A Pediatric Study of a Plerixafor Containing Regimen In Second Allogeneic Stem Cell Transplantation
Status:
Completed
Trial end date:
2013-10-01
Target enrollment:
Participant gender:
Summary
Patients with refractory hematologic malignancies, including those who develop recurrent
disease after allogeneic hematopoietic stem cell transplantation (HSCT) have a dismal
prognosis. Historically, both regimen-related mortality and disease recurrence have been
significant causes of treatment failure in this heavily pre-treated patient population. Novel
therapeutic agents that target molecular signaling mechanisms and increase the sensitivity of
leukemic cells to apoptosis may clearly play a role in this setting.
This study hypothesizes that interrupting the SDF-1/CXCR4 axis using the selective CXCR4
antagonist plerixafor may be useful as a leukemic stem cell mobilizing agent for patients who
are refractory to standard dose chemotherapy and in relapse after an allogeneic transplant.
This hypothesis is based on the dependence of leukemia cells on MSCs for survival signals as
described above and on the preclinical data that suggest increased efficacy by antileukemia
agents when leukemia cells are separated from MSCs.
In the present trial, the study proposes to add plerixafor to enhance the conditioning
regimen cytotoxicity. At this time the goal is to determine the maximum tolerated dose (MTD)
of plerixafor through the process of dose limiting toxicity (DLT) evaluation. Pharmacokinetic
studies will be conducted. Additional studies will quantify and the content of leukemia cells
and key regulatory and effector T cell populations in the bone marrow and blood before and
after exposure to this medication.
If the observed outcomes of this trial are promising, it could serve as a platform on which
to study further use of plerixafor as a complimentary agent with conditioning as well as
other chemotherapeutic regimens for patients with relapsed or refractory hematologic
malignancies.