cell count (anemic).

If the subject has bone marrow studies in the first year after completing treatment on this
study, we may ask to have a sample (about 1 teaspoon) of bone marrow to look for CD19
chimeric receptor T cells for research purposes.

Patients will receive supportive care for acute or chronic toxicity, including blood
components or antibiotics, and other intervention as appropriate.

For subjects receiving the CTLs for treatment of their disease: If the subject has stable
disease (the tumor did not grow) or there is a reduction in the size of the tumor on imaging
studies or by blood count after the T-cell infusion, the subject can receive up to six
additional doses of the T cells if they wish. After each T-cell infusion, the subject will
be monitored as described above.