Stem Cell Transplant With Th2/Tc2 Cells to Treat Advanced Breast Cancer
Status:
Completed
Trial end date:
2013-08-09
Target enrollment:
Participant gender:
Summary
This Phase 1 trial will investigate the safety of a modified stem cell transplant procedure
for treating advanced breast cancer. Patients with cancers can sometimes benefit greatly from
transplants of stem cells (cells produced by the bone marrow that mature into blood cells).
In addition to producing new bone marrow and restoring normal blood production and immunity,
the donated cells fight any residual tumor cells that might have remained in the body, in
what is called a "graft-versus-tumor" effect. However, severe problems, or sometimes even
death, may follow these transplants as a result of the high-dose chemotherapy and radiation
that accompany the procedure. Also, donated immune cells called lymphocytes, or T cells,
sometimes attack healthy tissues in a reaction called graft-versus-host-disease (GVHD),
damaging organs such as the liver, intestines and skin. This study will use the following
strategies to try to reduce these risks:
- "Induction chemotherapy" to reduce patients' immunity in an attempt to prevent rejection
of the donated stem cells
- Reduced-intensity conditioning chemotherapy that is easier for the body to tolerate and
involves a shorter period of complete immune suppression
- Removal of lymphocytes from the donor stem cells for transfusion in small quantities at
monthly intervals following the stem cell transplant to reduce the risk of GVHD
- Transplant of specific lymphocytes called Th2/Tc2 cells that may increase the percentage
of donor stem cells accepted by the patient without significantly increasing GVHD
Patients between 18 and 75 years of age with advanced (stage IV) breast cancer that does not
respond to standard therapy may be eligible for this study. Candidates are screened with a
medical history, physical and dental examinations, x-ray studies and bone marrow biopsies to
evaluate disease status, blood and urine tests (including a blood test for genetic match with
the donor), and lung and heart function tests.
Participants have a central venous line (large plastic tube) placed into a major vein. This
tube stays in the body during the entire treatment period for infusing the donated stem cells
and T lymphocytes, giving medications, including chemotherapy and other drugs, antibiotics,
and blood transfusions, and withdrawing blood samples. Treatment starts with induction
chemotherapy, in which patients receive one or two cycles of the anti-cancer drugs
fludarabine and cyclophosphamide. (One cycle consists of 4 days on drug therapy followed by a
17-day rest period.) G-CSF, a drug that boosts white cell production, is also given to reduce
the risk of infection. Several days before the transplant procedure, patients begin
conditioning chemotherapy with higher doses of cyclophosphamide and fludarabine. Three days
after the conditioning therapy is completed, the stem cells are infused. To help prevent both
rejection of the donor stem cells and GVHD, patients receive cyclosporine (first by vein and
later by mouth) for several weeks after the transplant. Infusions of donor lymphocytes begin
about 6 weeks after the transplant to boost the immune system and enhance the
graft-versus-tumor effect.
Patients may leave the hospital when they are able to eat and drink, have no fever or
infection, and have a normal or near-normal white cell count. They return for follow-up
visits twice a week for the first 100 days after the transplant, then every 3 months, then 6
months and then yearly for at least 5 years post-transplant. The visits include a medical
history, physical examination, and blood draws, as well as disease staging with CT scans
every month for the first 6 months.