Trial Information

Transplantation With T-Cell Depleted Autologous Peripheral Stem Cells for Severe Systemic Sclerosis: A Phase I Dose Escalation Study

SSc is a chronic disease involving the abnormal growth of connective tissue, which supports
the skin and internal organs. This disease can affect the skin, making it hard and tight; it
can also damage the blood vessels and internal organs such as the heart, lungs, and kidneys.
Initially, precursor blood cells will be mobilized from the bone marrow into the blood
stream after chemotherapy and white blood cell growth factors are administered. These
precursors (or autologous stem cells) can be harvested from the bloodstream in a procedure
called leukapheresis; it is the precursor blood cells that are transplanted back into the
patient's body after high dose chemotherapy. Autologous stem cells are preferred over donor
bone marrow because there is no risk of rejection. This study will evaluate the safety and
effectiveness of self bone marrow transplants after intravenous chemotherapy in patients
with SSc.

Prior to transplantation, patients will undergo diphtheria/tetanus (DT) vaccination and
blood collection. Two weeks after vaccination, patients will have a Hickman catheter
inserted into their bodies and will be admitted to the hospital to receive mobilization
chemotherapy with intravenous (IV) cyclophosphamide. Patients will be discharged after
receiving the cyclophosphamide therapy with the understanding that they must stay locally
and must return to the outpatient clinic daily to have blood samples drawn and to receive an
injection of a growth factor, G-CSF, in stimulate blood cell production. Patients will
undergo leukapheresis at the clinic when their white blood cell (WBC) counts reach 2500
cells/mm3 or more. A machine called the Nexell Isolex 300i will be used to remove T-cells
from the cells collected by leukapheresis.

After leukapheresis and other pre-transplant procedures have been completed, patients will
be hospitalized for approximately 14 to 21 days. On Days 1 through 5 of hospitalization,
patients will receive IV fludarabine and one of several possible dose levels of
cyclophosphamide. On Days 3 through 5, patients will receive IV thymoglobulin to kill the
T-cells that cause the damage from systemic sclerosis. On Day 8, patients will receive their
own stem cells from the previous leukapheresis procedure. While in the hospital, patients
will be monitored by daily blood collection and will not be discharged until their white
blood cell counts return to a safe, stable level. Prior to discharge from the hospital,
patients will undergo a second leukapheresis.

Patients are required to stay locally in Pittsburgh up to 100 days post-transplantation.
Study visits will occur at the clinic every week for the first three months after transplant
and again at 4, 5, 6, 9, 12, 18, and 24 months post-transplantation. Study visits will
include a physical exam and blood collection; patients will be also asked to complete a
questionnaire. Patients will undergo an electrocardiogram (EKG) at Month 1, a chest x-ray at
Month 6, 24-hour urine collection at Months 6 and 18, and pulmonary tests at Months 6, 12,
and 24. Additional leukapheresis will be conducted at 12 and 24 months post-transplant to
assess patients' health.