Phase I/II Study of Myeloablative Allogeneic Stem Cell Transplantation for Aggressive Hematologic Malignancies Using Clofarabine and Busulfan x 4 (Clo/BU4) Regimen
Transplants with stem cells collected from the blood of an unrelated donor (allo-HSCT) are
being used more commonly for many blood cancers which are not curable with more conventional
methods of chemotherapy. Although allo-HSCT has great potential, there are still high risks
due to infections, graft-versus-host disease (GVHD), where the donor's cells attack the
recipient's tissues as foreign, and due to toxic effects of the chemotherapy drugs given to
prepare (or condition) the recipient's bone marrow for transplant.
As a reduced intensity conditioning, a combination of Fludarabine and a lower dose of
Busulfan (Flu/BU2) is one of the most popular regimens. Among full-intensity regimens, a
combination of Fludarabine and standard-dose Busulfan (Flu/BU4) has been investigated
recently and shown to be very well tolerated.
Clofarabine, similar to Fludarabine, is known to have a stronger anti-tumor effect than
Fludarabine and has shown promise in treating aggressive acute leukemias. In addition,
evidence is that it is well-tolerated with manageable side effects especially in older
subjects. Thus replacing Fludarabine with Clofarabine in a full-intensity transplant
regimen, Clo/BU4 may provide a regimen with increased anti-tumor activity without adding
significant risks of toxicity.
The goals of the study are (Phase I) to determine the appropriate dose for Clofarabine with
Busulfan as a full-intensity regimen (Clo/BU4) and then (Phase II) to investigate the safety
and effectiveness of this regimen as a conditioning for HSCT in the treatment for aggressive
hematologic malignancies, in subjects where more conventional approaches are failing.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention
To establish the toxicity profile of three doses of Clofarabine in combination with Busulfan and assess the one-year overall survival rate for subjects receiving the dose of Clofarabine with a DLT rate closest to 20%.
John Magenau, M.D.
University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program
United States: Institutional Review Board
|University of Michigan, Department of Internal Medicine, Blood and Marrow Transplant Program||Ann Arbor, Michigan 48170|