Earlier, the patients previous bone marrow transplant donor gave the investigator blood to make CD7 CD28 chimeric receptor- T cells in the laboratory. These cells were grown and frozen for the patient. To get the CD7 antibody and CD28 to attach to the surface of the T cell, investigators will insert 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 investigators find the T cells in the patient's blood after investigators inject them. This virus also helps the investigators find the T cells in patients blood after they are injected. To ensure the T cells grow well in the lab, the investigators adds small amounts of medications that are often used to treat patients with cancer or other illnesses. These medications are washed off of the cells prior to injecting them into the patient's body. Because patients will have received cells with a new gene in them, patients will be followed for a total of 15 years to see if there are any long term side effects of gene transfer. If patients cannot visit the clinic, they may be contacted by the research coordinator or physician.
When patients enroll on this study, they will be assigned a dose of CD7 chimeric receptor-T cells. Several studies suggest that the infused T cells need room to be able to proliferate (grow) and accomplish their functions and that this may not happen if there are too many other T cells in blood. Because of that, patients will receive two chemotherapy medications prior to receiving the CD7 chimeric receptor-T cells. One medication is called cyclophosphamide and the other fludarabine. Patients will receive 3 daily doses of each drug, ending at least one day before they receive the chimeric receptor-T cells. These drugs will decrease the numbers of the patients own T cells before investigators infuse the CD7 chimeric receptor T cells and also will help decrease the number of other cells that may interfere with the chimeric receptor-T cells working well. Although investigators do not expect any effect on tumors with the doses that patients will receive, these drugs are part of many regimens that are used to treat leukemia or lymphoma. Investigators prefer that patients do not receive other chemotherapy or treatments for their cancer until 6 weeks after cell infusion but patients can do so if their doctors thinks it is medically necessary.
Patients will be given an injection of cells into the vein through an IV at the assigned dose. Before patients receive the injection, they will be given a dose of Benadryl and Tylenol. The injection will take about 1-10 minutes. Investigators will follow patients in the clinic after the injection for up to 3 hours, and they will have to remain locally for at least 4 weeks after the infusion. If patients experience any side effects (see section on risks below), they may have to be hospitalized for evaluation and management. If after a 4-6 week evaluation period the patient has achieved a complete response (measured by bone marrow or radiology scans), the patient's primary oncology doctors may decide s/he should proceed to bone marrow transplant, at which time s/he will be removed from the treatment portion of the study.
The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.
MEDICAL TESTS BEFORE TREATMENT
Before being treated, patients will receive a series of standard medical tests:
Physical exam and History Blood tests to measure blood cells, kidney and liver function Measurements of the patient's tumor by scans and/or bone marrow studies Testing of patient's blood for certain viral infections An ultrasound of patient's heart to make sure his/her heart function is appropriate for the study if the patient has not had one recently
MEDICAL TESTS DURING AND AFTER TREATMENT:
Patients will receive standard medical tests when they are getting the infusion and after:
Physical exams and History Blood tests to measure blood cells, kidney and liver function Measurements of the patient's tumor by scans and/or bone marrow studies 4-6 weeks after the infusion
To learn more about the way the CD7 chimeric receptor-T cells are working and how long they last in the body, extra blood will be drawn. The total amount on any day is about 10 teaspoons (50 mL) or no more than 3 mL per 2.2 pounds body weight in children. This volume is considered safe but may be decreased if patients are anemic. This blood may be drawn from a central line if one is available. Blood will be taken before patients start the chemotherapy a few days prior to the cell infusion. On the day patients receive the cells, blood will be taken before the cells are given and several hours afterwards. Other blood will be drawn one week after the infusion, 2 weeks, 3 weeks, 4 weeks, 6 weeks and 8 weeks after the infusion, at 3 months, at 6 months, at 9 months, at 1 year, every 6 months for 4 years, then yearly for a total of 15 years. The total blood drawn during a patient's participation in this study will not exceed 280 teaspoons.
