This phase I/II clinical trial will test the safety and the efficacy of post transplant administration of plerixafor in enhancing hematological recovery in humans. Patients who are appropriate candidates for myeloablative allogeneic stem cell transplantation from an HLA-matched sibling, matched unrelated donor or umbilical cord blood are eligible for enrollment. The investigators plan to enroll a total of 50 patients for this study (30 patients with HLA-matched sibling or matched unrelated donor transplant, and 20 patients with umbilical cord blood transplant). During phase I study, a small number of patients (3-6 patients from each group) will be enrolled to determine the safety of post transplant administration of plerixafor. Patients will receive plerixafor given at 240 µg/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment. Limiting toxicities are defined as primary or secondary graft failure, plerixafor-related severe premature ventricular arrhythmia or death. If safety criteria are met from the investigators phase I study, the investigators will proceed with phase II study to determine the efficacy of post transplant administration of plerixafor in enhancing haematological recovery. The experimental aspect of this study is the use of plerixafor and all other aspects of care will be in line with the standard of care. Both Phase I and Phase II patients will be combined for efficacy analysis, and data collected from this study will be compared with the investigators historical control. The results from this study will set the stage and provide the justification for a larger phase 3 trial.
Recruitment to this trial will be stratified by donor type as HLA (human leukocyte antigen) matched sibling, matched unrelated donor or umbilical cord blood. Patients will be conditioned with a myeloablative regimen such as, but not limited to, total body irradiation and cyclophosphamide. The donor stem cell grafts will come from mobilized peripheral blood of 8/8 or 7/8 HLA-identical family members, 8/8 (HLA A, B, C, DRBeta1) allele-level matched unrelated donors, or dual umbilical cord blood grafts with at least 4 of 6 HLA matching at HLA A and B (low resolution) and DRBeta1 (at high resolution). The target CD34+ cell dose will be 5 X 10(6)/kg recipient ideal body weight. For HLA matched sibling or matched unrelated donor (MUD) transplants, all patients will receive a minimum of 2 X 10(6) CD 24+ cells/kg. For cord blood transplants, each unit will contain a minimum total nucleated cell count of of 1.5 X 10(7)/kg. Post-transplant GVHD (graft versus host disease) prophylaxis will be given per institutional standard.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
41
Matched sibling or Dual Cord donor subjects will receive plerixafor at 240 ug/kg subcutaneously every other day beginning at day +2 after transplant until day +21 or engraftment occurs.
Duke University Medical Center
Durham, North Carolina, United States
Medical University of South Carolina
Charleston, South Carolina, United States
Time to Neutrophil Recovery
leukocytes \> 500/ul on 2 consecutive days
Time frame: 100 Days post Transplant
Time to Platelet Recovery
platelet \> 20,000/ul on 2 consecutive days
Time frame: 100 Days Post Transplant
Plerixafor-associated Adverse Events
Time frame: 100 Days Post Transplant
Transplant-related Mortality
Time frame: 100 Days Post Transplant
Absolute Lymphocyte Count at Day 90
Cell reconstitution - absolute lymphocyte count at day 90 post transplant.
Time frame: 90 days
IL-12 at Day 30
IL-12 at day 30; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.
Time frame: 30 days
Participants Experiencing Grade II-IV Acute Graft Versus Host Disease
We are reporting on the number of participants experiencing a grade II-IV acute graft versus host disease will be assessed weekly through Day 100 post transplant. Staging and grading of Acute GvHD is graded by pattern of organ involvement and clinical performance status using the Grading Index of Acute GvHD (Gluckman) and the Grading Index of Acute GVHD by the CIBMTR (Centers for International Blood and Marrow Transplant Research)
Time frame: 100 days
CD3+ Cell Count at Day 90
Cell reconstitution - CD3+ cell count at day 90 post transplant. This is a marker for the function of your immune system.
Time frame: 90 Days
CD4 Cell Count at Day 90
CD4 cell count at Day 90; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.
Time frame: 90 days
CD8 Cell Count at Day 90
CD8 cell count at Day 90; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).
Time frame: 90 days
NK Cell Count at Day 90
NK cell count at Day 90;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.
Time frame: 90 days
B Cell Count at Day 90
B cell count at Day 90; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.
Time frame: 90 days
IFN Gamma at Day 30
IFN gamma at day 30; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.
Time frame: 30 days
TNF-alpha at Day 30
TNF-alpha at day 30; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.
Time frame: 30 days
CD4 Cell Count at Day 30
CD4 cell count at Day 30; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.
Time frame: 30 days
CD4 Cell Count at Day 60
CD4 cell count at Day 60; CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells.
Time frame: 60 days
CD8 Cell Count at Day 30
CD8 cell count at Day 30; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).
Time frame: 30 days
CD8 Cell Count at Day 60
CD8 cell count at Day 60; CD8 (cluster of differentiation 8) is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor (TCR).
Time frame: 60 days
NK Cell Count at Day 30
NK cell count at Day 30;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.
Time frame: 30 days
NK Cell Count at Day 60
NK cell count at Day 60;Natural killer cells or NK cells are a type of cytotoxic lymphocyte critical to the immune system.
Time frame: 60 days
B Cell Count at Day 30
B cell count at Day 30; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.
Time frame: 30 days
B Cell Count at Day 60
B cell count at Day 60; B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype and they function as part of the immune system.
Time frame: 60 days
IL-12 at Day 7
IL-12 at day 7; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.
Time frame: 7 days
IL-12 at Day 14
IL-12 at day 14; Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation.
Time frame: 14 days
IFN Gamma at Day 7
IFN gamma at day 7; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.
Time frame: 7 days
IFN Gamma at Day 14
IFN gamma at day 14; Interferon gamma (IFNγ) is a dimerized soluble cytokine that is the only member of the type II class of interferons which are important for immunity against infection.
Time frame: 14 days
TNF-alpha at Day 7
TNF-alpha at day 7; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.
Time frame: 7 days
TNF-alpha at Day 14
TNF-alpha at day 14; Tumor necrosis factor is a cell signaling protein (cytokine) involved in systemic inflammation and is one of the cytokines that make up the acute phase reaction. The primary role of TNF is in the regulation of immune cells.
Time frame: 14 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.