CTLs Expressing CD19 Chimeric Receptors, CD19 Positive Malignancies Post SCT, MULTIPRAT

• Evaluate safety/persistence of escalating doses of allogeneic CMV, EBV and Adenovirus specific CTLs modified to express artificial T-cell receptors targeting CD19 molecule given for prophylaxis, persistence or relapse of high risk B-cell ALL post HSCT [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  

• To evaluate the effects of gene modified CTL on measurable disease. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  
• To evaluate the impact of the gene modified CTL on virus-specific T-lymphocyte immune reconstitution. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  
• To evaluate the impact of the gene modified CTL on normal CD19+ B-cell immune reconstitution post-HSCT. [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  

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.