A Phase II Study of High-Dose Immunosuppressive Therapy (HDIT) Using Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) and Thymoglobulin, and Autologous CD34+ Hematopoietic Stem Cell Transplant (HCT) for the Treatment of Poor Prognosis Multiple Sclerosis
MS is a chronic autoimmune disease of the central nervous system in which myelin, the
protective coat that surrounds nerve cells, is damaged or destroyed by autoimmune T cells
and macrophages, leading to an eventual loss of neurologic function. In a pilot study in
Europe using high-dose chemotherapy, it was observed that 18 of 19 MS patients stabilized or
improved clinically, and only one patient showed a new lesion on magnetic resonance imaging
(MRI) of the brain at 4.5 years after treatment. Improvement was seen in quality-of-life
assessments.
In ITN033AI, high-dose chemotherapy with autologous CD34-selected hematopoietic cell
transplantation will be given to confirm the results from the pilot study and to offer
therapy to patients with early MS and a poor prognosis. Research studies will be performed
in addition to clinical assessments to better understand the effect of the treatment on the
activity of MS. High-dose chemotherapy will be used to deplete autoreactive immune cells.
These regimens also deplete the bone marrow, the source of blood-forming CD34+ stem cells
which causes very low blood counts. Therefore, the participant's autologous CD34+
hematopoietic stem cells will be collected before high dose immunosuppressive therapy is
given and then returned as a transplant post-chemotherapy. Patients will be followed closely
after the autologous transplantation since they will be at risk for infections after
treatment.
At the beginning of the study, participants will undergo a number of screening and baseline
procedures, including a physical exam, blood collection, MS-confirming neurology exams and
questionnaires, and MRI procedures. Participants will be given prednisone and
granulocyte-colony stimulating factor (G-CSF) to mobilize CD34+ hematopoietic stem cells
from the bone marrow into the peripheral blood. When the peripheral blood CD34+ cell count
reaches 20,000 cells/ml or greater, these cells will be collected by leukapheresis. In this
process, a catheter is placed into a large blood vessel, peripheral blood is withdrawn, and
a high speed sedimentation (leukapheresis) device is used to separate and retain the cells
required for autologous transplantation. Other blood cells are then returned to the
participant's body. In the laboratory, the CD34+ hematopoietic stem cell graft will be
selected and prepared from the leukapheresis collection, and stored until needed for
transplant. Seven or more days following the collection of their autologous graft,
participants will be hospitalized and receive high-dose chemotherapy consisting of
carmustine, etoposide, cytarabine, and melphalan (BEAM) and thymoglobulin. This is followed
by transplantation of the autologous hematopoietic cell graft. Participants will remain in
the hospital for observation during recovery of their peripheral blood cell counts, as
described in the protocol. Participants will receive G-CSF and blood transfusions, if
needed, and will be monitored for infections. Following discharge from the hospital, eight
study visits will occur over sixty months (five years). During these visits, participants
will undergo blood and urine collection, MRI studies, leukapheresis, and MS neurology exams
and will complete questionnaires.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Time to treatment failure
During the 5 years after transplant
No
Richard A. Nash, MD
Study Chair
Blood and Marrow Transplant Program, Colorado Blood Cancer Institute, Presbyterian/St. Luke's Medical Center, Denver
United States: Food and Drug Administration
DAIT ITN033AI
NCT00288626
July 2006
September 2015
Name | Location |
---|---|
Baylor College of Medicine | Houston, Texas 77030 |
Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
Ohio State University School of Medicine | Columbus, Ohio 43210 |
M.D. Anderson Cancer Center; Transplant site, please contact Baylor College of Medicine | Houston, Texas 77230-1402 |