Anti-Third Party T Lymphocytes With Nonmyeloablative Stem Cell Transplantation for Treatment of Indolent Lymphoid Malignancies
GVHD can be a major problem after stem cell transplantation from a healthy donor. It is
caused by T-lymphocytes (a type of immune cell) from the donor that can react badly against
the person receiving the transplant (the recipient). Researchers want to see if stimulating
the donor T-lymphocytes against another person (a third party) and growing them for 28 days
will decrease the chance of developing GVHD.
If you are found to be eligible to take part in this study, you will receive the below
treatment, including chemotherapy and radiation, before your stem cell transplantation.
These include rituximab, cyclophosphamide, fludarabine, and mesna. Rituximab is designed to
attach to lymphoma cells, causing them to die. Cyclophosphamide is designed to destroy
cancer cells by interfering with their multiplication and slowing or stopping their growth
and spread throughout the body. Fludarabine is designed to interfere with DNA repair
enzymes so that the leukemic cell cannot repair damaged DNA. This increases the likelihood
of the cell dying. Mesna is a drug that lowers the risk of bladder side effects by the
cyclophosphamide. Total body radiation is given to to reduce the risk of transplant
Participants with CLL or lymphoma will receive Rituxan (rituximab) by vein, given over
several hours for each dose. The first rituximab dose is 13 days before the transplant.
This will be followed by 3 more doses of rituximab, given 6 days before the transplant, and
1 and 8 days after the transplant. All participants will receive fludarabine by vein over
30 minutes once per day for 4 days, starting 6 days before the transplant. All participants
will also receive cyclophosphamide by vein over 2 hours. The cyclophosphamide will be given
immediately after the first dose of fludarabine. All participants will also receive a
continuous infusion of mesna by vein for 24 hours after receiving the cyclophosphamide. One
day before transplantation, you will have total body radiation.
After receiving total body radiation, you will receive your stem cell transplantation. On
the day of the transplant, you will receive the anti-third party T Lymphocytes (CTLs) by
vein. This will be followed by vein infusion of stem cells from the donor. A sample of the
anti-third party T-cells cells will also be tested for immune function.
All participants will receive sirolimus by mouth for 10 days, starting 2 days before
transplantation. Sirolimus is an immunosuppressive drug which is given to reduce the risk
of transplant rejection. You will remain in the hospital for about 4 weeks after the
transplant. You will then continue as an outpatient in the Houston area for 100 days after
your transplantation, or until your doctor feels it is okay for you to leave the Houston
If your disease gets worse after your transplantation, you may receive additional immune
cells from the donor (DLI-donor lymphocyte infusion).You may be taken off this study if the
transplant does not grow or is rejected, if not enough of the CTLs can be produced, if your
disease continues to get worse after receiving additional donors cells, or if you experience
any intolerable side effects.
You will have frequent blood tests as medically necessary to evaluate your medical
condition. About 3 tablespoons of blood will be collected for immune function testing at 1,
2, 3, 6 and 12 months after the transplant. You will have a bone marrow biopsy, x-rays, and
CT scans for evaluation of the cancer at 1, 3, 6, 9, and 12 months after the transplant.
The study is over after 1 year. You will be followed-up after that time for routine care,
as the doctors feels it is necessary.
This is an investigational study. All of the drugs used in this study, have been approved
by the FDA in the treatment of cancer and transplantation. The Miltenyi CliniMACS System
which is used to purify stem cells and the anti-third party CTLs has not been approved by
the FDA, and its use in this study is experimental. Up to 24 patients will take part in this
study. All will be enrolled at M. D. Anderson.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Number of Participants achieving engraftment without severe Graft-versus-host disease (GVHD)
Number of participants who achieve engraftment without severe GVHD at 90 days after allogeneic transplantation of CD34+ hematopoietic progenitor cells. Engraftment recorded as first day of three (3) consecutive days that the Absolute neutrophil count (ANC) exceeds 0.5 * 109/L. Graft failure is defined as failure to reach an ANC > 0.5 * 109/L within 28 days after transplantation with detectable donor cells on chimerism analysis.
Baseline to 90 days
Richard E. Champlin, MD
M.D. Anderson Cancer Center
United States: Food and Drug Administration
|U.T.M.D. Anderson Cancer Center||Houston, Texas 77030|