A Pediatric Study of a Plerixafor Containing Regimen In Second Allogeneic Stem Cell Transplantation
|ClinicalTrials.gov Identifier: NCT01068301|
Recruitment Status : Completed
First Posted : February 12, 2010
Last Update Posted : January 1, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Chronic Myeloid Leukemia Myelodysplastic Syndrome Non-Hodgkin's Lymphoma||Drug: Plerixafor||Phase 1|
This study will determine the following objectives:
- To determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of plerixafor in combination with fludarabine, thiotepa, and melphalan as a conditioning regimen for children and young adults undergoing a second allogeneic stem cell transplant (SCT) procedure.
The study determines the secondary objectives:
- To describe the pharmacokinetic properties of plerixafor in this study population
- To estimate the cumulative incidence of relapse and overall survival in study participants at one year after this second transplant procedure
Other exploratory objectives include:
- To study the correlation between the pharmacokinetic properties of plerixafor and key regulatory and effector T cell populations in blood before and after exposure to plerixafor.
- To evaluate the content of leukemia cells in bone marrow and in blood before and after exposure to plerixafor
- To evaluate key regulatory and effector T cell populations in bone marrow and in blood before and after exposure to plerixafor
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Pediatric Study of a Plerixafor Containing Regimen In Second Allogeneic Stem Cell Transplantation|
|Study Start Date :||May 2010|
|Primary Completion Date :||October 2013|
|Study Completion Date :||October 2013|
Second Allogeneic Transplant Procedure Recipient
Participants with Acute Lymphoblastic Leukemia (ALL); Acute Myeloid Leukemia (AML); Myelodysplastic Syndrome (MDS); Chronic Myeloid Leukemia (CML); Juvenile Myelomonocytic Leukemia (JMML); Non-Hodgkin lymphoma (NHL) with evidence of bone marrow disease, receiving a second allogeneic transplant procedure.
Plerixafor in combination with fludarabine, thiotepa and melphalan as a conditioning regimen for patients undergoing a second allogeneic transplant procedure (bone marrow or peripheral blood). A traditional 3+3 phase I design will be employed during this study, where dose escalations are planned in groups of 3 participants. No intra-participant escalation will be allowed and dose escalation will not be considered until toxicity information is available from at least 3 evaluable participants at the current dose level.Plerixafor will be given intravenously (IV) rather than subcutaneously (SQ) to minimize discomfort associated with repeated daily injections (up to 3) to the pediatric population of this study.
- To determine the dose-limiting toxicity and maximum tolerated dose of plerixafor in combination with fludarabine, thiotepa and melphalan as a conditioning regimen for patients undergoing a second allogeneic transplant procedure. [ Time Frame: 7 days post transplant ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01068301
|United States, Tennessee|
|St. Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|Principal Investigator:||Ashok Srinivasan, MD||St. Jude Children's Research Hospital|